Obesity
Conditions
Keywords
metformin, diabetes, obesity, liraglutide
Brief summary
This study is the first administration of GSK2890457 in humans. The study will be conducted in 3 parts: - Part A (conducted at a single investigative site) will determine the safety and tolerability of GSK2890457 alone in healthy subjects during six weeks of dosing, as well as evaluating the potential for a pharmacokinetic interaction with metformin. Part A consists of Screening, Treatment (6 weeks) and Follow-up periods. - Part B (conducted at multiple sites) will determine safety, tolerability, and pharmacodynamics (PD) in subjects with Type 2 diabetes (T2D) when co-dosed for six weeks with liraglutide (Victoza). Part B consists of Screening, Run-in (1 week), Stabilization (12 weeks), Treatment (6 weeks) and Follow-up periods. - Part C (conducted at multiple sites) will determine safety, tolerability, and PD in subjects with T2D when co-dosed for 6 weeks with metformin. Part C consists of Screening, Run-in (1 week), Stabilization (12 weeks), Treatment (6 weeks) and Follow-up periods.
Interventions
DRUGGSK2890457
Provided as powder and capsule.
DRUGMetformin
Tablet Part A: Single doses on Day 1 and Day 42 orally Part B: Subject continues usual metformin dose through Run-in, and resumes after Treatment Period completed Part C: Subject continues usual metformin dose throughout study
DRUGPlacebo
Provided as powder and Capsule.
DRUGLiraglutide
Provided as Injection. 6mg/mL, 3mL injector pen that permits doses of 0.6mg, 1.2mg, and 1.8mg Subcutaneous injection 18 weeks dosing (Stabilization and Treatment Periods, Part B only
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Part A (Healthy Subjects) * Subject able to understand and voluntarily provide the consent to participate in the study * 18 - 70 years of age, inclusive, at the time of signing the informed consent and Body Mass Index (BMI) between 18.0 and 35.0 Kilogram (kg) per m\^2, inclusive * Understands and is willing, able and likely to be compliant with taking study drug and comply with all study procedures and restrictions * Subject is willing to consume the foods that are part of the standardized breakfast, lunch, and dinner * In good general health with no clinically significant and relevant abnormalities of medical history or physical examination which includes adequate renal function, alanine transaminase (ALT), alkaline phosphatase and bilirubin \<=1.5x Upper Limit of Normal (ULN ) * QTcF \< 450 millisecond (msec); or QTcF \< 480msec for subjects with right Bundle Branch Block * Females must be post-menopausal * Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment * Females who are \> 3 months postpartum and who have undergone a surgical sterilization procedure are eligible to participate in consultation with the GSK Medical Monitor Parts B and C (Type 2 Diabetic Subjects) * All the criteria mentioned in Part A except Body Mass Index (BMI) should be between 30.0 and 42.0 kg per m\^2 * Diagnosis of T2D for at least 3 months, as defined by the American Diabetes Association * All T2D subjects must meet label recommendations for metformin * For Part B, subjects must be willing to discontinue metformin and replace it with daily liraglutide administered by subcutaneous injection and they must meet label recommendations * No personal history or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
Exclusion criteria
* History of gastrointestinal disease, current or chronic history of liver disease, history of serious, severe or unstable physical or psychiatric illness , significant cardiovascular disease, surgery for weight loss or gastrointestinal surgery within 3 months of screening, any documented or reported eating disorder, uncontrolled hypertension, as evidenced by systolic pressure\>160 or diastolic pressure \>90 mmHg * Positive test for HIV, Hepatitis B, or Hepatitis C at Screening * Subjects with significant ECG abnormalities * For subjects in Part C (continuing metformin), history of untreated pernicious anemia or who have laboratory parameters suggestive of subclinical megaloblastic anemia * Presence of or symptoms of an active infection * Uncorrected Thyroid Dysfunction * History of chronic or acute pancreatitis * Currently dieting to lose weight including, but not limited to, participation in a program designed to alter body weight within the last 60 days and unwilling to maintain relatively consistent exercise patterns throughout the study * Current or recent history (within one year of screening) of alcohol or other substance abuse * Unable to refrain from the use of non-prescription drugs * Current participation in another clinical study or participation in a clinical study involving an investigational drug within 30 days of the screening visit * History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy * An employee of the sponsor or the study site or members of their immediate family.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Follow-up (Day 56) | The assessments were done at Day -1, Day 7, Day 14, Day 28, Day 42 and Follow-up Visit. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline (Day 7, 14, 28, 42 and Follow-up visit) values. |
| Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Baseline (Day -2) up to Day 41 | The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day -2. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14, 28 and 41) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Baseline (Day -1 and Day 1) up to Day 42 | During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values. |
| Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) and Day 42 | Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean. |
| Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Baseline (Day -1 and Day 1) up to Day 42 | During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. Percent change was calculated by multiplying the change from Baseline value with 100. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values. |
| Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) and Day 42 | AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean glucose AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast. Adjusted mean is reported as least square (LS) mean. |
| Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) and Day 42 of Part B and C | Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean. |
| Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) and Day 42 | Two fasting samples 5 minutes apart were taken for insulin. Baseline insulin level was the average of the 2 fasting samples. For insulin weighted mean AUC (0-4 hour) and weighted mean AUC (0-24 hour) was calculated for Baseline (Day -1) and end of treatment (Day 42). AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean insulin AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast. |
| Change From Baseline in Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR]) During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) and Day 42 | HOMA-IR was calculated from the Day -1 and Day 42 fasting glucose and insulin values using dataset generated from the HOMA-2 model. It contained the estimates for HOMA-% insulin sensitivity (S) for pairs of fasting glucose and fasting insulin values. Study data was merged with the HOMA dataset by glucose and insulin. HOMA-IR was calculated as 100/HOMA-%S. HOMA-IR was not determined for any values outside the ranges of plasma glucose 3.5 to 25.0 mmol/L (63 - 450 mg/dL) and plasma insulin 20 to 400 pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points. |
| Change From Baseline in Matsuda Index During the Double Blind-treatment Period of Part B and C | Baseline (Day -1) and Day 42 | The matsuda index was calculated from the Day -1 and Day 42 glucose and insulin results as 10,000 divided by (fasting plasma glucose x fasting plasma insulin x mean glucose at 0-2 hour post-dose x mean insulin at 0-2 hour post dose)\^1/2, where glucose was measured in mmol/L and insulin in pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points. |
| Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A | Up to Follow-up (8 weeks) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5. |
| Number of Participants With Any AE, SAE or Death During Part B and Part C | Up to Follow-up (8 weeks) | An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as ALT \>=3 x ULN, and total bilirubin \>=2 x ULN or international normalized ratio \>1.5. |
| Number of Participants With Any Hypoglycemic Events During Part A | Up to Follow-up (8 weeks) | Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of complete blood count (CBG) or plasma glucose value of \<50 milligram per deciliter (mg/dL) for Part A or \<70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values \<70 mg/dL as a physiological response to altered food intake (e.g., fasting). |
| Number of Participants With Any Hypoglycemic Events During Part B and Part C | Up to Follow-up (8 weeks) | Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of CBG or plasma glucose value of \<50 mg/dL for Part A or \<70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values \<70 mg/dL as a physiological response to altered food intake (e.g., fasting). |
| Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at on Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study | Baseline (Day -1) and Day 42 | The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) and Day 42 | The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) and Day 42 | The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Up to Day 42 | The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as rare, trace, +1, 2+, RBC's and WBC's as \<1, 1, 2, 3 and 4. Protein concentration ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. Trace was the highest concentration for occult blood. Bacteria concentration ranged from rare to moderate, where rare indicated lowest concentration and moderate indicated highest concentration. Ketones ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. RBC and WBC ranged from \<1 to 4, where \<1 indicated lowest concentration and 4 indicated highest concentration. Highest concentration indicated worse outcome. |
| Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as few, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, and 20-40. Few was the highest concentration of bacteria. Occult blood ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Epithelial cell ranged from 0-5 to 10-20, 0-5 indicated lowest and 10-20 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-5 was highest concentration for hyaline casts. Ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. RBC and WBC ranged from 0-3 to 20-40, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome. |
| Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Up to Day 42 | The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. The participants were categorized as few, many, moderate, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, 20-40, 40-60. Protein and ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Bacteria and uric acid crystals ranged from few to moderate, few indicated lowest and moderate indicated highest concentration. Trace was the highest concentration of occult blood. Epithelial cells ranged from 0-5 to \>10, 0-5 indicated lowest and \>10 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-1 was highest concentration for hyaline casts. RBC and WBC ranged from 0-3 to 40-60, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome. |
| Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Up to Day 42 | Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Da y 1, Day 7, Day 14, Day 28 and Day 42. |
| Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Up to Day 42 | Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. |
| Mean pH Values of Urine During the Double-blind Treatment Period of Part A | up to Day 42 | Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day 1, Day 7, Day 14, Day 28 and Day 42. |
| Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Up to Day 42 | Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day -1, Day 7, Day 14, Day 28 and Day 42. |
| Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Baseline (Day -1) up to Day 42 | Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | Baseline (Day 1, Randomization) up to Follow-up (Day 56) | Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QT duration corrected for HR by Fridericia's formula (QTcF) and QT duration corrected for HR by Bazett's formula (QTcB intervals. The assessments were done at Day 1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in ECG Intervals During Part B and C | Baseline (Day -1) up to Follow-up (Day 56) | Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QTcB, QTcF and RR intervals. The assessments were done at Day -1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
| Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A | Baseline (Day 1, Randomization) up to Day 42 | The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14 and 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose | Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The first occurrence of the Cmax was determined directly from the raw concentration-time data. |
| Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose | Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The time at which Cmax was observed was determined directly from the raw concentration-time data. |
| AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A | Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose | Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The AUC (0-10 hour) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The analysis population included Metformin PK Population in Part A comprising of all participants in All Subjects Population for whom a PK sample was obtained and analyzed for metformin. |
| Cmax of Metformin During the Double-blind Treatment Period of Part A | Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose | Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The first occurrence of the Cmax was determined directly from the raw concentration-time data. |
| Tmax of Metformin During the Double-blind Treatment Period of Part A | Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose | Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The time at which Cmax was observed was determined directly from the raw concentration-time data. |
| AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Metformin During the Double-blind Treatment Period of Part C | Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose | Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The AUC 0-t was planned to be determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen. |
| Cmax of Metformin During the Double-blind Treatment Period of Part C | Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose | Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The first occurrence of the Cmax was planned to be determined directly from the raw concentration-time data. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen. |
| Tmax of Metformin During the Double-blind Treatment Period of Part C | Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose | Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The time at which Cmax was observed was planned to be determined directly from the raw concentration-time data. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen. |
| Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose | Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post dose. The AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The analysis population included Liraglutide Pharmacokinetic (PK) Population in Part B comprising of all participants in All Subjects Population for whom a PK sample was obtained and analyzed for Liraglutide. |
Countries
United States
Participant flow
Recruitment details
The study was conducted in 3 parts in healthy male and female participants aged 18 to 70 years in Part A and in participants with type 2 diabetes (T2D) in Part B and C across three centers of United States of America.
Pre-assignment details
A total of 15 participants were randomized in Part A, 20 were randomized in Part B and 18 were randomized in Part C.
Participants by arm
| Arm | Count |
|---|---|
| Part A-Placebo Healthy participants received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, matching placebo to GSK2890457 was given in the evening. | 4 |
| Part A-GSK2890457 Healthy participants received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. On Day 1 and 42, after overnight fasting, participants received 500 mg IR tablet of metformin just before breakfast. On Day 1 (5 g) and Day 42, GSK2890457 was given in the evening. | 11 |
| Part B-Placebo+Liraglutide Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 milligram (mg) once daily by subcutaneous injection during the Treatment period along with placebo. | 6 |
| Part B-GSK2890457+Liraglutide Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants received liraglutide up to 1.8 mg once daily by subcutaneous injection during the Treatment period along with GSK2890457. | 14 |
| Part C-Placebo+Metformin Participants with T2D, received oral dose of matching placebo to GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5 g placebo kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. Participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2, dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with placebo, taken one hour prior to placebo as once daily or BID. | 6 |
| Part C-GSK2890457+Metformin Participants with T2D, received oral dose of GSK2890457 as units of 5 g kit BID for 6 weeks. Each unit of 5g kit contained 3 sachets of powder and a bottle containing 3 capsules. The powder was mixed with 12 ounces of flavored water, capsules were taken with 120-240 mL of water. The participants were titrated up from 15 g to 40 g over a 7 day period, if tolerated. On Day 2 the dose was 15 g, taken 5 g (1 unit) in morning and 10 g (2 unit) in evening. On Day 4, 15 g (3 unit doses) in morning and 15 g (3 unit doses) in evening. On Day 7, 20 g (4 unit doses) in morning and 20 g (4 unit doses) in evening. Participants continued their usual dose of metformin during the treatment period along with GSK2890457, taken one hour prior to GSK2890457 as once daily or BID. | 12 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Part A-Placebo | Total | Part C-GSK2890457+Metformin | Part C-Placebo+Metformin | Part B-GSK2890457+Liraglutide | Part B-Placebo+Liraglutide | Part A-GSK2890457 |
|---|---|---|---|---|---|---|---|
| Age, Customized 18 to 70 years | 4 Participants | 53 Participants | 12 Participants | 6 Participants | 14 Participants | 6 Participants | 11 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 11 Participants | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 42 Participants | 10 Participants | 6 Participants | 13 Participants | 5 Participants | 5 Participants |
| Sex: Female, Male Female | 1 Participants | 15 Participants | 4 Participants | 3 Participants | 3 Participants | 3 Participants | 1 Participants |
| Sex: Female, Male Male | 3 Participants | 38 Participants | 8 Participants | 3 Participants | 11 Participants | 3 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 11 | 0 / 6 | 0 / 14 | 0 / 6 | 0 / 12 |
| other Total, other adverse events | 3 / 4 | 10 / 11 | 1 / 6 | 3 / 14 | 3 / 6 | 3 / 12 |
| serious Total, serious adverse events | 0 / 4 | 0 / 11 | 0 / 6 | 0 / 14 | 0 / 6 | 0 / 12 |
Outcome results
Primary
Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) and Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C | -0.018 Ratio | Standard Deviation 0.011 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C | -0.009 Ratio | Standard Deviation 0.0164 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C | 0.002 Ratio | Standard Deviation 0.0126 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameter of Triiodothyronine (T3) Uptake During the Double-blind Treatment Period of Part B and C | -0.001 Ratio | Standard Deviation 0.0173 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Albumin, Day 7 | 0.0 g/L | Standard Deviation 2.45 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Albumin, Day 14 | 2.0 g/L | Standard Deviation 1.83 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Albumin, Day 28 | 2.5 g/L | Standard Deviation 2.89 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Albumin, Day 42 | 2.5 g/L | Standard Deviation 2.08 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Total protein, Day 7 | -0.8 g/L | Standard Deviation 3.77 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Total protein, Day 14 | -0.3 g/L | Standard Deviation 2.06 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Total protein, Day 28 | 1.0 g/L | Standard Deviation 2.45 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Total protein, Day 42 | 0.8 g/L | Standard Deviation 2.06 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Total protein, Day 42 | -3.1 g/L | Standard Deviation 4.25 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Albumin, Day 7 | -0.3 g/L | Standard Deviation 1.9 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Total protein, Day 7 | -2.1 g/L | Standard Deviation 3.24 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Albumin, Day 14 | 0.4 g/L | Standard Deviation 1.96 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Total protein, Day 28 | -2.2 g/L | Standard Deviation 2.74 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Albumin, Day 28 | 0.4 g/L | Standard Deviation 1.07 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Total protein, Day 14 | -1.2 g/L | Standard Deviation 4 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part A | Albumin, Day 42 | 0.0 g/L | Standard Deviation 2.36 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 7 | 2.0 g/L | Standard Deviation 2 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 14 | 2.7 g/L | Standard Deviation 3.01 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 28 | 1.8 g/L | Standard Deviation 1.94 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 42 | 0.0 g/L | Standard Deviation 1.9 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 7 | 3.0 g/L | Standard Deviation 3.03 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 14 | 4.0 g/L | Standard Deviation 5.1 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 28 | 3.2 g/L | Standard Deviation 4.17 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 42 | 0.5 g/L | Standard Deviation 1.38 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 14 | 2.7 g/L | Standard Deviation 3.67 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 7 | 2.9 g/L | Standard Deviation 2.51 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 14 | 2.6 g/L | Standard Deviation 2.17 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 42 | -0.6 g/L | Standard Deviation 2.79 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 28 | 3.2 g/L | Standard Deviation 3.65 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 42 | 0.4 g/L | Standard Deviation 2.02 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 28 | 2.8 g/L | Standard Deviation 2.54 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 7 | 3.1 g/L | Standard Deviation 2.11 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 28 | 2.8 g/L | Standard Deviation 4.17 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 28 | 2.3 g/L | Standard Deviation 1.97 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 42 | -0.8 g/L | Standard Deviation 1.94 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 7 | 1.0 g/L | Standard Deviation 4.15 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 14 | 1.7 g/L | Standard Deviation 4.72 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 42 | -0.7 g/L | Standard Deviation 3.08 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 7 | 1.3 g/L | Standard Deviation 2.07 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 14 | 0.8 g/L | Standard Deviation 2.79 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 28 | 1.9 g/L | Standard Deviation 2.71 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 42 | -1.3 g/L | Standard Deviation 2.23 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 14 | 1.6 g/L | Standard Deviation 3.15 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Albumin, Day 7 | 0.5 g/L | Standard Deviation 1.88 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 7 | 1.1 g/L | Standard Deviation 3.12 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 42 | -1.5 g/L | Standard Deviation 3.45 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 28 | 3.1 g/L | Standard Deviation 4.03 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Albumin and Total Protein During the Double-blind Treatment Period of Part B and C | Total protein, Day 14 | 2.2 g/L | Standard Deviation 4.41 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALP, Day 7 | -6.0 International unit per liter (IU/L) | Standard Deviation 5.83 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALP, Day 14 | -1.3 International unit per liter (IU/L) | Standard Deviation 6.08 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALP, Day 28 | 0.0 International unit per liter (IU/L) | Standard Deviation 4.83 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALP, Day 42 | -1.0 International unit per liter (IU/L) | Standard Deviation 3.37 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALT, Day 7 | 5.5 International unit per liter (IU/L) | Standard Deviation 10.15 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALT, Day 14 | 1.3 International unit per liter (IU/L) | Standard Deviation 2.99 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALT, Day 28 | 2.0 International unit per liter (IU/L) | Standard Deviation 5.48 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALT, Day 42 | 5.3 International unit per liter (IU/L) | Standard Deviation 17.37 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | AST, Day 7 | 2.3 International unit per liter (IU/L) | Standard Deviation 2.06 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | AST, Day 14 | -2.3 International unit per liter (IU/L) | Standard Deviation 3.4 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | AST, Day 28 | -0.8 International unit per liter (IU/L) | Standard Deviation 3.1 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | AST, Day 42 | 2.3 International unit per liter (IU/L) | Standard Deviation 6.95 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | GGT, Day 7 | 1.5 International unit per liter (IU/L) | Standard Deviation 5.45 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | GGT, Day 14 | 1.0 International unit per liter (IU/L) | Standard Deviation 4.24 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | GGT, Day 28 | 0.8 International unit per liter (IU/L) | Standard Deviation 4.86 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | GGT, Day 42 | 2.5 International unit per liter (IU/L) | Standard Deviation 4.36 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | GGT, Day 42 | -0.5 International unit per liter (IU/L) | Standard Deviation 3.81 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALP, Day 7 | -3.8 International unit per liter (IU/L) | Standard Deviation 3.28 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | AST, Day 7 | -0.4 International unit per liter (IU/L) | Standard Deviation 5.73 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALP, Day 14 | -1.4 International unit per liter (IU/L) | Standard Deviation 5.3 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | GGT, Day 7 | -0.1 International unit per liter (IU/L) | Standard Deviation 2.39 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALP, Day 28 | -1.8 International unit per liter (IU/L) | Standard Deviation 2.82 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | AST, Day 14 | 1.4 International unit per liter (IU/L) | Standard Deviation 5.45 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALP, Day 42 | -1.8 International unit per liter (IU/L) | Standard Deviation 4.73 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | GGT, Day 28 | -2.9 International unit per liter (IU/L) | Standard Deviation 4.41 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALT, Day 7 | -4.1 International unit per liter (IU/L) | Standard Deviation 6.74 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | AST, Day 28 | -3.1 International unit per liter (IU/L) | Standard Deviation 4.95 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALT, Day 14 | -4.4 International unit per liter (IU/L) | Standard Deviation 8.27 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | GGT, Day 14 | -0.1 International unit per liter (IU/L) | Standard Deviation 3.27 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALT, Day 28 | -8.2 International unit per liter (IU/L) | Standard Deviation 10.76 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | AST, Day 42 | -0.3 International unit per liter (IU/L) | Standard Deviation 4.62 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Alkaline Phosphatase (ALP), ALT, Aspartate Aminotransferase (AST) and Gamma Glutamyltransferase (GGT) During Double-blind Treatment Period of Part A | ALT, Day 42 | -7.7 International unit per liter (IU/L) | Standard Deviation 9.31 |
Primary
Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 7 | 5.3 IU/L | Standard Deviation 11.86 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 7 | -1.3 IU/L | Standard Deviation 4.84 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 28 | -2.0 IU/L | Standard Deviation 4.86 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 14 | -2.3 IU/L | Standard Deviation 5.54 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 14 | 5.2 IU/L | Standard Deviation 9.45 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 14 | 0.8 IU/L | Standard Deviation 1.33 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 7 | 0.7 IU/L | Standard Deviation 0.82 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 14 | -1.3 IU/L | Standard Deviation 5.96 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 42 | 4.3 IU/L | Standard Deviation 8.69 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 28 | 0.0 IU/L | Standard Deviation 2.45 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 42 | -3.8 IU/L | Standard Deviation 5.08 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 28 | -0.3 IU/L | Standard Deviation 6.89 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 7 | -1.2 IU/L | Standard Deviation 7.39 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 42 | -0.7 IU/L | Standard Deviation 2.34 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 42 | -4.3 IU/L | Standard Deviation 5.13 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 28 | -2.5 IU/L | Standard Deviation 4.18 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 42 | 2.2 IU/L | Standard Deviation 5.58 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 7 | -1.2 IU/L | Standard Deviation 3.26 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 14 | -1.4 IU/L | Standard Deviation 5.11 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 28 | 0.8 IU/L | Standard Deviation 2.8 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 7 | -0.1 IU/L | Standard Deviation 3.05 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 14 | 0.6 IU/L | Standard Deviation 5.75 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 14 | 1.8 IU/L | Standard Deviation 5.42 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 28 | 0.9 IU/L | Standard Deviation 6.7 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 42 | 1.0 IU/L | Standard Deviation 10.21 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 7 | 5.5 IU/L | Standard Deviation 7.68 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 7 | 1.1 IU/L | Standard Deviation 2.66 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 14 | 1.9 IU/L | Standard Deviation 3.63 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 42 | 0.2 IU/L | Standard Deviation 4.18 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 28 | 2.2 IU/L | Standard Deviation 4.74 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 28 | 2.8 IU/L | Standard Deviation 8.88 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 42 | 3.8 IU/L | Standard Deviation 8.19 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 7 | 1.8 IU/L | Standard Deviation 9.62 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 28 | 6.3 IU/L | Standard Deviation 15.83 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 7 | 0.3 IU/L | Standard Deviation 1.97 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 7 | -0.5 IU/L | Standard Deviation 7.2 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 28 | 2.3 IU/L | Standard Deviation 5.68 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 7 | 1.5 IU/L | Standard Deviation 4.85 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 14 | 5.3 IU/L | Standard Deviation 9.33 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 14 | 3.0 IU/L | Standard Deviation 10.99 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 28 | 0.7 IU/L | Standard Deviation 7.61 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 42 | 0.5 IU/L | Standard Deviation 8.5 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 14 | -1.0 IU/L | Standard Deviation 14.76 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 28 | 0.7 IU/L | Standard Deviation 2.8 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 14 | 6.7 IU/L | Standard Deviation 4.03 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 42 | -0.7 IU/L | Standard Deviation 4.55 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 42 | 1.0 IU/L | Standard Deviation 4.38 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 42 | -0.5 IU/L | Standard Deviation 6.35 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 14 | -0.3 IU/L | Standard Deviation 6.02 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 7 | -2.2 IU/L | Standard Deviation 9.35 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 14 | -3.7 IU/L | Standard Deviation 17.92 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 28 | -2.5 IU/L | Standard Deviation 7.78 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALP, Day 42 | -2.8 IU/L | Standard Deviation 9.53 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 7 | -1.0 IU/L | Standard Deviation 4.61 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 14 | -6.3 IU/L | Standard Deviation 13.85 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 28 | -3.8 IU/L | Standard Deviation 9.63 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | ALT, Day 42 | -4.2 IU/L | Standard Deviation 7.79 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 7 | 0.2 IU/L | Standard Deviation 3.04 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 28 | 1.4 IU/L | Standard Deviation 4.85 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | AST, Day 42 | 1.9 IU/L | Standard Deviation 4.94 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 7 | 1.3 IU/L | Standard Deviation 3.11 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 14 | 2.3 IU/L | Standard Deviation 12.74 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 28 | 0.5 IU/L | Standard Deviation 4.01 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of ALP, ALT, AST and GGT During the Double-blind Treatment Period of Part B and C | GGT, Day 42 | -0.9 IU/L | Standard Deviation 4.52 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study
The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) and Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study | Amylase, Day 42 | 6.0 Units (U)/L | Standard Deviation 10.9 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study | Lipase, Day 42 | 7.5 Units (U)/L | Standard Deviation 21.25 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study | Amylase, Day 42 | 9.2 Units (U)/L | Standard Deviation 29.49 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Amylase and Lipase the Double-blind Treatment Period of Part B of Study | Lipase, Day 42 | 18.8 Units (U)/L | Standard Deviation 71.07 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Direct bilirubin, Day 7 | 0.000 Micromoles (umol)/L | Standard Deviation 1.3962 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Direct bilirubin, Day 14 | 0.428 Micromoles (umol)/L | Standard Deviation 0.855 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Direct bilirubin, Day 28 | -0.428 Micromoles (umol)/L | Standard Deviation 0.855 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Direct bilirubin, Day 42 | -0.855 Micromoles (umol)/L | Standard Deviation 0.9873 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Total bilirubin, Day 7 | 0.000 Micromoles (umol)/L | Standard Deviation 3.694 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Total bilirubin, Day 14 | 0.428 Micromoles (umol)/L | Standard Deviation 1.6372 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Total bilirubin, Day 28 | 1.283 Micromoles (umol)/L | Standard Deviation 3.7917 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Total bilirubin, Day 42 | 0.855 Micromoles (umol)/L | Standard Deviation 2.9618 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Creatinine, Day 7 | 2.2 Micromoles (umol)/L | Standard Deviation 11.12 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Creatinine, Day 14 | -4.4 Micromoles (umol)/L | Standard Deviation 11.41 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Creatinine, Day 28 | 0.0 Micromoles (umol)/L | Standard Deviation 7.22 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Creatinine, Day 42 | -2.2 Micromoles (umol)/L | Standard Deviation 11.12 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Uric acid, Day 7 | -7.4 Micromoles (umol)/L | Standard Deviation 43.27 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Uric acid, Day 14 | -14.9 Micromoles (umol)/L | Standard Deviation 46.71 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Uric acid, Day 28 | -1.5 Micromoles (umol)/L | Standard Deviation 38.05 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Uric acid, Day 42 | -7.4 Micromoles (umol)/L | Standard Deviation 35.15 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Uric acid, Day 42 | -26.2 Micromoles (umol)/L | Standard Deviation 27.5 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Direct bilirubin, Day 7 | -0.311 Micromoles (umol)/L | Standard Deviation 2.2709 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Creatinine, Day 7 | -6.4 Micromoles (umol)/L | Standard Deviation 6.95 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Direct bilirubin, Day 14 | -0.466 Micromoles (umol)/L | Standard Deviation 1.1058 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Uric acid, Day 7 | -10.3 Micromoles (umol)/L | Standard Deviation 39.19 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Direct bilirubin, Day 28 | -0.855 Micromoles (umol)/L | Standard Deviation 1.6618 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Creatinine, Day 14 | -4.8 Micromoles (umol)/L | Standard Deviation 9.97 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Direct bilirubin, Day 42 | -0.171 Micromoles (umol)/L | Standard Deviation 2.2002 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Uric acid, Day 28 | 4.2 Micromoles (umol)/L | Standard Deviation 56.99 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Total bilirubin, Day 7 | -0.777 Micromoles (umol)/L | Standard Deviation 6.4148 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Creatinine, Day 28 | -7.1 Micromoles (umol)/L | Standard Deviation 6.97 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Total bilirubin, Day 14 | -0.933 Micromoles (umol)/L | Standard Deviation 3.0935 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Uric acid, Day 14 | -17.8 Micromoles (umol)/L | Standard Deviation 26.6 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Total bilirubin, Day 28 | -2.565 Micromoles (umol)/L | Standard Deviation 4.13 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Creatinine, Day 42 | -8.8 Micromoles (umol)/L | Standard Deviation 4.17 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part A | Total bilirubin, Day 42 | 0.513 Micromoles (umol)/L | Standard Deviation 5.9264 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 7 | 0.570 umol/L | Standard Deviation 5.9891 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 14 | 0.314 umol/L | Standard Deviation 0.6876 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 28 | 0.513 umol/L | Standard Deviation 0.9366 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 42 | 0.599 umol/L | Standard Deviation 0.8635 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 7 | 0.542 umol/L | Standard Deviation 1.4118 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 14 | -0.570 umol/L | Standard Deviation 4.1418 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 28 | -0.000 umol/L | Standard Deviation 3.2445 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 42 | -1.425 umol/L | Standard Deviation 2.9453 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 7 | 4.6 umol/L | Standard Deviation 6.41 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 14 | -0.1 umol/L | Standard Deviation 3.85 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 28 | 1.9 umol/L | Standard Deviation 6.38 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 42 | -1.0 umol/L | Standard Deviation 3.6 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 7 | 15.9 umol/L | Standard Deviation 54.73 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 14 | -11.9 umol/L | Standard Deviation 37.43 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 28 | 2.0 umol/L | Standard Deviation 61.78 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 42 | -5.0 umol/L | Standard Deviation 29.96 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 14 | -0.611 umol/L | Standard Deviation 2.2851 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 7 | 3.0 umol/L | Standard Deviation 4.1 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 42 | 7.8 umol/L | Standard Deviation 38.35 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 42 | -2.4 umol/L | Standard Deviation 7.48 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 28 | 16.9 umol/L | Standard Deviation 45.09 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 14 | 4.2 umol/L | Standard Deviation 5.61 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 28 | -0.197 umol/L | Standard Deviation 1.1823 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 28 | 2.0 umol/L | Standard Deviation 4.99 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 7 | -0.855 umol/L | Standard Deviation 2.2991 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 28 | 0.132 umol/L | Standard Deviation 3.1578 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 42 | -0.197 umol/L | Standard Deviation 0.5708 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 14 | -0.305 umol/L | Standard Deviation 0.6578 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 7 | 25.1 umol/L | Standard Deviation 30.26 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 42 | 0.263 umol/L | Standard Deviation 2.6898 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 14 | 15.3 umol/L | Standard Deviation 35.74 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 7 | -0.208 umol/L | Standard Deviation 0.6646 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 14 | -0.855 umol/L | Standard Deviation 0.9366 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 7 | -3.705 umol/L | Standard Deviation 4.8867 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 14 | -21.8 umol/L | Standard Deviation 55.88 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 28 | -0.855 umol/L | Standard Deviation 5.1584 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 42 | -0.285 umol/L | Standard Deviation 2.9453 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 42 | 9.9 umol/L | Standard Deviation 11.7 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 7 | 6.9 umol/L | Standard Deviation 5.6 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 14 | 5.7 umol/L | Standard Deviation 8.21 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 28 | -13.9 umol/L | Standard Deviation 54.6 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 28 | 4.9 umol/L | Standard Deviation 7.88 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 42 | 0.6 umol/L | Standard Deviation 3.98 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 7 | -0.513 umol/L | Standard Deviation 1.3594 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 14 | -0.086 umol/L | Standard Deviation 0.1431 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 7 | 3.0 umol/L | Standard Deviation 52.09 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 28 | -0.171 umol/L | Standard Deviation 1.1598 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 42 | -0.200 umol/L | Standard Deviation 0.7978 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 42 | 0.5 umol/L | Standard Deviation 26.78 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 42 | -0.428 umol/L | Standard Deviation 1.6507 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 28 | -0.014 umol/L | Standard Deviation 0.7732 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 7 | -0.200 umol/L | Standard Deviation 0.953 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 14 | 25.3 umol/L | Standard Deviation 50.03 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 28 | 0.998 umol/L | Standard Deviation 2.2424 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 7 | 9.9 umol/L | Standard Deviation 34.81 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 14 | -0.185 umol/L | Standard Deviation 0.9379 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 7 | 0.000 umol/L | Standard Deviation 2.5258 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 14 | 4.6 umol/L | Standard Deviation 6.48 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Total bilirubin, Day 14 | 0.285 umol/L | Standard Deviation 2.5082 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 28 | 8.2 umol/L | Standard Deviation 11.05 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Uric acid, Day 28 | 34.7 umol/L | Standard Deviation 41.27 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 7 | 3.4 umol/L | Standard Deviation 4.47 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Direct bilirubin, Day 42 | -0.328 umol/L | Standard Deviation 0.678 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Direct Bilirubin, Total Bilirubin, Creatinine and Uric Acid During the Double-blind Treatment Period of Part B and C | Creatinine, Day 42 | -0.8 umol/L | Standard Deviation 5.52 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A
The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at on Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Potassium, Day 28 | -0.07 Millimoles (mmol)/L | Standard Deviation 0.419 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Chloride, Day 14 | 1.0 Millimoles (mmol)/L | Standard Deviation 0.82 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Potassium, Day 42 | 0.30 Millimoles (mmol)/L | Standard Deviation 0.673 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Carbon dioxide/Bicarbonate, Day 28 | -0.5 Millimoles (mmol)/L | Standard Deviation 2.08 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Magnesium, Day 7 | -0.0206 Millimoles (mmol)/L | Standard Deviation 0.05306 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Calcium, Day 42 | 0.050 Millimoles (mmol)/L | Standard Deviation 0.0611 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Magnesium, Day 14 | -0.0617 Millimoles (mmol)/L | Standard Deviation 0.07119 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Carbon dioxide/Bicarbonate, Day 42 | -2.5 Millimoles (mmol)/L | Standard Deviation 2.08 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Magnesium, Day 28 | -0.0411 Millimoles (mmol)/L | Standard Deviation 0.05812 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Chloride, Day 28 | -1.5 Millimoles (mmol)/L | Standard Deviation 0.58 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Magnesium, Day 42 | -0.0308 Millimoles (mmol)/L | Standard Deviation 0.02055 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Glucose, Day 7 | -0.0 Millimoles (mmol)/L | Standard Deviation 0.51 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Sodium, Day 7 | 0.3 Millimoles (mmol)/L | Standard Deviation 2.99 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Calcium, Day 28 | 0.056 Millimoles (mmol)/L | Standard Deviation 0.0985 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Sodium, Day 14 | -0.3 Millimoles (mmol)/L | Standard Deviation 1.26 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Glucose, Day 14 | -0.0 Millimoles (mmol)/L | Standard Deviation 0.44 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Sodium, Day 28 | 1.0 Millimoles (mmol)/L | Standard Deviation 3.37 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Chloride, Day 42 | -0.8 Millimoles (mmol)/L | Standard Deviation 1.26 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Sodium, Day 42 | -1.3 Millimoles (mmol)/L | Standard Deviation 2.75 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Glucose, Day 28 | -0.1 Millimoles (mmol)/L | Standard Deviation 0.45 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Urea/BUN, Day 7 | -0.179 Millimoles (mmol)/L | Standard Deviation 1.4428 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Chloride, Day 7 | 0.8 Millimoles (mmol)/L | Standard Deviation 2.5 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Urea/BUN, Day 14 | -0.268 Millimoles (mmol)/L | Standard Deviation 1.1795 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Glucose, Day 42 | -0.2 Millimoles (mmol)/L | Standard Deviation 0.22 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Urea/BUN, Day 28 | -0.536 Millimoles (mmol)/L | Standard Deviation 1.6098 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Carbon dioxide/Bicarbonate, Day 7 | 0.3 Millimoles (mmol)/L | Standard Deviation 1.5 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Urea/BUN, Day 42 | -0.625 Millimoles (mmol)/L | Standard Deviation 2.1095 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Potassium, Day 7 | 0.15 Millimoles (mmol)/L | Standard Deviation 0.387 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Phosphorus inorganic, Day 7 | -0.07 Millimoles (mmol)/L | Standard Deviation 0.165 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Calcium, Day 14 | 0.056 Millimoles (mmol)/L | Standard Deviation 0.0624 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Phosphorus inorganic, Day 14 | -0.14 Millimoles (mmol)/L | Standard Deviation 0.138 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Potassium, Day 14 | 0.20 Millimoles (mmol)/L | Standard Deviation 0.804 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Phosphorus inorganic, Day 28 | -0.02 Millimoles (mmol)/L | Standard Deviation 0.107 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Carbon dioxide/Bicarbonate, Day 14 | -1.0 Millimoles (mmol)/L | Standard Deviation 2.16 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Phosphorus inorganic, Day 42 | 0.01 Millimoles (mmol)/L | Standard Deviation 0.085 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Calcium, Day 7 | -0.025 Millimoles (mmol)/L | Standard Deviation 0.1019 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Phosphorus inorganic, Day 42 | -0.03 Millimoles (mmol)/L | Standard Deviation 0.138 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Calcium, Day 7 | -0.023 Millimoles (mmol)/L | Standard Deviation 0.0718 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Calcium, Day 14 | -0.023 Millimoles (mmol)/L | Standard Deviation 0.0875 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Calcium, Day 28 | -0.010 Millimoles (mmol)/L | Standard Deviation 0.0554 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Calcium, Day 42 | -0.022 Millimoles (mmol)/L | Standard Deviation 0.0729 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Chloride, Day 7 | 1.2 Millimoles (mmol)/L | Standard Deviation 1.89 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Chloride, Day 14 | 0.4 Millimoles (mmol)/L | Standard Deviation 1.63 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Chloride, Day 28 | 0.5 Millimoles (mmol)/L | Standard Deviation 2.12 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Chloride, Day 42 | 0.4 Millimoles (mmol)/L | Standard Deviation 2.12 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Carbon dioxide/Bicarbonate, Day 7 | -1.2 Millimoles (mmol)/L | Standard Deviation 1.72 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Carbon dioxide/Bicarbonate, Day 14 | -1.9 Millimoles (mmol)/L | Standard Deviation 1.64 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Carbon dioxide/Bicarbonate, Day 28 | -1.2 Millimoles (mmol)/L | Standard Deviation 1.75 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Carbon dioxide/Bicarbonate, Day 42 | -2.8 Millimoles (mmol)/L | Standard Deviation 2.44 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Glucose, Day 7 | -0.1 Millimoles (mmol)/L | Standard Deviation 0.35 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Glucose, Day 14 | -0.3 Millimoles (mmol)/L | Standard Deviation 0.37 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Glucose, Day 28 | -0.2 Millimoles (mmol)/L | Standard Deviation 0.33 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Glucose, Day 42 | -0.3 Millimoles (mmol)/L | Standard Deviation 0.28 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Potassium, Day 7 | -0.15 Millimoles (mmol)/L | Standard Deviation 0.491 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Potassium, Day 14 | -0.15 Millimoles (mmol)/L | Standard Deviation 0.406 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Potassium, Day 28 | -0.13 Millimoles (mmol)/L | Standard Deviation 0.419 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Potassium, Day 42 | -0.16 Millimoles (mmol)/L | Standard Deviation 0.548 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Magnesium, Day 7 | -0.0299 Millimoles (mmol)/L | Standard Deviation 0.02658 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Magnesium, Day 14 | -0.0486 Millimoles (mmol)/L | Standard Deviation 0.02478 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Magnesium, Day 28 | -0.0288 Millimoles (mmol)/L | Standard Deviation 0.03384 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Magnesium, Day 42 | -0.0247 Millimoles (mmol)/L | Standard Deviation 0.06484 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Sodium, Day 7 | 0.8 Millimoles (mmol)/L | Standard Deviation 1.6 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Sodium, Day 14 | -0.2 Millimoles (mmol)/L | Standard Deviation 1.78 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Sodium, Day 28 | 1.9 Millimoles (mmol)/L | Standard Deviation 2.23 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Sodium, Day 42 | -0.6 Millimoles (mmol)/L | Standard Deviation 1.65 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Urea/BUN, Day 7 | -0.325 Millimoles (mmol)/L | Standard Deviation 0.7732 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Urea/BUN, Day 14 | -0.746 Millimoles (mmol)/L | Standard Deviation 0.6859 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Urea/BUN, Day 28 | -0.643 Millimoles (mmol)/L | Standard Deviation 1.1264 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Urea/BUN, Day 42 | -0.678 Millimoles (mmol)/L | Standard Deviation 0.7794 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Phosphorus inorganic, Day 7 | -0.04 Millimoles (mmol)/L | Standard Deviation 0.09 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Phosphorus inorganic, Day 14 | -0.05 Millimoles (mmol)/L | Standard Deviation 0.071 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic and Urea/Blood Urea Nitrogen (BUN) During the Double-blind Treatment Period of Part A | Phosphorus inorganic, Day 28 | -0.09 Millimoles (mmol)/L | Standard Deviation 0.112 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C
The electrolytes include calcium, chloride, carbon dioxide content/bicarbonate, potassium, magnesium and sodium. Assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 7 | 0.083 mmol/L | Standard Deviation 0.0604 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 14 | 0.050 mmol/L | Standard Deviation 0.0985 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 28 | 0.021 mmol/L | Standard Deviation 0.0677 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 42 | -0.025 mmol/L | Standard Deviation 0.0523 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 7 | -1.5 mmol/L | Standard Deviation 1.38 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 14 | -0.8 mmol/L | Standard Deviation 2.64 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 28 | 0.8 mmol/L | Standard Deviation 2.79 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 42 | -1.0 mmol/L | Standard Deviation 2.1 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 7 | 0.0 mmol/L | Standard Deviation 2.1 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 14 | -1.8 mmol/L | Standard Deviation 1.94 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 28 | -1.0 mmol/L | Standard Deviation 2.28 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 42 | 0.5 mmol/L | Standard Deviation 2.59 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 7 | -0.3 mmol/L | Standard Deviation 1.32 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 14 | -0.1 mmol/L | Standard Deviation 1.17 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 28 | -0.1 mmol/L | Standard Deviation 1.71 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 42 | 0.2 mmol/L | Standard Deviation 1.06 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 7 | 0.33 mmol/L | Standard Deviation 0.301 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 14 | 0.17 mmol/L | Standard Deviation 0.258 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 28 | 0.28 mmol/L | Standard Deviation 0.172 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 42 | -0.05 mmol/L | Standard Deviation 0.266 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 7 | 0.0206 mmol/L | Standard Deviation 0.05665 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 14 | -0.0206 mmol/L | Standard Deviation 0.07236 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 28 | 0.0274 mmol/L | Standard Deviation 0.08879 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 42 | -0.0137 mmol/L | Standard Deviation 0.07197 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 7 | 1.2 mmol/L | Standard Deviation 2.04 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 14 | 1.3 mmol/L | Standard Deviation 1.97 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 28 | 1.8 mmol/L | Standard Deviation 1.94 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 42 | 0.5 mmol/L | Standard Deviation 0.84 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 7 | -0.000 mmol/L | Standard Deviation 0.714 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 14 | -0.297 mmol/L | Standard Deviation 0.9423 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 28 | 0.119 mmol/L | Standard Deviation 1.8435 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 42 | -0.595 mmol/L | Standard Deviation 0.4323 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Cholesterol, Day 42 | -0.853 mmol/L | — |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 7 | 0.10 mmol/L | Standard Deviation 0.144 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 14 | 0.01 mmol/L | Standard Deviation 0.069 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 28 | 0.06 mmol/L | Standard Deviation 0.107 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 42 | 0.01 mmol/L | Standard Deviation 0.053 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 28 | -0.01 mmol/L | Standard Deviation 0.162 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 7 | 0.053 mmol/L | Standard Deviation 0.0763 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 14 | 0.128 mmol/L | Standard Deviation 0.9456 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 42 | 0.01 mmol/L | Standard Deviation 0.266 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 7 | -2.0 mmol/L | Standard Deviation 3.53 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 42 | -0.4 mmol/L | Standard Deviation 2.9 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 28 | 1.7 mmol/L | Standard Deviation 2.87 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 7 | 0.0294 mmol/L | Standard Deviation 0.04394 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 14 | 0.2 mmol/L | Standard Deviation 2.1 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 14 | 0.05 mmol/L | Standard Deviation 0.09 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 14 | 1.4 mmol/L | Standard Deviation 2.98 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 14 | 0.0176 mmol/L | Standard Deviation 0.06184 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 28 | 0.302 mmol/L | Standard Deviation 0.7552 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 42 | -0.04 mmol/L | Standard Deviation 0.153 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 7 | 0.01 mmol/L | Standard Deviation 0.089 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 28 | 0.0379 mmol/L | Standard Deviation 0.08951 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 14 | -0.1 mmol/L | Standard Deviation 1.96 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 7 | 0.2 mmol/L | Standard Deviation 2.58 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 42 | -0.412 mmol/L | Standard Deviation 0.8603 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 42 | 0.0063 mmol/L | Standard Deviation 0.06014 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 28 | -0.2 mmol/L | Standard Deviation 2.31 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 42 | -1.8 mmol/L | Standard Deviation 1.91 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 7 | -1.2 mmol/L | Standard Deviation 1.48 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 28 | -0.4 mmol/L | Standard Deviation 2.47 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 42 | -0.1 mmol/L | Standard Deviation 2.3 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 42 | 0.2 mmol/L | Standard Deviation 1.96 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 42 | -0.040 mmol/L | Standard Deviation 0.1168 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 14 | -1.9 mmol/L | Standard Deviation 3.32 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 7 | 0.09 mmol/L | Standard Deviation 0.369 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 28 | 0.2 mmol/L | Standard Deviation 1.17 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 28 | 0.046 mmol/L | Standard Deviation 0.1063 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 7 | 0.383 mmol/L | Standard Deviation 1.0522 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 14 | 0.20 mmol/L | Standard Deviation 0.353 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 7 | 0.3 mmol/L | Standard Deviation 3.29 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 14 | 0.041 mmol/L | Standard Deviation 0.1079 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Cholesterol, Day 42 | -0.103 mmol/L | Standard Deviation 0.4579 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 28 | 0.08 mmol/L | Standard Deviation 0.365 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 28 | 0.004 mmol/L | Standard Deviation 0.0695 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 14 | -2.0 mmol/L | Standard Deviation 3.1 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 28 | -2.3 mmol/L | Standard Deviation 2.34 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 28 | 0.714 mmol/L | Standard Deviation 2.0195 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 42 | -2.8 mmol/L | Standard Deviation 2.14 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 7 | 0.9 mmol/L | Standard Deviation 2.41 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 28 | -0.12 mmol/L | Standard Deviation 0.187 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 14 | 0.5 mmol/L | Standard Deviation 2.06 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 28 | 1.5 mmol/L | Standard Deviation 2.71 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 42 | -0.655 mmol/L | Standard Deviation 0.4745 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 42 | 1.2 mmol/L | Standard Deviation 0.7 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 7 | 0.28 mmol/L | Standard Deviation 0.264 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 14 | 0.17 mmol/L | Standard Deviation 0.427 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 28 | 0.10 mmol/L | Standard Deviation 0.253 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Cholesterol, Day 42 | -0.052 mmol/L | Standard Deviation 0.256 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 42 | -0.05 mmol/L | Standard Deviation 0.302 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 7 | 0.0206 mmol/L | Standard Deviation 0.05034 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 14 | 0.0069 mmol/L | Standard Deviation 0.05463 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 28 | 0.0411 mmol/L | Standard Deviation 0.09005 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 7 | -0.03 mmol/L | Standard Deviation 0.186 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 42 | -0.0274 mmol/L | Standard Deviation 0.03356 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 7 | 1.3 mmol/L | Standard Deviation 1.51 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 14 | 1.5 mmol/L | Standard Deviation 1.05 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 28 | 1.0 mmol/L | Standard Deviation 1.26 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 14 | -0.10 mmol/L | Standard Deviation 0.193 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 42 | -1.0 mmol/L | Standard Deviation 1.79 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 7 | 0.025 mmol/L | Standard Deviation 0.0879 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 14 | 0.067 mmol/L | Standard Deviation 0.07 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 7 | 0.179 mmol/L | Standard Deviation 0.6679 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 42 | -0.071 mmol/L | Standard Deviation 0.0533 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 7 | 0.8 mmol/L | Standard Deviation 2.93 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 42 | -0.05 mmol/L | Standard Deviation 0.097 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 14 | 0.5 mmol/L | Standard Deviation 2.07 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 28 | 1.0 mmol/L | Standard Deviation 2.45 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 14 | 0.178 mmol/L | Standard Deviation 1.9258 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 42 | 0.5 mmol/L | Standard Deviation 2.35 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 7 | -2.0 mmol/L | Standard Deviation 2 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 42 | -1.0 mmol/L | Standard Deviation 2.09 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 28 | -0.07 mmol/L | Standard Deviation 0.352 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 28 | -0.3 mmol/L | Standard Deviation 2.83 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 7 | -0.004 mmol/L | Standard Deviation 0.0991 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 14 | 0.03 mmol/L | Standard Deviation 0.143 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 14 | 0.07 mmol/L | Standard Deviation 0.355 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 28 | 0.3 mmol/L | Standard Deviation 1.5 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 14 | 0.017 mmol/L | Standard Deviation 0.1215 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 28 | 0.12 mmol/L | Standard Deviation 0.116 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 7 | 0.06 mmol/L | Standard Deviation 0.368 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 42 | -0.387 mmol/L | Standard Deviation 1.0035 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 28 | 0.035 mmol/L | Standard Deviation 0.1352 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 14 | -0.7 mmol/L | Standard Deviation 2.42 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 42 | 0.1 mmol/L | Standard Deviation 1.62 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 42 | -1.3 mmol/L | Standard Deviation 3.14 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Calcium, Day 42 | -0.056 mmol/L | Standard Deviation 0.0775 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 7 | -0.208 mmol/L | Standard Deviation 1.0597 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 28 | -2.0 mmol/L | Standard Deviation 2.76 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Carbon dioxide/Bicarbonate, Day 7 | -0.6 mmol/L | Standard Deviation 2.11 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 7 | 0.4 mmol/L | Standard Deviation 1.51 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 42 | 0.3 mmol/L | Standard Deviation 0.98 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 42 | -0.0171 mmol/L | Standard Deviation 0.09349 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 7 | 0.01 mmol/L | Standard Deviation 0.116 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 28 | 0.0240 mmol/L | Standard Deviation 0.11284 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 14 | -2.2 mmol/L | Standard Deviation 2.44 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 7 | 0.8 mmol/L | Standard Deviation 1.7 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 14 | 0.0206 mmol/L | Standard Deviation 0.11153 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Phosphorus inorganic, Day 42 | -0.00 mmol/L | Standard Deviation 0.094 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 14 | -0.268 mmol/L | Standard Deviation 1.1804 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 14 | 1.5 mmol/L | Standard Deviation 2.07 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Magnesium, Day 7 | -0.0206 mmol/L | Standard Deviation 0.08496 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Cholesterol, Day 42 | -0.155 mmol/L | Standard Deviation 0.4389 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Chloride, Day 14 | 0.6 mmol/L | Standard Deviation 1.88 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Sodium, Day 28 | 0.6 mmol/L | Standard Deviation 1.16 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Glucose, Day 7 | -1.7 mmol/L | Standard Deviation 1.86 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Potassium, Day 42 | 0.08 mmol/L | Standard Deviation 0.564 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Electrolytes, Glucose Phosphorus Inorganic, BUN and Cholesterol During the Double-blind Treatment Period of Part B and C | Urea/BUN, Day 28 | 0.863 mmol/L | Standard Deviation 1.3223 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Day 7 | -1.256 Picomoles (pmol)/L | Standard Deviation 26.7142 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Day 28 | -11.659 Picomoles (pmol)/L | Standard Deviation 16.5012 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Day 14 | 8.072 Picomoles (pmol)/L | Standard Deviation 32.6673 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Day 42 | -22.721 Picomoles (pmol)/L | Standard Deviation 17.5213 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Day 42 | -13.735 Picomoles (pmol)/L | Standard Deviation 11.7418 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Day 7 | 12.516 Picomoles (pmol)/L | Standard Deviation 28.0792 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Day 14 | 1.973 Picomoles (pmol)/L | Standard Deviation 13.8798 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part A | Day 28 | 8.969 Picomoles (pmol)/L | Standard Deviation 42.2377 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 7 | -20.21 pmol/L | Standard Deviation 33.619 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 14 | -21.65 pmol/L | Standard Deviation 61.873 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 28 | -53.41 pmol/L | Standard Deviation 48.574 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 42 | -12.99 pmol/L | Standard Deviation 40.953 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 14 | -9.62 pmol/L | Standard Deviation 62.083 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 28 | -35.18 pmol/L | Standard Deviation 76.905 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 42 | -8.12 pmol/L | Standard Deviation 48.862 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 7 | -20.05 pmol/L | Standard Deviation 90.341 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 28 | 34.28 pmol/L | Standard Deviation 70.064 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 14 | -79.39 pmol/L | Standard Deviation 33.851 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 42 | 34.28 pmol/L | Standard Deviation 36.025 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 7 | 45.11 pmol/L | Standard Deviation 44.635 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 42 | 35.28 pmol/L | Standard Deviation 61.179 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 14 | -41.14 pmol/L | Standard Deviation 67.791 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 7 | -29.59 pmol/L | Standard Deviation 41.312 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Insulin During the Double-blind Treatment Period of Part B and C | Day 28 | -7.22 pmol/L | Standard Deviation 39.675 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C | Day 42 | 0.137 Milliunits (mu/L) | Standard Deviation 0.5036 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C | Day 7 | -5.790 Milliunits (mu/L) | — |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C | Day 42 | -0.067 Milliunits (mu/L) | Standard Deviation 0.2826 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C | Day 42 | -0.187 Milliunits (mu/L) | Standard Deviation 0.8308 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Thyroid Stimulating Hormone During the Double-blind Treatment Period of Part B and C | Day 42 | 0.149 Milliunits (mu/L) | Standard Deviation 0.3342 |
Primary
Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1 and Day 42. Baseline value was defined as the assessment done Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42) value. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) and Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Total thyroxine | 0.8578 Nanomoles (nmol)/L | Standard Deviation 7.70771 |
| Part A-Placebo | Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Total T3 | -0.3 Nanomoles (nmol)/L | — |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Total T3 | 0.1 Nanomoles (nmol)/L | Standard Deviation 0.31 |
| Part A-GSK2890457 | Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Total thyroxine | 1.0891 Nanomoles (nmol)/L | Standard Deviation 6.62201 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Total thyroxine | -5.1478 Nanomoles (nmol)/L | Standard Deviation 7.09618 |
| Part C-Placebo+Metformin | Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Total T3 | -0.2 Nanomoles (nmol)/L | Standard Deviation 0.15 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Total thyroxine | -2.3597 Nanomoles (nmol)/L | Standard Deviation 8.19189 |
| Part C-GSK2890457+Metformin | Change From Baseline in Clinical Chemistry Parameters of Total Thyroxine and Total T3 During the Double-blind Treatment Period of Part B and C | Total T3 | -0.2 Nanomoles (nmol)/L | Standard Deviation 0.16 |
Primary
Change From Baseline in ECG Intervals During Part B and C
Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QTcB, QTcF and RR intervals. The assessments were done at Day -1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Follow-up (Day 56)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | QT Interval, Day 42 | 8.11 Milliseconds | Standard Deviation 10.477 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | QRS Duration, Follow-up | 0.11 Milliseconds | Standard Deviation 2.903 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | PR Interval, Follow-up | -1.11 Milliseconds | Standard Deviation 14.327 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | QTcF, Day 42 | 1.17 Milliseconds | Standard Deviation 9.777 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | QRS Duration, Day 42 | 0.78 Milliseconds | Standard Deviation 3.897 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | QTcB, Follow-up | -5.89 Milliseconds | Standard Deviation 7.088 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | RR Interval, Follow-up | 0.03 Milliseconds | Standard Deviation 0.107 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | RR Interval, Day 42 | 0.04 Milliseconds | Standard Deviation 0.045 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | QTcB, Day 42 | -2.87 Milliseconds | Standard Deviation 12.081 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | QT Interval, Follow-up | 1.44 Milliseconds | Standard Deviation 27.022 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | PR Interval, Day 42 | 5.56 Milliseconds | Standard Deviation 6.206 |
| Part A-Placebo | Change From Baseline in ECG Intervals During Part B and C | QTcF, Follow-up | -3.17 Milliseconds | Standard Deviation 11.117 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | QTcB, Day 42 | -1.51 Milliseconds | Standard Deviation 14.358 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | RR Interval, Day 42 | -0.00 Milliseconds | Standard Deviation 0.086 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | RR Interval, Follow-up | 0.02 Milliseconds | Standard Deviation 0.127 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | PR Interval, Day 42 | 3.08 Milliseconds | Standard Deviation 14.104 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | PR Interval, Follow-up | -3.69 Milliseconds | Standard Deviation 11.708 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | QRS Duration, Day 42 | -2.62 Milliseconds | Standard Deviation 3.049 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | QRS Duration, Follow-up | -1.69 Milliseconds | Standard Deviation 5.985 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | QT Interval, Day 42 | -1.69 Milliseconds | Standard Deviation 17.212 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | QT Interval, Follow-up | -5.69 Milliseconds | Standard Deviation 25.885 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | QTcB, Follow-up | -10.95 Milliseconds | Standard Deviation 14.939 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | QTcF, Day 42 | -1.49 Milliseconds | Standard Deviation 11.971 |
| Part A-GSK2890457 | Change From Baseline in ECG Intervals During Part B and C | QTcF, Follow-up | -9.10 Milliseconds | Standard Deviation 12.639 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | RR Interval, Day 42 | 0.01 Milliseconds | Standard Deviation 0.12 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | PR Interval, Day 42 | -6.44 Milliseconds | Standard Deviation 8.334 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | QT Interval, Day 42 | 2.78 Milliseconds | Standard Deviation 17.711 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | QTcF, Day 42 | 1.22 Milliseconds | Standard Deviation 7.799 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | QT Interval, Follow-up | 0.78 Milliseconds | Standard Deviation 7.559 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | RR Interval, Follow-up | 0.02 Milliseconds | Standard Deviation 0.091 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | QTcF, Follow-up | -1.78 Milliseconds | Standard Deviation 9.34 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | QTcB, Day 42 | 0.43 Milliseconds | Standard Deviation 13.099 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | QTcB, Follow-up | -3.20 Milliseconds | Standard Deviation 15.699 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | PR Interval, Follow-up | -3.11 Milliseconds | Standard Deviation 5.652 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | QRS Duration, Day 42 | 0.11 Milliseconds | Standard Deviation 4.204 |
| Part C-Placebo+Metformin | Change From Baseline in ECG Intervals During Part B and C | QRS Duration, Follow-up | 0.78 Milliseconds | Standard Deviation 1.76 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | QTcB, Follow-up | -2.14 Milliseconds | Standard Deviation 17.641 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | QRS Duration, Follow-up | 0.11 Milliseconds | Standard Deviation 3.421 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | QTcB, Day 42 | -4.23 Milliseconds | Standard Deviation 11.896 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | QTcF, Follow-up | -3.50 Milliseconds | Standard Deviation 13.849 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | RR Interval, Day 42 | 0.02 Milliseconds | Standard Deviation 0.074 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | QT Interval, Day 42 | 0.78 Milliseconds | Standard Deviation 15.431 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | RR Interval, Follow-up | -0.01 Milliseconds | Standard Deviation 0.088 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | QTcF, Day 42 | -2.58 Milliseconds | Standard Deviation 10.229 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | PR Interval, Day 42 | -4.44 Milliseconds | Standard Deviation 10.156 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | QT Interval, Follow-up | -5.56 Milliseconds | Standard Deviation 17.22 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | PR Interval, Follow-up | -6.28 Milliseconds | Standard Deviation 13.676 |
| Part C-GSK2890457+Metformin | Change From Baseline in ECG Intervals During Part B and C | QRS Duration, Day 42 | -1.06 Milliseconds | Standard Deviation 2.947 |
Primary
Change From Baseline in Electrocardiogram (ECG) Intervals During Part A
Single 12-lead ECGs was obtained after participants rested in a supine position for at least 10 minutes using an ECG machine that automatically calculated the HR and measured PR, QRS, QT, QT duration corrected for HR by Fridericia's formula (QTcF) and QT duration corrected for HR by Bazett's formula (QTcB intervals. The assessments were done at Day 1 (pre-dose, triplicate), Day 42 (pre-dose) and Follow-up Visit. Baseline value was defined as the average of the triplicate pre-dose assessments done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 42 and Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Follow-up (Day 56)
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | PR Interval, Day 42 | 6.3 Milliseconds | Standard Deviation 11 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | PR Interval, Follow-up | 9.0 Milliseconds | Standard Deviation 10.26 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QRS Duration, Day 42 | 2.2 Milliseconds | Standard Deviation 3.91 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QRS Duration, Follow-up | 3.9 Milliseconds | Standard Deviation 6.05 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QT Interval, Day 42 | 10.8 Milliseconds | Standard Deviation 13.52 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QT Interval, Follow-up | 0.3 Milliseconds | Standard Deviation 19.29 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QTcB, Day 42 | 8.2 Milliseconds | Standard Deviation 14.56 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QTcB, Follow-up | 6.9 Milliseconds | Standard Deviation 9.5 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QTcF, Day 42 | 9.1 Milliseconds | Standard Deviation 12.61 |
| Part A-Placebo | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QTcF, Follow-up | 4.8 Milliseconds | Standard Deviation 7.81 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QTcB, Follow-up | 6.3 Milliseconds | Standard Deviation 15.65 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | PR Interval, Day 42 | 1.1 Milliseconds | Standard Deviation 8.2 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QT Interval, Follow-up | -10.2 Milliseconds | Standard Deviation 12.81 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | PR Interval, Follow-up | 1.5 Milliseconds | Standard Deviation 8.3 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QTcF, Follow-up | 0.7 Milliseconds | Standard Deviation 11.34 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QRS Duration, Day 42 | -2.1 Milliseconds | Standard Deviation 3.1 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QTcB, Day 42 | -3.3 Milliseconds | Standard Deviation 14.89 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QRS Duration, Follow-up | -0.7 Milliseconds | Standard Deviation 6.4 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QTcF, Day 42 | 3.2 Milliseconds | Standard Deviation 11.85 |
| Part A-GSK2890457 | Change From Baseline in Electrocardiogram (ECG) Intervals During Part A | QT Interval, Day 42 | 16.4 Milliseconds | Standard Deviation 20.32 |
Primary
Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C
Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean.
Time frame: Baseline (Day -1) and Day 42 of Part B and C
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Placebo | Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C | -0.384 mmol/L | Standard Error 0.556 |
| Part A-GSK2890457 | Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C | -0.230 mmol/L | Standard Error 0.375 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C | 0.136 mmol/L | Standard Error 0.52 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Glucose During the Double-blind Treatment Period of Part B and C | -0.387 mmol/L | Standard Error 0.351 |
Comparison: Part B-Placebo+Liraglutide versus Part B-GSK2890457+Liraglutide for Day 42 change from Baseline in fasting glucose.95% CI: [-1.277, 1.587]ANCOVA
Comparison: Part C-Placebo+Metformin versus Part C-GSK2890457+Metformin for Day 42 change from Baseline in fasting glucose.95% CI: [-1.939, 0.892]ANCOVA
Primary
Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C
Two fasting samples 5 minutes apart were taken for insulin. Baseline insulin level was the average of the 2 fasting samples. For insulin weighted mean AUC (0-4 hour) and weighted mean AUC (0-24 hour) was calculated for Baseline (Day -1) and end of treatment (Day 42). AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean insulin AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast.
Time frame: Baseline (Day -1) and Day 42
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Fasting Insulin | -4.887 pmol/L | Standard Deviation 16.5321 |
| Part A-Placebo | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Insulin Weighted Mean AUC 0-24 hour | 1.626 pmol/L | Standard Deviation 50.3186 |
| Part A-Placebo | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Insulin Weighted Mean AUC 0-4 hour | 69.635 pmol/L | Standard Deviation 31.8542 |
| Part A-GSK2890457 | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Fasting Insulin | 1.133 pmol/L | Standard Deviation 20.2106 |
| Part A-GSK2890457 | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Insulin Weighted Mean AUC 0-24 hour | -13.905 pmol/L | Standard Deviation 42.6248 |
| Part A-GSK2890457 | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Insulin Weighted Mean AUC 0-4 hour | 14.589 pmol/L | Standard Deviation 67.3782 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Insulin Weighted Mean AUC 0-4 hour | 57.887 pmol/L | Standard Deviation 74.4685 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Fasting Insulin | -11.946 pmol/L | Standard Deviation 28.0383 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Insulin Weighted Mean AUC 0-24 hour | 22.740 pmol/L | Standard Deviation 50.2234 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Fasting Insulin | 12.300 pmol/L | Standard Deviation 45.8067 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Insulin Weighted Mean AUC 0-24 hour | 17.134 pmol/L | Standard Deviation 79.9432 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Insulin and Weighted Mean Insulin AUC (0-4 Hour) and AUC (0-24 Hour) During the Double-blind Treatment Period of Part B and C | Insulin Weighted Mean AUC 0-4 hour | 10.322 pmol/L | Standard Deviation 81.6157 |
Primary
Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C
The assessments were done at Day -1, Day 7, Day 14, Day 28, Day 42 and Follow-up Visit. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline (Day 7, 14, 28, 42 and Follow-up visit) values.
Time frame: Baseline (Day -1) up to Follow-up (Day 56)
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 42 | 0.194 mmol/L | Standard Deviation 1.063 |
| Part A-Placebo | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 14 | -0.093 mmol/L | Standard Deviation 1.1748 |
| Part A-Placebo | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Follow-up | 0.962 mmol/L | Standard Deviation 1.9719 |
| Part A-Placebo | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 28 | -0.111 mmol/L | Standard Deviation 1.7135 |
| Part A-Placebo | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 7 | -0.278 mmol/L | Standard Deviation 1.3178 |
| Part A-GSK2890457 | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 28 | -0.201 mmol/L | Standard Deviation 2.3145 |
| Part A-GSK2890457 | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 42 | -0.098 mmol/L | Standard Deviation 2.2967 |
| Part A-GSK2890457 | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Follow-up | 0.444 mmol/L | Standard Deviation 3.0739 |
| Part A-GSK2890457 | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 14 | 0.210 mmol/L | Standard Deviation 2.0999 |
| Part A-GSK2890457 | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 7 | 0.285 mmol/L | Standard Deviation 3.2948 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 28 | 1.536 mmol/L | Standard Deviation 2.7121 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 7 | 0.879 mmol/L | Standard Deviation 2.409 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 14 | 0.518 mmol/L | Standard Deviation 2.0551 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 42 | 1.184 mmol/L | Standard Deviation 0.6983 |
| Part C-Placebo+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Follow-up | 1.249 mmol/L | Standard Deviation 1.9061 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 42 | 0.074 mmol/L | Standard Deviation 1.6151 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 14 | -2.216 mmol/L | Standard Deviation 2.4434 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 7 | -1.665 mmol/L | Standard Deviation 1.8607 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Day 28 | -1.989 mmol/L | Standard Deviation 2.7612 |
| Part C-GSK2890457+Metformin | Change From Baseline in Fasting Plasma Glucose (Safety Laboratory) Values During the Double-blind Treatment Period of Part B and C | Follow-up | -1.226 mmol/L | Standard Deviation 1.3623 |
Primary
Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C
Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Adjusted mean is reported as LS mean.
Time frame: Baseline (Day -1) and Day 42
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A-Placebo | Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C | -0.214 Percent of TL hemoglobin | Standard Error 0.167 |
| Part A-GSK2890457 | Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C | -0.278 Percent of TL hemoglobin | Standard Error 0.113 |
| Part C-Placebo+Metformin | Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C | 0.018 Percent of TL hemoglobin | Standard Error 0.264 |
| Part C-GSK2890457+Metformin | Change From Baseline in Glycated Hemoglobin (HbA1c) During the Double-blind Treatment Period of Part B and C | -0.201 Percent of TL hemoglobin | Standard Error 0.187 |
Comparison: Part B-Placebo+Liraglutide versus Part B-GSK2890457+Liraglutide for Day 42 change from Baseline in HbA1c.95% CI: [-0.495, 0.365]ANCOVA
Comparison: Part C-Placebo+Metformin versus Part C-GSK2890457+Metformin for Day 42 change from Baseline in HbA1c.95% CI: [-0.91, 0.472]ANCOVA
Primary
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Day 7 | 0.0000 Ratio | Standard Deviation 0.00365 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Day 14 | 0.0128 Ratio | Standard Deviation 0.00943 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Day 28 | 0.0228 Ratio | Standard Deviation 0.01921 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Day 42 | 0.0060 Ratio | Standard Deviation 0.0278 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Day 42 | -0.0089 Ratio | Standard Deviation 0.02614 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Day 7 | -0.0128 Ratio | Standard Deviation 0.01836 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Day 28 | -0.0066 Ratio | Standard Deviation 0.01127 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part A | Day 14 | -0.0026 Ratio | Standard Deviation 0.01975 |
Primary
Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 7 | 0.0032 Ratio | Standard Deviation 0.0124 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 14 | -0.0028 Ratio | Standard Deviation 0.02218 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 28 | -0.0003 Ratio | Standard Deviation 0.009 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 42 | -0.0022 Ratio | Standard Deviation 0.01032 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 14 | 0.0011 Ratio | Standard Deviation 0.0203 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 28 | -0.0003 Ratio | Standard Deviation 0.02237 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 42 | -0.0025 Ratio | Standard Deviation 0.01509 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 7 | 0.0019 Ratio | Standard Deviation 0.01645 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 28 | -0.0010 Ratio | Standard Deviation 0.02832 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 14 | 0.0057 Ratio | Standard Deviation 0.01628 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 42 | -0.0087 Ratio | Standard Deviation 0.01154 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 7 | -0.0082 Ratio | Standard Deviation 0.01837 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 42 | -0.0159 Ratio | Standard Deviation 0.01827 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 14 | -0.0036 Ratio | Standard Deviation 0.03707 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 7 | -0.0072 Ratio | Standard Deviation 0.02007 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of Hematocrit During the Double-blind Treatment Period of Part B and C | Day 28 | 0.0003 Ratio | Standard Deviation 0.02786 |
Primary
Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 7 | -0.02 Picograms | Standard Deviation 0.16 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 14 | 0.18 Picograms | Standard Deviation 0.319 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 28 | 0.17 Picograms | Standard Deviation 0.484 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 42 | -0.12 Picograms | Standard Deviation 0.412 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 14 | -0.10 Picograms | Standard Deviation 0.476 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 28 | 0.01 Picograms | Standard Deviation 0.487 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 42 | 0.08 Picograms | Standard Deviation 0.668 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 7 | -0.21 Picograms | Standard Deviation 0.315 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 28 | -0.20 Picograms | Standard Deviation 0.41 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 14 | -0.25 Picograms | Standard Deviation 0.689 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 42 | -0.28 Picograms | Standard Deviation 0.5 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 7 | -0.23 Picograms | Standard Deviation 0.314 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 42 | 0.02 Picograms | Standard Deviation 0.333 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 14 | 0.03 Picograms | Standard Deviation 0.454 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 7 | -0.18 Picograms | Standard Deviation 0.434 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of MCH During the Double-blind Treatment Period of Part B and C | Day 28 | -0.08 Picograms | Standard Deviation 0.343 |
Primary
Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 7 | 0.35 Femtoliters | Standard Deviation 1.067 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 14 | 0.02 Femtoliters | Standard Deviation 0.659 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 28 | 0.05 Femtoliters | Standard Deviation 0.967 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 42 | -0.90 Femtoliters | Standard Deviation 1.279 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 14 | 0.54 Femtoliters | Standard Deviation 1.134 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 28 | 0.55 Femtoliters | Standard Deviation 1.381 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 42 | 0.07 Femtoliters | Standard Deviation 1.768 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 7 | 0.39 Femtoliters | Standard Deviation 1.296 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 28 | -0.18 Femtoliters | Standard Deviation 1.465 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 14 | -0.47 Femtoliters | Standard Deviation 1.544 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 42 | -0.78 Femtoliters | Standard Deviation 1.468 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 7 | 0.40 Femtoliters | Standard Deviation 0.443 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 42 | -0.27 Femtoliters | Standard Deviation 1.263 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 14 | 0.76 Femtoliters | Standard Deviation 1.925 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 7 | 0.25 Femtoliters | Standard Deviation 1.119 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameter of MCV During the Double-blind Treatment Period of Part B and C | Day 28 | 0.17 Femtoliters | Standard Deviation 1.303 |
Primary
Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Day 7 | 0.25 Picograms | Standard Deviation 0.42 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Day 14 | 0.27 Picograms | Standard Deviation 0.881 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Day 28 | 0.70 Picograms | Standard Deviation 0.816 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Day 42 | 1.40 Picograms | Standard Deviation 0.841 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Day 42 | 0.89 Picograms | Standard Deviation 0.924 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Day 7 | 0.31 Picograms | Standard Deviation 0.589 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Day 28 | 0.37 Picograms | Standard Deviation 0.427 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) During the Double-blind Treatment Period of Part A | Day 14 | 0.32 Picograms | Standard Deviation 0.453 |
Primary
Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Day 7 | 0.15 Femtoliters | Standard Deviation 1.323 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Day 14 | 0.85 Femtoliters | Standard Deviation 1.348 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Day 28 | -0.30 Femtoliters | Standard Deviation 1.393 |
| Part A-Placebo | Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Day 42 | -0.90 Femtoliters | Standard Deviation 1.219 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Day 42 | 0.35 Femtoliters | Standard Deviation 1.866 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Day 7 | -0.55 Femtoliters | Standard Deviation 0.792 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Day 28 | -0.62 Femtoliters | Standard Deviation 1.105 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameter of Mean Corpuscle Volume (MCV) During the Double-blind Treatment Period of Part A | Day 14 | 0.95 Femtoliters | Standard Deviation 0.682 |
Primary
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 7 | 0.0270 GI/L | Standard Deviation 0.03653 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 28 | 0.08 GI/L | Standard Deviation 0.728 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 42 | 0.00 GI/L | Standard Deviation 0.1 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 7 | 0.02 GI/L | Standard Deviation 0.04 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 7 | 18.3 GI/L | Standard Deviation 24.21 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 7 | 0.27 GI/L | Standard Deviation 0.431 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 14 | 0.38 GI/L | Standard Deviation 0.932 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 28 | 0.03 GI/L | Standard Deviation 0.147 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 42 | -0.24 GI/L | Standard Deviation 0.404 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 28 | -0.01 GI/L | Standard Deviation 0.608 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 14 | 0.01 GI/L | Standard Deviation 0.032 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 14 | 0.52 GI/L | Standard Deviation 0.997 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 28 | 0.01 GI/L | Standard Deviation 0.049 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 42 | -0.20 GI/L | Standard Deviation 0.533 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 42 | 0.01 GI/L | Standard Deviation 0.045 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 28 | -0.0002 GI/L | Standard Deviation 0.01418 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 7 | 0.65 GI/L | Standard Deviation 0.582 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 7 | 0.31 GI/L | Standard Deviation 0.333 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 14 | 0.18 GI/L | Standard Deviation 0.275 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 42 | -2.0 GI/L | Standard Deviation 23.13 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 28 | 0.08 GI/L | Standard Deviation 0.3 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 42 | 0.02 GI/L | Standard Deviation 0.158 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 42 | 0.0098 GI/L | Standard Deviation 0.00895 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 28 | 4.5 GI/L | Standard Deviation 23.87 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 7 | 0.04 GI/L | Standard Deviation 0.109 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 14 | -0.05 GI/L | Standard Deviation 0.125 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 14 | 0.0037 GI/L | Standard Deviation 0.01122 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 14 | 12.8 GI/L | Standard Deviation 29.31 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 28 | -0.13 GI/L | Standard Deviation 1.057 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 28 | -0.03 GI/L | Standard Deviation 0.08 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 42 | 0.06 GI/L | Standard Deviation 0.128 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 7 | 8.9 GI/L | Standard Deviation 18.1 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 28 | 10.8 GI/L | Standard Deviation 21.9 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 42 | -0.06 GI/L | Standard Deviation 0.12 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 7 | -0.01 GI/L | Standard Deviation 0.1 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 42 | -0.11 GI/L | Standard Deviation 0.228 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 7 | 0.11 GI/L | Standard Deviation 0.304 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 7 | -0.13 GI/L | Standard Deviation 0.666 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 7 | 0.04 GI/L | Standard Deviation 0.088 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 42 | -0.14 GI/L | Standard Deviation 0.561 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 28 | 0.0050 GI/L | Standard Deviation 0.01755 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 14 | -0.19 GI/L | Standard Deviation 0.722 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 42 | -13.2 GI/L | Standard Deviation 30.99 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 42 | 0.0019 GI/L | Standard Deviation 0.01499 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 14 | 0.04 GI/L | Standard Deviation 0.295 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 28 | -0.17 GI/L | Standard Deviation 0.778 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 14 | 0.0041 GI/L | Standard Deviation 0.01653 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 14 | -0.17 GI/L | Standard Deviation 0.862 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 42 | -0.26 GI/L | Standard Deviation 0.413 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 14 | 0.03 GI/L | Standard Deviation 0.086 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 7 | 0.0047 GI/L | Standard Deviation 0.01481 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 14 | 7.0 GI/L | Standard Deviation 11.02 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 14 | -0.04 GI/L | Standard Deviation 0.122 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 28 | 0.02 GI/L | Standard Deviation 0.083 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 28 | 0.05 GI/L | Standard Deviation 0.631 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 7 | -0.01 GI/L | Standard Deviation 0.791 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 14 | -0.27 GI/L | Standard Deviation 0.591 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 7 | 0.0047 GI/L | Standard Deviation 0.0065 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 14 | -0.0015 GI/L | Standard Deviation 0.01195 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 28 | -0.0065 GI/L | Standard Deviation 0.04654 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 42 | -0.0190 GI/L | Standard Deviation 0.04076 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 7 | -0.01 GI/L | Standard Deviation 0.055 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 14 | -0.02 GI/L | Standard Deviation 0.043 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 28 | 0.01 GI/L | Standard Deviation 0.067 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 42 | -0.02 GI/L | Standard Deviation 0.041 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 7 | 0.09 GI/L | Standard Deviation 0.253 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 14 | 0.08 GI/L | Standard Deviation 0.28 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 28 | 0.05 GI/L | Standard Deviation 0.317 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 42 | -0.11 GI/L | Standard Deviation 0.307 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 7 | 0.01 GI/L | Standard Deviation 0.149 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 14 | 0.06 GI/L | Standard Deviation 0.125 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 28 | 0.06 GI/L | Standard Deviation 0.099 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 42 | -0.00 GI/L | Standard Deviation 0.087 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 7 | -0.54 GI/L | Standard Deviation 0.5 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 28 | -0.48 GI/L | Standard Deviation 1.097 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 42 | -0.50 GI/L | Standard Deviation 0.845 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 7 | 5.0 GI/L | Standard Deviation 20.82 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 14 | 1.2 GI/L | Standard Deviation 31.94 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 28 | 0.5 GI/L | Standard Deviation 34.01 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 42 | -13.8 GI/L | Standard Deviation 41.97 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 7 | -0.43 GI/L | Standard Deviation 0.9 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 14 | -0.13 GI/L | Standard Deviation 0.933 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 28 | -0.35 GI/L | Standard Deviation 1.414 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 42 | -0.62 GI/L | Standard Deviation 1.13 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 14 | 0.06 GI/L | Standard Deviation 0.096 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 7 | 0.00 GI/L | Standard Deviation 0.115 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 28 | -0.0068 GI/L | Standard Deviation 0.02566 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 14 | 12.9 GI/L | Standard Deviation 15.97 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 42 | -0.07 GI/L | Standard Deviation 0.364 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 28 | 0.25 GI/L | Standard Deviation 0.594 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 42 | -0.22 GI/L | Standard Deviation 0.824 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 28 | 10.4 GI/L | Standard Deviation 16.91 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 14 | 0.18 GI/L | Standard Deviation 0.371 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Lymphocytes, Day 7 | 0.14 GI/L | Standard Deviation 0.511 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 28 | 0.63 GI/L | Standard Deviation 1.643 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 42 | -15.3 GI/L | Standard Deviation 28.56 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 42 | -0.01 GI/L | Standard Deviation 0.044 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 28 | -0.00 GI/L | Standard Deviation 0.079 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 14 | -0.0066 GI/L | Standard Deviation 0.01893 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 7 | 0.48 GI/L | Standard Deviation 1.099 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 14 | -0.00 GI/L | Standard Deviation 0.044 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Eosinophils, Day 7 | -0.03 GI/L | Standard Deviation 0.054 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 7 | -0.0078 GI/L | Standard Deviation 0.01673 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 28 | 0.36 GI/L | Standard Deviation 1.048 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 14 | 0.64 GI/L | Standard Deviation 0.876 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 7 | 0.38 GI/L | Standard Deviation 0.786 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | WBC count, Day 14 | 0.88 GI/L | Standard Deviation 1.131 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Total Neutrophils, Day 42 | -0.10 GI/L | Standard Deviation 0.645 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 42 | -0.03 GI/L | Standard Deviation 0.074 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Monocytes, Day 28 | 0.03 GI/L | Standard Deviation 0.132 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Basophils, Day 42 | -0.0122 GI/L | Standard Deviation 0.02336 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, WBC Count During the Double-blind Treatment Period of Part B and C | Platelet count, Day 7 | 5.8 GI/L | Standard Deviation 21.36 |
Primary
Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Monocytes, Day 28 | -0.05 Giga cells (GI)/L | Standard Deviation 0.058 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Eosinophils, Day 7 | -0.03 Giga cells (GI)/L | Standard Deviation 0.05 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Monocytes, Day 42 | -0.05 Giga cells (GI)/L | Standard Deviation 0.129 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Lymphocytes, Day 7 | -0.22 Giga cells (GI)/L | Standard Deviation 0.287 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Total Neutrophils, Day 7 | 0.15 Giga cells (GI)/L | Standard Deviation 0.947 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Basophils, Day 14 | -0.03 Giga cells (GI)/L | Standard Deviation 0.05 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Total Neutrophils, Day 14 | 0.50 Giga cells (GI)/L | Standard Deviation 0.99 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Lymphocytes, Day 14 | -0.22 Giga cells (GI)/L | Standard Deviation 0.05 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Total Neutrophils, Day 28 | -0.32 Giga cells (GI)/L | Standard Deviation 0.465 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Eosinophils, Day 14 | -0.03 Giga cells (GI)/L | Standard Deviation 0.05 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Total Neutrophils, Day 42 | 0.48 Giga cells (GI)/L | Standard Deviation 0.556 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Lymphocytes, Day 28 | -0.23 Giga cells (GI)/L | Standard Deviation 0.189 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Platelet count, Day 7 | -4.8 Giga cells (GI)/L | Standard Deviation 26.08 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Basophils, Day 42 | 0.00 Giga cells (GI)/L | Standard Deviation 0 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Platelet count, Day 14 | -14.0 Giga cells (GI)/L | Standard Deviation 45.91 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Lymphocytes, Day 42 | 0.15 Giga cells (GI)/L | Standard Deviation 0.52 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Platelet count, Day 28 | -11.5 Giga cells (GI)/L | Standard Deviation 51.98 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Eosinophils, Day 28 | 0.10 Giga cells (GI)/L | Standard Deviation 0.141 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Platelet count, Day 42 | -8.8 Giga cells (GI)/L | Standard Deviation 17.37 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Monocytes, Day 7 | -0.08 Giga cells (GI)/L | Standard Deviation 0.126 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | WBC count, Day 7 | -0.15 Giga cells (GI)/L | Standard Deviation 1.31 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Basophils, Day 28 | 0.00 Giga cells (GI)/L | Standard Deviation 0 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | WBC count, Day 14 | 0.18 Giga cells (GI)/L | Standard Deviation 0.964 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Monocytes, Day 14 | -0.10 Giga cells (GI)/L | Standard Deviation 0 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | WBC count, Day 28 | -0.50 Giga cells (GI)/L | Standard Deviation 0.49 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Eosinophils, Day 42 | 0.03 Giga cells (GI)/L | Standard Deviation 0.05 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | WBC count, Day 42 | 0.65 Giga cells (GI)/L | Standard Deviation 0.988 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Basophils, Day 7 | 0.00 Giga cells (GI)/L | Standard Deviation 0 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | WBC count, Day 42 | -0.01 Giga cells (GI)/L | Standard Deviation 0.984 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Basophils, Day 7 | 0.00 Giga cells (GI)/L | Standard Deviation 0 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Basophils, Day 14 | 0.01 Giga cells (GI)/L | Standard Deviation 0.03 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Basophils, Day 28 | 0.00 Giga cells (GI)/L | Standard Deviation 0 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Basophils, Day 42 | 0.00 Giga cells (GI)/L | Standard Deviation 0 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Eosinophils, Day 7 | -0.03 Giga cells (GI)/L | Standard Deviation 0.065 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Eosinophils, Day 14 | 0.00 Giga cells (GI)/L | Standard Deviation 0.063 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Eosinophils, Day 28 | 0.00 Giga cells (GI)/L | Standard Deviation 0.067 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Eosinophils, Day 42 | 0.00 Giga cells (GI)/L | Standard Deviation 0.094 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Lymphocytes, Day 7 | -0.01 Giga cells (GI)/L | Standard Deviation 0.644 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Lymphocytes, Day 14 | -0.06 Giga cells (GI)/L | Standard Deviation 0.448 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Lymphocytes, Day 28 | -0.32 Giga cells (GI)/L | Standard Deviation 0.496 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Lymphocytes, Day 42 | 0.05 Giga cells (GI)/L | Standard Deviation 0.264 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Monocytes, Day 7 | -0.05 Giga cells (GI)/L | Standard Deviation 0.104 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Monocytes, Day 14 | -0.05 Giga cells (GI)/L | Standard Deviation 0.069 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Monocytes, Day 28 | 0.01 Giga cells (GI)/L | Standard Deviation 0.12 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Monocytes, Day 42 | -0.06 Giga cells (GI)/L | Standard Deviation 0.052 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Total Neutrophils, Day 7 | 0.02 Giga cells (GI)/L | Standard Deviation 0.852 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Total Neutrophils, Day 14 | -0.13 Giga cells (GI)/L | Standard Deviation 0.583 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Total Neutrophils, Day 28 | 0.14 Giga cells (GI)/L | Standard Deviation 0.841 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Total Neutrophils, Day 42 | -0.01 Giga cells (GI)/L | Standard Deviation 0.743 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Platelet count, Day 7 | -1.9 Giga cells (GI)/L | Standard Deviation 16.65 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Platelet count, Day 14 | 3.8 Giga cells (GI)/L | Standard Deviation 16.3 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Platelet count, Day 28 | 9.7 Giga cells (GI)/L | Standard Deviation 29.04 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | Platelet count, Day 42 | 3.1 Giga cells (GI)/L | Standard Deviation 25.18 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | WBC count, Day 7 | -0.11 Giga cells (GI)/L | Standard Deviation 1.118 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | WBC count, Day 14 | -0.15 Giga cells (GI)/L | Standard Deviation 0.715 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, Platelet Count, White Blood Cell (WBC) Count During the Double-blind Treatment Period of Part A | WBC count, Day 28 | -0.16 Giga cells (GI)/L | Standard Deviation 1.047 |
Primary
Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 28 | 0.3 g/L | Standard Deviation 3.98 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 14 | 0.2 g/L | Standard Deviation 9.66 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 7 | -2.0 g/L | Standard Deviation 4.82 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 42 | 2.0 g/L | Standard Deviation 6.16 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 42 | 0.0 g/L | Standard Deviation 2.97 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 7 | 0.2 g/L | Standard Deviation 5.08 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 14 | 2.0 g/L | Standard Deviation 7.21 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 28 | 1.7 g/L | Standard Deviation 7.15 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 14 | -3.8 g/L | Standard Deviation 5.28 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 42 | 0.2 g/L | Standard Deviation 4.36 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 28 | -1.9 g/L | Standard Deviation 4.8 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 42 | -0.8 g/L | Standard Deviation 4.87 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 7 | -1.0 g/L | Standard Deviation 4.67 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 7 | -4.1 g/L | Standard Deviation 5.4 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 28 | -1.1 g/L | Standard Deviation 7.63 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 14 | -1.1 g/L | Standard Deviation 6.5 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 14 | -1.2 g/L | Standard Deviation 3.54 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 28 | -1.2 g/L | Standard Deviation 8.68 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 42 | -2.8 g/L | Standard Deviation 4.58 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 7 | -4.5 g/L | Standard Deviation 2.74 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 14 | 1.7 g/L | Standard Deviation 4.93 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 28 | -2.0 g/L | Standard Deviation 5.22 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 42 | -0.2 g/L | Standard Deviation 2.79 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 7 | -4.3 g/L | Standard Deviation 5.85 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 28 | -0.3 g/L | Standard Deviation 8.7 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 42 | 0.8 g/L | Standard Deviation 4.63 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 7 | -2.8 g/L | Standard Deviation 4.97 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 42 | -4.8 g/L | Standard Deviation 5.83 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 14 | -2.1 g/L | Standard Deviation 13.1 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | Hemoglobin, Day 7 | -3.4 g/L | Standard Deviation 6.89 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 28 | -1.4 g/L | Standard Deviation 3.53 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of Hemoglobin and MCHC During the Double-blind Treatment Period of Part B and C | MCHC, Day 14 | -2.6 g/L | Standard Deviation 5.09 |
Primary
Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Hemoglobin, Day 7 | 0.8 g/L | Standard Deviation 2.06 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Hemoglobin, Day 14 | 4.0 g/L | Standard Deviation 4.24 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Hemoglobin, Day 28 | 11.3 g/L | Standard Deviation 7.41 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Hemoglobin, Day 42 | 9.8 g/L | Standard Deviation 7.37 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | MCHC, Day 7 | 1.8 g/L | Standard Deviation 2.99 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | MCHC, Day 14 | -0.5 g/L | Standard Deviation 9.4 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | MCHC, Day 28 | 8.5 g/L | Standard Deviation 7.55 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | MCHC, Day 42 | 17.5 g/L | Standard Deviation 7.19 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | MCHC, Day 42 | 9.0 g/L | Standard Deviation 11.75 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Hemoglobin, Day 7 | -2.0 g/L | Standard Deviation 6.36 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | MCHC, Day 7 | 5.4 g/L | Standard Deviation 7.31 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Hemoglobin, Day 14 | -0.9 g/L | Standard Deviation 7.3 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | MCHC, Day 28 | 6.3 g/L | Standard Deviation 6.02 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Hemoglobin, Day 28 | 0.5 g/L | Standard Deviation 3.84 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | MCHC, Day 14 | 0.0 g/L | Standard Deviation 5.71 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Hemoglobin and Mean Corpuscle Hemoglobin Concentration (MCHC) During the Double-blind Treatment Period of Part A | Hemoglobin, Day 42 | 0.9 g/L | Standard Deviation 9.34 |
Primary
Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 7 | 0.018 TI/L | Standard Deviation 0.1916 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 14 | -0.030 TI/L | Standard Deviation 0.2999 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 28 | 0.002 TI/L | Standard Deviation 0.1229 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 42 | 0.032 TI/L | Standard Deviation 0.0662 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 7 | 0.0020 TI/L | Standard Deviation 0.01123 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 14 | -0.0019 TI/L | Standard Deviation 0.02127 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 28 | 0.0029 TI/L | Standard Deviation 0.01673 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 42 | 0.0062 TI/L | Standard Deviation 0.01283 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 14 | 0.0095 TI/L | Standard Deviation 0.02126 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 7 | -0.0003 TI/L | Standard Deviation 0.01284 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 14 | -0.011 TI/L | Standard Deviation 0.2282 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 42 | 0.0096 TI/L | Standard Deviation 0.01916 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 28 | 0.0035 TI/L | Standard Deviation 0.01697 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 42 | -0.031 TI/L | Standard Deviation 0.1445 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 28 | -0.023 TI/L | Standard Deviation 0.25 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 7 | 0.004 TI/L | Standard Deviation 0.1536 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 28 | -0.0304 TI/L | Standard Deviation 0.01024 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 28 | 0.020 TI/L | Standard Deviation 0.3651 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 42 | -0.053 TI/L | Standard Deviation 0.1978 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 7 | -0.0210 TI/L | Standard Deviation 0.02605 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 14 | -0.0286 TI/L | Standard Deviation 0.02354 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 42 | -0.0200 TI/L | Standard Deviation 0.03679 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 7 | -0.107 TI/L | Standard Deviation 0.2013 |
| Part C-Placebo+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 14 | 0.093 TI/L | Standard Deviation 0.2399 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 28 | -0.003 TI/L | Standard Deviation 0.2871 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 42 | -0.168 TI/L | Standard Deviation 0.1987 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 14 | -0.072 TI/L | Standard Deviation 0.4808 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | RBC count, Day 7 | -0.085 TI/L | Standard Deviation 0.2176 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 7 | -0.0015 TI/L | Standard Deviation 0.02719 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 42 | -0.0042 TI/L | Standard Deviation 0.02667 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 28 | -0.0052 TI/L | Standard Deviation 0.01674 |
| Part C-GSK2890457+Metformin | Change From Baseline in Hematology Parameters of RBC Count and Reticulocytes During the Double-blind Treatment Period of Part B and C | Reticulocytes, Day 14 | 0.0147 TI/L | Standard Deviation 0.02091 |
Primary
Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | RBC count, Day 7 | -0.008 Trillion cells (TI)/L | Standard Deviation 0.1014 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | RBC count, Day 14 | 0.090 Trillion cells (TI)/L | Standard Deviation 0.0337 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | RBC count, Day 28 | 0.258 Trillion cells (TI)/L | Standard Deviation 0.1455 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | RBC count, Day 42 | 0.107 Trillion cells (TI)/L | Standard Deviation 0.3192 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Reticulocytes, Day 7 | 0.0115 Trillion cells (TI)/L | Standard Deviation 0.00281 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Reticulocytes, Day 14 | 0.0077 Trillion cells (TI)/L | Standard Deviation 0.00189 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Reticulocytes, Day 28 | 0.0073 Trillion cells (TI)/L | Standard Deviation 0.00151 |
| Part A-Placebo | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Reticulocytes, Day 42 | 0.0022 Trillion cells (TI)/L | Standard Deviation 0.00998 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Reticulocytes, Day 42 | 0.0044 Trillion cells (TI)/L | Standard Deviation 0.01396 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | RBC count, Day 7 | -0.116 Trillion cells (TI)/L | Standard Deviation 0.1851 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Reticulocytes, Day 7 | 0.0014 Trillion cells (TI)/L | Standard Deviation 0.01076 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | RBC count, Day 14 | -0.084 Trillion cells (TI)/L | Standard Deviation 0.2313 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Reticulocytes, Day 28 | 0.0071 Trillion cells (TI)/L | Standard Deviation 0.01522 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | RBC count, Day 28 | -0.045 Trillion cells (TI)/L | Standard Deviation 0.1516 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | Reticulocytes, Day 14 | -0.0017 Trillion cells (TI)/L | Standard Deviation 0.01001 |
| Part A-GSK2890457 | Change From Baseline in Hematology Parameters of Red Blood Cell (RBC) Count and Reticulocytes During the Double-blind Treatment Period of Part A | RBC count, Day 42 | -0.115 Trillion cells (TI)/L | Standard Deviation 0.2632 |
Primary
Change From Baseline in Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR]) During the Double-blind Treatment Period of Part B and C
HOMA-IR was calculated from the Day -1 and Day 42 fasting glucose and insulin values using dataset generated from the HOMA-2 model. It contained the estimates for HOMA-% insulin sensitivity (S) for pairs of fasting glucose and fasting insulin values. Study data was merged with the HOMA dataset by glucose and insulin. HOMA-IR was calculated as 100/HOMA-%S. HOMA-IR was not determined for any values outside the ranges of plasma glucose 3.5 to 25.0 mmol/L (63 - 450 mg/dL) and plasma insulin 20 to 400 pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.
Time frame: Baseline (Day -1) and Day 42
Population: PD Population. Only those participants available at the specified time points were analyzed. Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A-Placebo | Change From Baseline in Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR]) During the Double-blind Treatment Period of Part B and C | -0.150 mU*mmol/L^2 | Standard Deviation 0.497 |
| Part A-GSK2890457 | Change From Baseline in Homeostasis Model of Assessment-Insulin Resistance (HOMA-IR]) During the Double-blind Treatment Period of Part B and C | 0.017 mU*mmol/L^2 | Standard Deviation 0.7222 |
Primary
Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C
During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values.
Time frame: Baseline (Day -1 and Day 1) up to Day 42
Population: Pharmacodynamic (PD) Population comprised of all participants in the All Subjects Population who had Baseline and at least one post-Baseline assessment of the endpoint. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 42 | -0.74 Kilograms (kg) | Standard Deviation 1.02 |
| Part A-Placebo | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 28 | 0.15 Kilograms (kg) | Standard Deviation 1.161 |
| Part A-Placebo | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 7 | -0.12 Kilograms (kg) | Standard Deviation 0.938 |
| Part A-Placebo | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 14 | 0.37 Kilograms (kg) | Standard Deviation 1.157 |
| Part A-GSK2890457 | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 14 | 0.05 Kilograms (kg) | Standard Deviation 1.292 |
| Part A-GSK2890457 | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 7 | 0.20 Kilograms (kg) | Standard Deviation 1.368 |
| Part A-GSK2890457 | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 28 | 0.47 Kilograms (kg) | Standard Deviation 1.627 |
| Part A-GSK2890457 | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 42 | -0.39 Kilograms (kg) | Standard Deviation 1.687 |
| Part C-Placebo+Metformin | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 28 | 0.52 Kilograms (kg) | Standard Deviation 0.612 |
| Part C-Placebo+Metformin | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 42 | -0.47 Kilograms (kg) | Standard Deviation 1.104 |
| Part C-Placebo+Metformin | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 14 | 0.61 Kilograms (kg) | Standard Deviation 1.009 |
| Part C-Placebo+Metformin | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 7 | 0.28 Kilograms (kg) | Standard Deviation 0.579 |
| Part C-GSK2890457+Metformin | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 42 | 0.42 Kilograms (kg) | Standard Deviation 1.221 |
| Part C-GSK2890457+Metformin | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 7 | 0.47 Kilograms (kg) | Standard Deviation 0.84 |
| Part C-GSK2890457+Metformin | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 14 | 0.56 Kilograms (kg) | Standard Deviation 0.779 |
| Part C-GSK2890457+Metformin | Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 28 | 0.27 Kilograms (kg) | Standard Deviation 1.265 |
Comparison: Part B-Placebo+Liraglutide versus Part B-GSK2890457+Liraglutide for Day 42 change from Baseline in body weight.95% CI: [-1.38, 1.75]ANCOVA
Comparison: Part C-Placebo+Metformin versus Part C-GSK2890457+Metformin for Day 42 change from Baseline in body weight.95% CI: [-0.2, 2.36]ANCOVA
Primary
Change From Baseline in Matsuda Index During the Double Blind-treatment Period of Part B and C
The matsuda index was calculated from the Day -1 and Day 42 glucose and insulin results as 10,000 divided by (fasting plasma glucose x fasting plasma insulin x mean glucose at 0-2 hour post-dose x mean insulin at 0-2 hour post dose)\^1/2, where glucose was measured in mmol/L and insulin in pmol/L. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.
Time frame: Baseline (Day -1) and Day 42
Population: PD Population. Only those participants available at the specified time points were analyzed. Data for Part C of the study was not collected because fasting glucose and insulin were not available at the specified time points.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A-Placebo | Change From Baseline in Matsuda Index During the Double Blind-treatment Period of Part B and C | -0.991 Deciliter*mL/mg*mU | Standard Deviation 0.6904 |
| Part A-GSK2890457 | Change From Baseline in Matsuda Index During the Double Blind-treatment Period of Part B and C | -0.602 Deciliter*mL/mg*mU | Standard Deviation 2.4187 |
Primary
Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A
The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14 and 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A | Day 7 | 0.02 Scores on scale | Standard Deviation 0.033 |
| Part A-Placebo | Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A | Day 14 | 0.08 Scores on scale | Standard Deviation 0.1 |
| Part A-Placebo | Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A | Day 42 | 0.02 Scores on scale | Standard Deviation 0.033 |
| Part A-GSK2890457 | Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A | Day 7 | 0.08 Scores on scale | Standard Deviation 0.12 |
| Part A-GSK2890457 | Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A | Day 14 | 0.04 Scores on scale | Standard Deviation 0.105 |
| Part A-GSK2890457 | Change From Baseline in the Overall Gastrointestinal (GI) Symptoms Rating Scale (GSRS) Score During the Double-blind Treatment Period of Part A | Day 42 | -0.02 Scores on scale | Standard Deviation 0.071 |
Primary
Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C
The impact of GI symptoms on health-related quality of life was assessed using the GSRS. The GSRS is a 15-item related to abdominal pain, reflux, indigestion, diarrhea and constipation syndromes, self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort). Overall GSRS was the mean of items 1 to 15. Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to GI symptoms and higher scores indicating a lower quality of life with respect to GI symptoms. Baseline was defined as the assessment done on Day -2. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, 14, 28 and 41) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -2) up to Day 41
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 7 | 0.03 Scores on scale | Standard Deviation 0.516 |
| Part A-Placebo | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 14 | -0.09 Scores on scale | Standard Deviation 0.167 |
| Part A-Placebo | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 28 | -0.21 Scores on scale | Standard Deviation 0.191 |
| Part A-Placebo | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 41 | -0.11 Scores on scale | Standard Deviation 0.259 |
| Part A-GSK2890457 | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 14 | 0.05 Scores on scale | Standard Deviation 0.44 |
| Part A-GSK2890457 | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 28 | 0.03 Scores on scale | Standard Deviation 0.428 |
| Part A-GSK2890457 | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 41 | -0.12 Scores on scale | Standard Deviation 0.29 |
| Part A-GSK2890457 | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 7 | -0.03 Scores on scale | Standard Deviation 0.473 |
| Part C-Placebo+Metformin | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 28 | 0.14 Scores on scale | Standard Deviation 0.281 |
| Part C-Placebo+Metformin | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 14 | 0.20 Scores on scale | Standard Deviation 0.386 |
| Part C-Placebo+Metformin | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 41 | 0.02 Scores on scale | Standard Deviation 0.091 |
| Part C-Placebo+Metformin | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 7 | 0.24 Scores on scale | Standard Deviation 0.397 |
| Part C-GSK2890457+Metformin | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 41 | 0.10 Scores on scale | Standard Deviation 0.325 |
| Part C-GSK2890457+Metformin | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 14 | 0.28 Scores on scale | Standard Deviation 0.366 |
| Part C-GSK2890457+Metformin | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 7 | 0.13 Scores on scale | Standard Deviation 0.197 |
| Part C-GSK2890457+Metformin | Change From Baseline in the Overall GSRS Score During the Double-blind Treatment Period of Part B and C | Day 28 | 0.27 Scores on scale | Standard Deviation 0.436 |
Primary
Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A
Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Day 7 | 8.0 Beats per minute | Standard Deviation 6.83 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Day 14 | 6.3 Beats per minute | Standard Deviation 7.27 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Day 28 | 5.5 Beats per minute | Standard Deviation 9.57 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Day 42 | -1.3 Beats per minute | Standard Deviation 7.37 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Day 42 | -4.4 Beats per minute | Standard Deviation 6.29 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Day 7 | 4.6 Beats per minute | Standard Deviation 6.13 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Day 28 | 3.3 Beats per minute | Standard Deviation 7.07 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Heart Rate (HR) During the Double-blind Treatment Period of Part A | Day 14 | 0.6 Beats per minute | Standard Deviation 6.75 |
Primary
Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C
Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 7 | -3.6 Beats per minute | Standard Deviation 6.37 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 14 | -3.3 Beats per minute | Standard Deviation 6.65 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 28 | -7.8 Beats per minute | Standard Deviation 7.37 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 42 | -4.8 Beats per minute | Standard Deviation 4.45 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 14 | 0.4 Beats per minute | Standard Deviation 7.65 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 28 | 3.7 Beats per minute | Standard Deviation 7.92 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 42 | 1.6 Beats per minute | Standard Deviation 7.42 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 7 | 0.3 Beats per minute | Standard Deviation 7.91 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 28 | 1.8 Beats per minute | Standard Deviation 4.98 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 14 | 0.8 Beats per minute | Standard Deviation 7.71 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 42 | -3.2 Beats per minute | Standard Deviation 5.85 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 7 | 0.1 Beats per minute | Standard Deviation 5.9 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 42 | 0.5 Beats per minute | Standard Deviation 4.75 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 14 | 3.6 Beats per minute | Standard Deviation 5.72 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 7 | 1.6 Beats per minute | Standard Deviation 6.81 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of HR During the Double-blind Treatment Period of Part B and C | Day 28 | 1.5 Beats per minute | Standard Deviation 8.7 |
Primary
Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C
Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day -1) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 7 | 1.6 mmHg | Standard Deviation 11.11 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 14 | 5.6 mmHg | Standard Deviation 9.7 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 28 | -0.6 mmHg | Standard Deviation 7.43 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 42 | -2.6 mmHg | Standard Deviation 6.18 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 7 | -2.4 mmHg | Standard Deviation 6 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 14 | 2.1 mmHg | Standard Deviation 6.87 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 28 | -3.3 mmHg | Standard Deviation 3.96 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 42 | -1.5 mmHg | Standard Deviation 4.6 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 14 | 0.8 mmHg | Standard Deviation 3.23 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 7 | 0.4 mmHg | Standard Deviation 4.88 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 14 | 3.6 mmHg | Standard Deviation 8.52 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 42 | 0.8 mmHg | Standard Deviation 4.32 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 28 | 0.4 mmHg | Standard Deviation 5.33 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 42 | 0.1 mmHg | Standard Deviation 4.31 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 28 | 0.2 mmHg | Standard Deviation 9.51 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 7 | 2.0 mmHg | Standard Deviation 11.05 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 28 | -0.4 mmHg | Standard Deviation 6.06 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 28 | 4.5 mmHg | Standard Deviation 13.29 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 42 | 0.0 mmHg | Standard Deviation 10.11 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 7 | 0.9 mmHg | Standard Deviation 4.53 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 14 | -0.8 mmHg | Standard Deviation 2.42 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 42 | 1.1 mmHg | Standard Deviation 4.35 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 7 | 3.2 mmHg | Standard Deviation 6.94 |
| Part C-Placebo+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 14 | 3.2 mmHg | Standard Deviation 9.28 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 28 | -7.4 mmHg | Standard Deviation 9.62 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 42 | -3.0 mmHg | Standard Deviation 10.04 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 14 | -2.8 mmHg | Standard Deviation 9.45 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | SBP, Day 7 | -3.7 mmHg | Standard Deviation 12.4 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 7 | -0.8 mmHg | Standard Deviation 5.71 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 42 | -3.2 mmHg | Standard Deviation 5.3 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 28 | -3.4 mmHg | Standard Deviation 5.33 |
| Part C-GSK2890457+Metformin | Change From Baseline in Vital Sign Parameter of SBP and DBP During the Double-blind Treatment Period of Part B and C | DBP, Day 14 | -2.5 mmHg | Standard Deviation 5.7 |
Primary
Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A
Vital sign assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Baseline value was defined as the assessment done on Day 1. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing.
Time frame: Baseline (Day 1, Randomization) up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | SBP, Day 7 | 0.8 Millimeters of mercury (mmHg) | Standard Deviation 11.7 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | SBP, Day 14 | -0.5 Millimeters of mercury (mmHg) | Standard Deviation 1.91 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | SBP, Day 28 | -3.3 Millimeters of mercury (mmHg) | Standard Deviation 6.45 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | SBP, Day 42 | -1.0 Millimeters of mercury (mmHg) | Standard Deviation 11.28 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | DBP, Day 7 | -5.3 Millimeters of mercury (mmHg) | Standard Deviation 4.5 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | DBP, Day 14 | -1.8 Millimeters of mercury (mmHg) | Standard Deviation 3.95 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | DBP, Day 28 | -1.3 Millimeters of mercury (mmHg) | Standard Deviation 5.56 |
| Part A-Placebo | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | DBP, Day 42 | -0.8 Millimeters of mercury (mmHg) | Standard Deviation 3.3 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | DBP, Day 42 | -6.4 Millimeters of mercury (mmHg) | Standard Deviation 7.21 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | SBP, Day 7 | -4.0 Millimeters of mercury (mmHg) | Standard Deviation 4.94 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | DBP, Day 7 | -6.2 Millimeters of mercury (mmHg) | Standard Deviation 4.12 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | SBP, Day 14 | -3.9 Millimeters of mercury (mmHg) | Standard Deviation 6.45 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | DBP, Day 28 | -8.4 Millimeters of mercury (mmHg) | Standard Deviation 5.72 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | SBP, Day 28 | -5.5 Millimeters of mercury (mmHg) | Standard Deviation 7.55 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | DBP, Day 14 | -5.0 Millimeters of mercury (mmHg) | Standard Deviation 8.51 |
| Part A-GSK2890457 | Change From Baseline in Vital Sign Parameter of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) During the Double-blind Treatment Period of Part A | SBP, Day 42 | -7.5 Millimeters of mercury (mmHg) | Standard Deviation 6.19 |
Primary
Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C
AUC was calculated using the linear trapezoid method that is the sum of the areas between each chronological pair of assessments at the time points (at Day -1 and Day 42). The weighted mean was then calculated by dividing the AUC by the length of the time interval over which it was calculated. Baseline was defined as the assessment done on Day -1. Change from Baseline was calculated by subtracting the Baseline (Day -1) values from the post-Baseline value (Day 42). Data is reported for weighted mean glucose AUC (0-4 hour) post-breakfast and AUC (0-24 hour) post-breakfast. Adjusted mean is reported as least square (LS) mean.
Time frame: Baseline (Day -1) and Day 42
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | AUC (0-4 hour) | 0.018 mmol/L | Standard Error 0.583 |
| Part A-Placebo | Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | AUC (0-24 hour) | -0.613 mmol/L | Standard Error 0.41 |
| Part A-GSK2890457 | Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | AUC (0-24 hour) | -0.968 mmol/L | Standard Error 0.278 |
| Part A-GSK2890457 | Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | AUC (0-4 hour) | -0.164 mmol/L | Standard Error 0.39 |
| Part C-Placebo+Metformin | Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | AUC (0-4 hour) | 1.194 mmol/L | Standard Error 0.518 |
| Part C-Placebo+Metformin | Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | AUC (0-24 hour) | 1.376 mmol/L | Standard Error 0.459 |
| Part C-GSK2890457+Metformin | Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | AUC (0-4 hour) | 0.341 mmol/L | Standard Error 0.359 |
| Part C-GSK2890457+Metformin | Change From Baseline in Weighted Mean Glucose Area Under the Curves From Time 0 to 24 Hours (AUC [0-24 Hours]) During the Double-blind Treatment Period of Part B and C | AUC (0-24 hour) | 0.156 mmol/L | Standard Error 0.316 |
Comparison: Part B-Placebo+Liraglutide versus Part B-GSK2890457+Liraglutide for Day 42 change from Baseline in AUC (0-4 hour) weighted mean glucose.95% CI: [-1.694, 1.331]ANCOVA
Comparison: Part B-Placebo+Liraglutide versus Part B-GSK2890457+Liraglutide for Day 42 change from Baseline in AUC (0-24 hour) weighted mean glucose.95% CI: [-1.409, 0.698]ANCOVA
Comparison: Part C-Placebo+Metformin versus Part C-GSK2890457+Metformin for Day 42 change from Baseline in AUC (0-4 hour) weighted mean glucose.95% CI: [-2.232, 0.526]ANCOVA
Comparison: Part C-Placebo+Metformin versus Part C-GSK2890457+Metformin for Day 42 change from Baseline in AUC (0-24 hour) weighted mean glucose.95% CI: [-2.447, 0.009]ANCOVA
Primary
Mean pH Values of Urine During the Double-blind Treatment Period of Part A
Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day 1, Day 7, Day 14, Day 28 and Day 42.
Time frame: up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 7 | 5.88 pH | Standard Deviation 0.854 |
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 28 | 6.13 pH | Standard Deviation 1.031 |
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 14 | 5.50 pH | Standard Deviation 0.408 |
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 42 | 5.63 pH | Standard Deviation 0.25 |
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 1 | 5.25 pH | Standard Deviation 0.289 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 42 | 6.20 pH | Standard Deviation 0.632 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 1 | 5.95 pH | Standard Deviation 0.472 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 7 | 5.86 pH | Standard Deviation 0.745 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 14 | 5.91 pH | Standard Deviation 0.735 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part A | Day 28 | 6.05 pH | Standard Deviation 0.832 |
Primary
Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C
Urinalysis parameter included urine pH. pH was calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral. The assessments were done pre-dose on Day -1, Day 7, Day 14, Day 28 and Day 42.
Time frame: Up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 28 | 5.75 pH | Standard Deviation 0.418 |
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 7 | 5.83 pH | Standard Deviation 0.683 |
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 42 | 6.00 pH | Standard Deviation 0.316 |
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 14 | 5.67 pH | Standard Deviation 0.408 |
| Part A-Placebo | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day -1 | 5.92 pH | Standard Deviation 0.376 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 14 | 6.07 pH | Standard Deviation 0.646 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 28 | 5.96 pH | Standard Deviation 0.477 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 42 | 6.08 pH | Standard Deviation 0.449 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 7 | 5.89 pH | Standard Deviation 0.35 |
| Part A-GSK2890457 | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day -1 | 6.25 pH | Standard Deviation 0.47 |
| Part C-Placebo+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 14 | 5.67 pH | Standard Deviation 0.516 |
| Part C-Placebo+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day -1 | 5.67 pH | Standard Deviation 0.408 |
| Part C-Placebo+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 7 | 5.83 pH | Standard Deviation 0.816 |
| Part C-Placebo+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 28 | 5.67 pH | Standard Deviation 0.408 |
| Part C-Placebo+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 42 | 5.58 pH | Standard Deviation 0.376 |
| Part C-GSK2890457+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 28 | 5.63 pH | Standard Deviation 0.311 |
| Part C-GSK2890457+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 7 | 5.42 pH | Standard Deviation 0.359 |
| Part C-GSK2890457+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day -1 | 5.83 pH | Standard Deviation 0.537 |
| Part C-GSK2890457+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 14 | 5.63 pH | Standard Deviation 0.433 |
| Part C-GSK2890457+Metformin | Mean pH Values of Urine During the Double-blind Treatment Period of Part B and C | Day 42 | 5.58 pH | Standard Deviation 0.417 |
Primary
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A
Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Da y 1, Day 7, Day 14, Day 28 and Day 42.
Time frame: Up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 7 | 1.0133 Ratio | Standard Deviation 0.00685 |
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 28 | 1.0125 Ratio | Standard Deviation 0.00705 |
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 14 | 1.0153 Ratio | Standard Deviation 0.00591 |
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 42 | 1.0155 Ratio | Standard Deviation 0.00759 |
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 1 | 1.0193 Ratio | Standard Deviation 0.00903 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 42 | 1.0161 Ratio | Standard Deviation 0.00827 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 1 | 1.0175 Ratio | Standard Deviation 0.00794 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 7 | 1.0165 Ratio | Standard Deviation 0.00887 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 14 | 1.0152 Ratio | Standard Deviation 0.00752 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part A | Day 28 | 1.0122 Ratio | Standard Deviation 0.00983 |
Primary
Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C
Urinary specific gravity is a measure of the concentration of solutes in urine. It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine. The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42.
Time frame: Up to Day 42
Population: All Subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 28 | 1.0232 Ratio | Standard Deviation 0.00906 |
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 7 | 1.0208 Ratio | Standard Deviation 0.00794 |
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 42 | 1.0137 Ratio | Standard Deviation 0.00535 |
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 14 | 1.0202 Ratio | Standard Deviation 0.00861 |
| Part A-Placebo | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day -1 | 1.0168 Ratio | Standard Deviation 0.00773 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 14 | 1.0196 Ratio | Standard Deviation 0.00812 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 28 | 1.0239 Ratio | Standard Deviation 0.00533 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 42 | 1.0188 Ratio | Standard Deviation 0.0091 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 7 | 1.0191 Ratio | Standard Deviation 0.00734 |
| Part A-GSK2890457 | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day -1 | 1.0174 Ratio | Standard Deviation 0.00482 |
| Part C-Placebo+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 14 | 1.0198 Ratio | Standard Deviation 0.00382 |
| Part C-Placebo+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day -1 | 1.0172 Ratio | Standard Deviation 0.00627 |
| Part C-Placebo+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 7 | 1.0197 Ratio | Standard Deviation 0.00356 |
| Part C-Placebo+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 28 | 1.0213 Ratio | Standard Deviation 0.00505 |
| Part C-Placebo+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 42 | 1.0110 Ratio | Standard Deviation 0.00544 |
| Part C-GSK2890457+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 28 | 1.0213 Ratio | Standard Deviation 0.00559 |
| Part C-GSK2890457+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 7 | 1.0208 Ratio | Standard Deviation 0.00688 |
| Part C-GSK2890457+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day -1 | 1.0187 Ratio | Standard Deviation 0.00796 |
| Part C-GSK2890457+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 14 | 1.0201 Ratio | Standard Deviation 0.00629 |
| Part C-GSK2890457+Metformin | Mean Specific Gravity Values of Urine During the Double-blind Treatment Period of Part B and C | Day 42 | 1.0172 Ratio | Standard Deviation 0.01021 |
Primary
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A
The assessments were done pre-dose at Day 1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as rare, trace, +1, 2+, RBC's and WBC's as \<1, 1, 2, 3 and 4. Protein concentration ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. Trace was the highest concentration for occult blood. Bacteria concentration ranged from rare to moderate, where rare indicated lowest concentration and moderate indicated highest concentration. Ketones ranged from trace to 1+, where trace indicated lowest concentration and 1+ indicated highest concentration. RBC and WBC ranged from \<1 to 4, where \<1 indicated lowest concentration and 4 indicated highest concentration. Highest concentration indicated worse outcome.
Time frame: Up to Day 42
Population: All Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Occult blood, Trace, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, 1+, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 42 | 2 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Bacteria, Rare, Day 1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Bacteria, Rare, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Bacteria, Moderate, Day 42 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Occult blood, Trace, Day 1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Occult blood, Trace, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, 1+, Day 1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, 1+, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, Trace, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, Trace, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, Trace, Day 42 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 1, Day 1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 3, Day 1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 1, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 2, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 1, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 28 | 2 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 1, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 2, Day 42 | 2 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 1, Day 1 | 2 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, <1, Day 1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 1, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, <1, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 2, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, <1, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 1, Day 28 | 2 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, <1, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 1, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 2, Day 42 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 4, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 1, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 1 | 3 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 1, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 7 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, <1, Day 1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, 1+, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 1, Day 28 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 28 | 4 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 2, Day 14 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Protein, Trace, Day 42 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 1, Day 7 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Bacteria, Rare, Day 1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 14 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Bacteria, Rare, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 4, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Bacteria, Moderate, Day 42 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 1, Day 28 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Occult blood, Trace, Day 1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, <1, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Occult blood, Trace, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 28 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Occult blood, Trace, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, <1, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, 1+, Day 1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 1, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, 1+, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 2, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, Trace, Day 14 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 2, Day 42 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, Trace, Day 28 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 2, Day 42 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | Ketones, Trace, Day 42 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 1, Day 1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, <1, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, 3, Day 1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | WBC's, 1, Day 1 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part A | RBC's, <1, Day 1 | 1 Participants |
Primary
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. Only those parameters for which at least one value of abnormal urinalysis result was reported are summarized. The participants were categorized as few, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, and 20-40. Few was the highest concentration of bacteria. Occult blood ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Epithelial cell ranged from 0-5 to 10-20, 0-5 indicated lowest and 10-20 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-5 was highest concentration for hyaline casts. Ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. RBC and WBC ranged from 0-3 to 20-40, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome.
Time frame: Up to Day 42
Population: All Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day -1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Occult Blood, 1+, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Occult Blood, Trace, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Occult Blood, Trace, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 10-20, Day -1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 0-5, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 6-10, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 0-5, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 0-5, Day 42 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day -1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Bacteria, Few, Day -1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day -1 | 2 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 2+, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 2+, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day 42 | 2 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 2+, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day 42 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Hyaline Casts, 0-5, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Ketones, 1+, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Ketones, Trace, Day 14 | 2 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Ketones, Trace, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day-1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 20-40, Day -1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 0-5, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 6-10, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 0-5, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 0-5, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 0-5, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day-1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Bacteria, Few, Day -1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day 28 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Occult Blood, 1+, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 0-5, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Occult Blood, Trace, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Occult Blood, Trace, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day 7 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 10-20, Day -1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day 42 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 0-5, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 0-5, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 6-10, Day 7 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 2+, Day 42 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 0-5, Day 14 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Epithelial Cells, 0-5, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day 42 | 3 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day -1 | 4 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 0-5, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day -1 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day 42 | 3 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day -1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Hyaline Casts, 0-5, Day 14 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day 7 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 6-10, Day 7 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day 7 | 3 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Ketones, 1+, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | RBC's, 0-3, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 2+, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Ketones, Trace, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 3+, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 0-5, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, Trace, Day 14 | 3 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Ketones, Trace, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 1+, Day 28 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | WBC's, 20-40, Day -1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part B | Glucose, 2+, Day 28 | 1 Participants |
Primary
Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C
The assessments were done pre-dose at Day -1, Day 7, Day 14, Day 28 and Day 42. The participants were categorized as few, many, moderate, trace, +1, 2+, 3+, 0-3, 10-20, 0-5, 6-10, 20-40, 40-60. Protein and ketone ranged from trace to 1+, trace indicated lowest and 1+ indicated highest concentration. Bacteria and uric acid crystals ranged from few to moderate, few indicated lowest and moderate indicated highest concentration. Trace was the highest concentration of occult blood. Epithelial cells ranged from 0-5 to \>10, 0-5 indicated lowest and \>10 indicated highest concentration. Glucose ranged from trace to 3+, trace indicated lowest and 3+ indicated highest concentration. 0-1 was highest concentration for hyaline casts. RBC and WBC ranged from 0-3 to 40-60, 0-3 indicated lowest and 20-40 indicated highest concentration. Highest concentration indicated worse outcome.
Time frame: Up to Day 42
Population: All Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-10, Day -1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 1+, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-10, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, Trace, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Protein, Trace, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 2+, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-5, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Moderate, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, Trace, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 6-10, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 1+, Day 42 | 3 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day -1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 2+, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-5, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Few, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, Trace, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, >10, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Hyaline Casts, 0-1, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Protein, 1+, Day 28 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Ketones, 1+, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-10, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Ketones, Trace, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Ketones, Trace, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-10, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Ketones, Trace, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Few, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day -1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 1+, Day -1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day 42 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 2+, Day -1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Protein, Trace, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day -1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Uric acid crystals, Moderate, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Moderate, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Uric acid crystals, Few, Day 14 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 1+, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 0-5, Day -1 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 0-5, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 2+, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 6-10, Day 7 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Occult Blood, Trace, Day 42 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 0-5, Day 14 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 0-5, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Few, Day -1 | 0 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 40-60, Day 28 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, Trace, Day 7 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 6-10, Day 42 | 1 Participants |
| Part A-Placebo | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Protein, 1+, Day 7 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 6-10, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Protein, 1+, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Protein, Trace, Day 7 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Protein, Trace, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Protein, 1+, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Few, Day -1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day -1 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Few, Day 7 | 4 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day 7 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Moderate, Day 14 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Few, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day 28 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Many, Day 42 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Bacteria, Moderate, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Occult Blood, Trace, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-10, Day -1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-10, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-5, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 6-10, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-5, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, >10, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-10, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Epithelial Cells, 0-10, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 1+, Day -1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 2+, Day -1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day -1 | 6 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 1+, Day 7 | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 2+, Day 7 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, Trace, Day 7 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 1+, Day 14 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day 14 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, Trace, Day 14 | 4 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 2+, Day 28 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, Trace, Day 28 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 1+, Day 42 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 2+, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, 3+, Day 42 | 4 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Glucose, Trace, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Hyaline Casts, 0-1, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Ketones, 1+, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Ketones, Trace, Day 7 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Ketones, Trace, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Ketones, Trace, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day -1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day 7 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day 14 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | RBC's, 0-3, Day 42 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Uric acid crystals, Moderate, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | Uric acid crystals, Few, Day 14 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 0-5, Day -1 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 0-5, Day 7 | 3 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 6-10, Day 7 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 0-5, Day 14 | 2 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 0-5, Day 28 | 1 Participants |
| Part A-GSK2890457 | Number of Participants With Abnormal Urinalyisis Dipstick and Microscopic Results During the Double-blind Treatment Period of Part C | WBC's, 40-60, Day 28 | 0 Participants |
Primary
Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) \>=3 x upper limit of normal (ULN), and total bilirubin \>=2 x ULN or international normalized ratio \>1.5.
Time frame: Up to Follow-up (8 weeks)
Population: All Subjects Population comprised of all randomized participants who received at least one dose of study medication (placebo or GSK2890457).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Placebo | Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A | Any AE | 3 Participants |
| Part A-Placebo | Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A | Any SAE | 0 Participants |
| Part A-Placebo | Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A | Any Death | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A | Any AE | 10 Participants |
| Part A-GSK2890457 | Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A | Any SAE | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Any Adverse Event (AE), Serious Adverse Event (SAE) or Death During Part A | Any Death | 0 Participants |
Primary
Number of Participants With Any AE, SAE or Death During Part B and Part C
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as ALT \>=3 x ULN, and total bilirubin \>=2 x ULN or international normalized ratio \>1.5.
Time frame: Up to Follow-up (8 weeks)
Population: All Subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A-Placebo | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any AE | 1 Participants |
| Part A-Placebo | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any Death | 0 Participants |
| Part A-Placebo | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any SAE | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any AE | 3 Participants |
| Part A-GSK2890457 | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any Death | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any SAE | 0 Participants |
| Part C-Placebo+Metformin | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any SAE | 0 Participants |
| Part C-Placebo+Metformin | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any AE | 3 Participants |
| Part C-Placebo+Metformin | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any Death | 0 Participants |
| Part C-GSK2890457+Metformin | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any AE | 3 Participants |
| Part C-GSK2890457+Metformin | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any Death | 0 Participants |
| Part C-GSK2890457+Metformin | Number of Participants With Any AE, SAE or Death During Part B and Part C | Any SAE | 0 Participants |
Primary
Number of Participants With Any Hypoglycemic Events During Part A
Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of complete blood count (CBG) or plasma glucose value of \<50 milligram per deciliter (mg/dL) for Part A or \<70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values \<70 mg/dL as a physiological response to altered food intake (e.g., fasting).
Time frame: Up to Follow-up (8 weeks)
Population: All Subjects Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Placebo | Number of Participants With Any Hypoglycemic Events During Part A | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Any Hypoglycemic Events During Part A | 0 Participants |
Primary
Number of Participants With Any Hypoglycemic Events During Part B and Part C
Hypoglycemia is defined as symptoms consistent with hypoglycemia (e.g. dizziness, light-headedness, shakiness) which are confirmed by glucometer measurement of CBG or plasma glucose value of \<50 mg/dL for Part A or \<70 mg/dL for Parts B and C (when possible, CBG values were confirmed with a laboratory measurement). In situations when no glucose sample could be measured at the time of the event, the investigator, at his or her discretion, characterized an event as 'hypoglycemia' based on reported signs and symptoms alone. Healthy participant also had asymptomatic blood glucose values \<70 mg/dL as a physiological response to altered food intake (e.g., fasting).
Time frame: Up to Follow-up (8 weeks)
Population: All Subjects Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A-Placebo | Number of Participants With Any Hypoglycemic Events During Part B and Part C | 0 Participants |
| Part A-GSK2890457 | Number of Participants With Any Hypoglycemic Events During Part B and Part C | 0 Participants |
| Part C-Placebo+Metformin | Number of Participants With Any Hypoglycemic Events During Part B and Part C | 0 Participants |
| Part C-GSK2890457+Metformin | Number of Participants With Any Hypoglycemic Events During Part B and Part C | 0 Participants |
Primary
Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C
During the assessment of body weight in the unit, the participant wore lightweight indoor clothing and removed shoes. The assessments were done pre-dose at Day -1, Day 1, Day 7, Day 14, Day 28, Day 42 and Day 43. Baseline value was defined as the average of Day -1 and Day 1 values. Change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 7, Day 14, Day 28 and Day 42) values. Percent change was calculated by multiplying the change from Baseline value with 100. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to be missing. Day 42 value was the average of Day 42 and Day 43 values.
Time frame: Baseline (Day -1 and Day 1) up to Day 42
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 7 | -0.16 Percent change | Standard Deviation 1.02 |
| Part A-Placebo | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 14 | 0.47 Percent change | Standard Deviation 1.252 |
| Part A-Placebo | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 28 | 0.25 Percent change | Standard Deviation 1.264 |
| Part A-Placebo | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 42 | -0.80 Percent change | Standard Deviation 1.199 |
| Part A-GSK2890457 | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 14 | -0.04 Percent change | Standard Deviation 1.442 |
| Part A-GSK2890457 | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 28 | 0.39 Percent change | Standard Deviation 1.792 |
| Part A-GSK2890457 | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 42 | -0.51 Percent change | Standard Deviation 1.884 |
| Part A-GSK2890457 | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 7 | 0.18 Percent change | Standard Deviation 1.521 |
| Part C-Placebo+Metformin | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 28 | 0.66 Percent change | Standard Deviation 0.813 |
| Part C-Placebo+Metformin | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 14 | 0.79 Percent change | Standard Deviation 1.346 |
| Part C-Placebo+Metformin | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 42 | -0.53 Percent change | Standard Deviation 1.504 |
| Part C-Placebo+Metformin | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 7 | 0.36 Percent change | Standard Deviation 0.719 |
| Part C-GSK2890457+Metformin | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 42 | 0.50 Percent change | Standard Deviation 1.365 |
| Part C-GSK2890457+Metformin | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 14 | 0.60 Percent change | Standard Deviation 0.78 |
| Part C-GSK2890457+Metformin | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 7 | 0.59 Percent change | Standard Deviation 0.892 |
| Part C-GSK2890457+Metformin | Percent Change From Baseline in In-clinic Body Weight During the Double-blind Treatment Period of Part B and C | Day 28 | 0.30 Percent change | Standard Deviation 1.371 |
Comparison: Part B-Placebo+Liraglutide versus Part B-GSK2890457+Liraglutide for Day 42 percent change from Baseline in body weight.95% CI: [-1.64, 1.87]ANCOVA
Comparison: Part C-Placebo+Metformin versus Part C-GSK2890457+Metformin for Day 42 percent change from Baseline in body weight.95% CI: [-0.24, 2.75]ANCOVA
Secondary
Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B
Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post dose. The AUC (0-t) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The analysis population included Liraglutide Pharmacokinetic (PK) Population in Part B comprising of all participants in All Subjects Population for whom a PK sample was obtained and analyzed for Liraglutide.
Time frame: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose
Population: Liraglutide Pharmacokinetic (PK) Population in Part B. Only those participants available at specified time points were analyzed. Results from descriptive summary used Liraglutide PK Population. However, results of statistical analysis compared Day 42 to Day -1 PK in GSK2890457+Liraglutide group who were in the Liraglutide PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 | 2210.15 Hour*nanograms/mL | Geometric Coefficient of Variation 74.9 |
| Part A-Placebo | Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B | Day 42 | 2505.23 Hour*nanograms/mL | Geometric Coefficient of Variation 99.731 |
| Part A-GSK2890457 | Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 | 1268.65 Hour*nanograms/mL | Geometric Coefficient of Variation 91.758 |
| Part A-GSK2890457 | Area Under Plasma Concentration From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Liraglutide During the Double-blind Treatment Period of Part B | Day 42 | 1265.92 Hour*nanograms/mL | Geometric Coefficient of Variation 79.435 |
Comparison: Comparison of Day 42 to Day -1 in GSK2890457+Liraglutide treated participants in the Liraglutide PK Population.90% CI: [0.729, 1.5008]Mixed Models Analysis
Secondary
AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-t]) of Metformin During the Double-blind Treatment Period of Part C
Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The AUC 0-t was planned to be determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.
Time frame: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose
Population: Metformin PK Population in Part C comprised of all participants in the All Subjects Population for whom a PK sample was obtained and analyzed for metformin. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.
Secondary
AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A
Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The AUC (0-10 hour) was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. The analysis population included Metformin PK Population in Part A comprising of all participants in All Subjects Population for whom a PK sample was obtained and analyzed for metformin.
Time frame: Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose
Population: Metformin PK Population in Part A. Only those participants available at specified time points were analyzed. The results from the descriptive summary used the PK Population. However, the results of the statistical analysis compared Day 42 to Day 1 PK only in the GSK2890457 group who were in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A | Day 1 | 4346.8 Hour*nanograms/mL | Geometric Coefficient of Variation 19.1 |
| Part A-Placebo | AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A | Day 42 | 5081.9 Hour*nanograms/mL | Geometric Coefficient of Variation 21.1 |
| Part A-GSK2890457 | AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A | Day 1 | 3402.6 Hour*nanograms/mL | Geometric Coefficient of Variation 26.4 |
| Part A-GSK2890457 | AUC of Metformin From Time 0 to 10 Hours Post-dose (AUC [0-10 Hour]) During the Double-blind Treatment Period of Part A | Day 42 | 2231.7 Hour*nanograms/mL | Geometric Coefficient of Variation 38.6 |
Comparison: Comparison of Day 42 to Day 1 in GSK2890457 treated participants in the PK Population.90% CI: [0.585, 0.779]Mixed Models Analysis
Secondary
Cmax of Metformin During the Double-blind Treatment Period of Part A
Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The first occurrence of the Cmax was determined directly from the raw concentration-time data.
Time frame: Day 1 and Day 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose
Population: Metformin PK Population in Part A. Only those participants available at specified time points were analyzed. The results from the descriptive summary used the PK Population. However, the results of the statistical analysis compared Day 42 to Day 1 PK only in the GSK2890457 group who were in the PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Cmax of Metformin During the Double-blind Treatment Period of Part A | Day 1 | 681.8 Nanograms/mL | Geometric Coefficient of Variation 19 |
| Part A-Placebo | Cmax of Metformin During the Double-blind Treatment Period of Part A | Day 42 | 860.1 Nanograms/mL | Geometric Coefficient of Variation 18.8 |
| Part A-GSK2890457 | Cmax of Metformin During the Double-blind Treatment Period of Part A | Day 1 | 576.2 Nanograms/mL | Geometric Coefficient of Variation 24.4 |
| Part A-GSK2890457 | Cmax of Metformin During the Double-blind Treatment Period of Part A | Day 42 | 374.1 Nanograms/mL | Geometric Coefficient of Variation 31.2 |
Comparison: Comparison of Day 42 to Day 1 in GSK2890457 treated participants in the PK Population.90% CI: [0.578, 0.757]Mixed Models Analysis
Secondary
Cmax of Metformin During the Double-blind Treatment Period of Part C
Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The first occurrence of the Cmax was planned to be determined directly from the raw concentration-time data. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.
Time frame: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose
Population: Metformin PK Population in Part C. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.
Secondary
Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B
Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The first occurrence of the Cmax was determined directly from the raw concentration-time data.
Time frame: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose
Population: Liraglutide PK Population in Part B. Only those participants available at the specified time points were analyzed. Results from descriptive summary used Liraglutide PK Population. However, results of statistical analysis compared Day 42 to Day -1 PK in GSK2890457+Liraglutide group who were in the Liraglutide PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A-Placebo | Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 | 120.00 Nanograms/mL | Geometric Coefficient of Variation 66.845 |
| Part A-Placebo | Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day 42 | 128.57 Nanograms/mL | Geometric Coefficient of Variation 86.86 |
| Part A-GSK2890457 | Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 | 72.24 Nanograms/mL | Geometric Coefficient of Variation 70.492 |
| Part A-GSK2890457 | Maximum Observed Concentration (Cmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day 42 | 70.86 Nanograms/mL | Geometric Coefficient of Variation 63.525 |
Comparison: Comparison of Day 42 to Day -1 in GSK2890457+Liraglutide treated participants in the Liraglutide PK Population.90% CI: [0.781, 1.3673]Mixed Models Analysis
Secondary
Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B
Blood samples were collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The time at which Cmax was observed was determined directly from the raw concentration-time data.
Time frame: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8, 10, 11.5, 12, 14 and 24 hours post-dose
Population: Liraglutide PK Population in Part B. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A-Placebo | Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 | 9.74 Hours |
| Part A-Placebo | Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day 42 | 9.92 Hours |
| Part A-GSK2890457 | Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day 42 | 9.98 Hours |
| Part A-GSK2890457 | Time of Occurrence of Cmax (Tmax) of Liraglutide During the Double-blind Treatment Period of Part B | Day -1 | 8.00 Hours |
Secondary
Tmax of Metformin During the Double-blind Treatment Period of Part A
Blood samples were collected on Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8 and 10 (pre-dinner) hours post-dose. The time at which Cmax was observed was determined directly from the raw concentration-time data.
Time frame: Day 1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4, 5.5, 6, 8 and 10 hours post-dose
Population: Metformin PK Population in Part A. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A-Placebo | Tmax of Metformin During the Double-blind Treatment Period of Part A | Day 1 | 3.010 Hours |
| Part A-Placebo | Tmax of Metformin During the Double-blind Treatment Period of Part A | Day 42 | 4.000 Hours |
| Part A-GSK2890457 | Tmax of Metformin During the Double-blind Treatment Period of Part A | Day 1 | 2.000 Hours |
| Part A-GSK2890457 | Tmax of Metformin During the Double-blind Treatment Period of Part A | Day 42 | 2.000 Hours |
Secondary
Tmax of Metformin During the Double-blind Treatment Period of Part C
Blood samples were planned to be collected on Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose. The time at which Cmax was observed was planned to be determined directly from the raw concentration-time data. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.
Time frame: Day -1 and 42 at pre-dose (0 hour), 15 minutes, 30 minutes, 1, 1.5, 2, 4 (pre-lunch), 5.5, 6, 8, 10 (pre-dinner), 11.5, 12, 14 and 24 hours post-dose
Population: Metformin PK Population in Part C. The data for PK parameters of metformin during Part C was not collected due to variations in formulation and regimen.