Diabetes Mellitus, Type 2
Conditions
Keywords
Pharmacokinetics, Glucose, Safety, Male, Female, Metformin, Pharmacodynamics, Tolerability, Type II Diabetes
Brief summary
A study in type 2 diabetic subjects on stable metformin therapy to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of co-administering single and multiple oral doses of GSK1292263
Detailed description
This study will investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of GSK1292263 when co-administered with metformin. The study will be in 2 parts. Part A will determine the PK of GSK1292263 following single day dosing of type 2 diabetes (T2DM) subjects on metformin. Part B will investigate the effects of 14d of co-dosing of GSK1292263 BID, 50mg BID of sitagliptin or placebo to 48 T2DM subjects taking metformin.
Interventions
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects, 18 - 65 years of age, inclusive. * Females of non-childbearing potential. * Male subjects willing to employ appropriate contraception. * Except as noted elsewhere, subjects should have no significant known medical conditions other than T2DM that would affect the safety of the subject or the objectives of the study. * BMI (body mass index) within the range 21.8-37.5 kg/m2. * T2DM diagnosed by American Diabetes Association criteria for at least 3 month prior to screening. * Currently on stable metformin therapy. * Fasting plasma glucose \<= 250mg/dL. * HbA1c between 6.5 and 11.0%. * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. * Average QTcB or QTcF \< 450 msec; or QTc \< 480 msec in subjects with right bundle branch block. Subjects with left bundle branch block are not eligible. * AST and ALT \< 2xULN; alkaline phosphatase and bilirubin \<=1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%). Subjects with Gilbert's syndrome are allowed to participate in the study.
Exclusion criteria
* Positive for Hepatitis B or C, or HIV. * History of uncorrected thyroid dysfunction or an abnormal thyroid function test. * History of ketoacidosis or lactic acidosis. * Fasting triglycerides \> 450mg/dL. * For females a hemoglobin \< 11.5g/dL, and for males a hemoglobin \< 12.5g/dL. * Positive drug/alcohol screen. * Smoking. * If female is pregnant or has a positive pregnancy test or is lactating. * Significant renal disease. * Significant ECG abnormalities. * Systolic blood pressure \> 150mmHg or \<80mmHg or diastolic blood pressure \> 95mmHg or \<60mmHg at screening. * Previous use of insulin as a treatment within 3 months of screening, or for \>2 weeks when used for acute illness in the last 12 months prior to screening, or if used for more than 1 year when associated with gestational diabetes mellitus. * History of: clinically significant symptoms of gastroparesis; symptomatic cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to screening; gastrointestinal disease that could affect fat or bile acid absorption, or the pharmacokinetics or pharmacodynamics of the study drugs, including inflammatory bowel disease, chronic diarrhea, Crohn's or malabsorption syndromes within the past year; gastrointestinal surgery that may affect the pharmacokinetics or pharmacodynamics of the study drugs; or, chronic or acute pancreatitis. * History of regular alcohol consumption within 6 months. * Urinary cotinine levels indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 6 months. * Has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication. * Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * Is taking prohibited medications. In Parts A and B, subjects will not be allowed to wash-off of unapproved anti-diabetic medications in order to qualify for participation in this study. • Subjects must wash out from the following medications during the 7-day period prior to first dose, and must remain off these medications through discharge on Day 2 (Part A) or Day 15 (Part B): all statin agents, fat absorption blocking agents, bile acid sequestrants. Fibrates must be washed out for a 14-day period prior to first dose. • Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study medication. * Unwilling to abstain from: Caffeine-or xanthine-containing products from Day -7 until D2 (Part A) or Day -7 through Day 15 (Part B); use of illicit drugs or nicotine-containing products; alcohol from Day -7 prior to dosing until D2 (Part A) or Day -7 through Day 15 (Part B); Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until collection of the final pharmacokinetic blood samples. * History of sensitivity to any of the study medications, or components thereof, or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. This includes sensitivity to heparin or heparin-induced thrombocytopenia, if heparin will be used to maintain catheter patency. * Where participation in the study would result in donation of blood in excess of approximately 500mL within a 56 day period. * Subject is either an immediate family member of a participating investigator, study coordinator, employee of an investigator; or is a member of the staff conducting the study. * Unwillingness or inability to follow the procedures outlined in the protocol. * Subject is mentally or legally incapacitated.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (Part A) | Up to 10 days after discharge (Day 2) in Part A | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. |
| Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Up to 10 days after discharge (Day 15) in Part B | An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. |
| Number of Participants With Abnormal Hematology Values of Potential Clinical Importance (PCI) (Part A) | Up to 10 days after discharge (Day 2) in Part A | Blood samples for hematology assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Hematology parameter: Total Neutrophil count was assessed for abnormal value of PCI. The range of PCI value was: \<0.83 x lower limit normal (LLN) with unit x10\^9 per liter |
| Number of Participants With Abnormal Hematology Values of PCI (Part B) | Up to 10 days after discharge (Day 15) in Part B | Blood samples for hematology assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Hematology parameters: Hematocrit (unit: ratio) and hemoglobin (unit: grams per liter \[g/L\]), were assessed for abnormal values of PCI. The PCI range for hematocrit was: \>0.075 decrease from Baseline (low), \>1.02 x upper limit normal (ULN) (high-male), \>1.17 x ULN (high-female). The PCI range for hemoglobin was: \>25 decrease from Baseline (low), \>1.03 x ULN (high-male), \>1.13 x ULN (high-female). Data has been presented for the number of participants with hematology data values high from the PCI range in a consolidated format. |
| Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part A) | Up to 10 days after discharge (Day 2) in Part A | Blood samples for chemistry assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Clinical chemistry parameter: Glucose (unit: millimoles per liter \[mmol/L\]) was assessed for abnormal high value of PCI. The normal range was 3.6 to 5.5 mmol/L |
| Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Up to 10 days after discharge (Day 15) in Part B | Blood samples for chemistry assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Clinical chemistry parameters: Aspartate amino transferase (unit: international unit per liter \[IU/L\]) and Total bilirubin (unit: micromoles per liter (µmol/L) were assessed for abnormal values of PCI. For aspartate aminotransferase the PCI range was \>=2 x ULN (high). For total bilirubin the PCI range was \>=1.5 x ULN (high). |
| Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Up to 10 days after discharge (Day 2) in Part A | Urinalysis parameters: Urine occult blood, Urine Glucose, Urine ketones and Urine protein were assessed for abnormal findings by dipstick analysis. The abnormalities were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome. |
| Number of Participants With Abnormal Urinalysis Data Values (Part B) | Up to 10 days after discharge (Day 15) in Part B | Urinalysis parameters: Urine occult blood, Urine glucose, Urine ketones, Urine protein, White blood cells were assessed for abnormal findings by dipstick analysis. The abnormal findings were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome. |
| Mean Value of Urine Albumin at Follow up (Part A) | Up to 10 days after discharge (Day 2) in Part A | Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urine albumin was assessed using quantitative analysis. |
| Mean Value of Urine Albumin (Part B) | Up to 10 days after discharge (Day 15) in Part B | Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urine albumin was assessed using quantitative analysis. |
| Mean Value of Urine pH (Part A) | Up to 10 days after discharge (Day 2) in Part A | Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is 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. |
| Mean Value of Urine pH (Part B) | Up to 10 days after discharge (Day 15) in Part B | Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is 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. |
| Mean Value of Urine Specific Gravity (Part A) | Up to 10 days after discharge (Day 2) in Part A | Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine . |
| Mean Value of Urine Specific Gravity (Part B) | Up to 10 days after discharge (Day 15) in Part B | Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine . |
| Number of Participants With Abnormal Vital Signs of PCI (Part A) | Up to 10 days after discharge (Day 2) in Part A | Assessment of vital signs (including systolic, diastolic blood pressure and heart rate) was performed at one time point at Screening, at follow-up and pre-breakfast on Day -1. On Day 1, they were taken at pre-breakfast, 1 hour, 3, 4, 6, 10, 16 and 24 hours post-dose. Assessments were made in triplicate at the pre-breakfast time point, and single assessments were made at all other times. Assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. PCI value of systolic blood pressure: \<85 and \>160 millimeter of mercury (mmHg). PCI value of diastolic blood pressure: \<45 and \>100 mmHg. PCI value of heart rate: \<40 and \>110 beats per minute. |
| Number of Participants With Abnormal Vital Signs of PCI (Part B) | Up to 10 days after discharge (Day 15) in Part B | Assessment of vital signs (including systolic and diastolic blood pressure and heart rate) was performed at Screening, pre-breakfast on Days -1 to 14 in a fasting state early in the morning (prior to morning dosing on Days 1-14), and at Follow-up. On Days 1, 7 and 14, they were taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Up to 10 days after discharge (Day 2) in Part A | ECGs were taken at Screening, pre-breakfast on Day -1, on Day 1 (pre-breakfast, 1 hour, 2, 3, 4, 6, 8, 13, 24hours post-dose), and at follow-up. Assessments were made in triplicate on Day 1 at the pre-breakfast time point, and single assessments were made at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS). |
| Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Up to 10 days after discharge (Day 15) in Part B | ECGs were taken at Screening, pre-breakfast on Day -1 and at Follow-up. On Days 1, 7 and 14 ECGs were taken pre-breakfast (fasting) and at 1, 2, 4, 6, 8, 12 and 24hours post-dose. Triplicate ECGs were taken at the pre-breakfast time point, and single assessments were taken at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS). |
| Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours [AUC (0-24)] and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-last)] Following a Single Dose of GSK1292263 (Part A) | On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. | Blood samples for the determination of pharmacokinetics (PK) were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-last) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. |
| Maximum Observed Concentration (Cmax) Following a Single Dose of GSK1292263 (Part A) | On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. | Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data. |
| Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) and Time of Occurrence of Cmax (Tmax) Following a Single Dose of GSK1292263 (Part A) | On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. | Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only. |
| Apparent Clearance Following Oral Dosing (CL/F) of GSK1292263 (Part A) | On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. | Outcome measure was added with caveat as data permits. The data for CL/F was not collected. |
| Volume of Distribution (V/F) (Part A) | On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. | Outcome measure was added with caveat as data permits. The data for V/F was not collected. |
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) Following a Single Dose of GSK1292263 (Part A) | On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. | Outcome measure was added with caveat as data permits. The data for AUC (0-inf) was not collected. |
| Terminal Phase Half-life (t1/2) Following a Single Dose of GSK1292263 (Part A) | On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. | Outcome measure was added with caveat as data permits. The data for t1/2 was not collected. |
| Cmax Following Repeat Dose of GSK1292263 (Part B) | On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). | Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data. |
| Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). | Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only. |
| AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). | Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-10) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. |
| T1/2 Following Repeat Dose of GSK1292263 (Part B) | On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). | Outcome measure was added with caveat as data permits. The data for T1/2 was not collected. |
| Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. | Accumulation ratio (Ro) was derived as: Ro = Day 14 morning AUC(0-10)/Day 1 morning AUC(0-10) (for BID regimens only). Ro = Day 14 AUC(0-24)/Day 1 AUC(0-24) (for both BID and once daily regimens). Accumulation ratio (RCmax)= Day 14 Cmax/Day 1 Cmax. RCmax was not computed for each dosing period (morning and evening). |
| Change From Baseline in Mean Fasted Glucose Value (Part A) | Baseline and at pre-breakfast on Day 1 and 24 h post-dose. | Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. |
| Change From Baseline in Mean Fasted Insulin Value (Part A) | Baseline and at pre-breakfast on Day 1 and 24 hours post-dose. | Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. |
| Change From Baseline in Mean Fasted Glucose Value (Part B) | Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose. | Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. |
| Change From Baseline in Mean Fasted Insulin Value (Part B) | Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose. | Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. |
| Mean Post Meal Glucose Value (Part B) | At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose. | Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner. |
| Mean Post Meal Insulin Value (Part B) | At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose. | Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner. |
| Change From Baseline in Weighted Mean for Glucose Value (Part B) | Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose. | Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. Weighted mean were assessed for (0-12) and (0-24). AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing. |
| Change From Baseline in Weighted Mean for Insulin Value (Part B) | Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose. | Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing. |
| Number of Participants With Relationship Between GSK1292263 Drug Exposures and Pharmacodynamic Parameters (Part B) | At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose | Data was not collected for this outcome measure. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at two study centers in the United States from 23 November 2009 up to 12 April 2010. The study consisted of open label Part A and single-blind Part B. Total 6 participants were randomized in Part A whereas total 67 participants were randomized in Part B.
Participants by arm
| Arm | Count |
|---|---|
| Part A: GSK1292263 300 mg Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day). | 6 |
| Part B: GSK1292263 75 mg/300 mg/ 600 mg Participants received one of three dosing regimens of GSK1292263: 75 mg twice daily (BID) (as 1 x 75 mg tablet GSK1292263 + 2 placebo tablets in morning and evening), 300 mg BID (as 1 x 200 mg tablet + 1 x 75 mg tablet + 1 x 25 mg tablet GSK1292263 in morning and evening) and 600 mg once daily (QD) (as 3 x 200 mg tablets GSK1292263 in morning + 3 x placebo tablets in evening) or matching placebo BID (as 3 x placebo tablets in morning and evening), or open-label sitagliptin 50 mg BID for 14 days. Seven days before enrollment in Part B, participants taking metformin three times daily (TID) or using an extended-release formulation were converted to the equivalent total daily dose of immediate release metformin administered BID. | 67 |
| Total | 73 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Part B: GSK1292263 75 mg/300 mg/ 600 mg | Reached defined stopping criteria | 0 | 2 |
Baseline characteristics
| Characteristic | Part B: GSK1292263 75 mg/300 mg/ 600 mg | Total | Part A: GSK1292263 300 mg |
|---|---|---|---|
| Age, Customized 36 to 65 Years | 67 Participants | 73 Participants | 6 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 8 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 61 Participants | 65 Participants | 4 Participants |
| Sex: Female, Male Female | 28 Participants | 29 Participants | 1 Participants |
| Sex: Female, Male Male | 39 Participants | 44 Participants | 5 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 / 6 | 0 / 14 | 0 / 13 | 0 / 12 | 0 / 15 | 0 / 13 |
| other Total, other adverse events | 0 / 6 | 2 / 14 | 3 / 13 | 3 / 12 | 4 / 15 | 5 / 13 |
| serious Total, serious adverse events | 0 / 6 | 0 / 14 | 0 / 13 | 0 / 12 | 0 / 15 | 0 / 13 |
Outcome results
Primary
Apparent Clearance Following Oral Dosing (CL/F) of GSK1292263 (Part A)
Outcome measure was added with caveat as data permits. The data for CL/F was not collected.
Time frame: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Primary
Area Under the Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC [0-inf]) Following a Single Dose of GSK1292263 (Part A)
Outcome measure was added with caveat as data permits. The data for AUC (0-inf) was not collected.
Time frame: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Population: PK Population
Primary
Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours [AUC (0-24)] and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-last)] Following a Single Dose of GSK1292263 (Part A)
Blood samples for the determination of pharmacokinetics (PK) were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-last) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time frame: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Population: The PK Population included participants from the Safety Population who had any PK parameter estimated. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours [AUC (0-24)] and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-last)] Following a Single Dose of GSK1292263 (Part A) | AUC (0-last) | 10099.35 nanograms hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 14.332 |
| Part A | Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours [AUC (0-24)] and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-last)] Following a Single Dose of GSK1292263 (Part A) | AUC (0-24) | 7046.25 nanograms hour per milliliter (ng*hr/mL) | Geometric Coefficient of Variation 11.09 |
Primary
AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B)
Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-10) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.
Time frame: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 7 | 2930.47 ng*hr/mL | Geometric Coefficient of Variation 21.366 |
| Part A | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-24), Day 14 | 7785.24 ng*hr/mL | Geometric Coefficient of Variation 19.152 |
| Part A | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-24), Day 1 | 3775.76 ng*hr/mL | Geometric Coefficient of Variation 30.915 |
| Part A | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 14 | 3130.50 ng*hr/mL | Geometric Coefficient of Variation 22.43 |
| Part A | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 1 | 1143.35 ng*hr/mL | Geometric Coefficient of Variation 36.439 |
| GSK1292263 75 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 14 | 6057.41 ng*hr/mL | Geometric Coefficient of Variation 32.784 |
| GSK1292263 75 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-24), Day 14 | 15479.48 ng*hr/mL | Geometric Coefficient of Variation 33.009 |
| GSK1292263 75 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 7 | 6472.68 ng*hr/mL | Geometric Coefficient of Variation 29.79 |
| GSK1292263 75 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-24), Day 1 | 9968.88 ng*hr/mL | Geometric Coefficient of Variation 39.959 |
| GSK1292263 75 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 1 | 3149.94 ng*hr/mL | Geometric Coefficient of Variation 38.937 |
| GSK1292263 300 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-24), Day 14 | 9391.30 ng*hr/mL | Geometric Coefficient of Variation 32.948 |
| GSK1292263 300 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 1 | NA ng*hr/mL | — |
| GSK1292263 300 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-24), Day 1 | 6791.90 ng*hr/mL | Geometric Coefficient of Variation 24.55 |
| GSK1292263 300 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 7 | 5205.86 ng*hr/mL | Geometric Coefficient of Variation 31.529 |
| GSK1292263 300 mg | AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) | AUC (0-10), Day 14 | NA ng*hr/mL | — |
Primary
Change From Baseline in Mean Fasted Glucose Value (Part A)
Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.
Time frame: Baseline and at pre-breakfast on Day 1 and 24 h post-dose.
Population: The Pharmacodynamic (PD) Population included participants from the Safety Population who had any PD parameter estimated. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A | Change From Baseline in Mean Fasted Glucose Value (Part A) | 0.17 millimoles per liter (mmol/L) | Geometric Coefficient of Variation -199.736 |
Primary
Change From Baseline in Mean Fasted Glucose Value (Part B)
Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.
Time frame: Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Population: PD Population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 7, pre-breakfast | -0.53 mmol/L |
| Part A | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, 24 hours | -0.01 mmol/L |
| Part A | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, pre-breakfast | -0.74 mmol/L |
| GSK1292263 75 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, pre-breakfast | -1.57 mmol/L |
| GSK1292263 75 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, 24 hours | -0.57 mmol/L |
| GSK1292263 75 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 7, pre-breakfast | -0.74 mmol/L |
| GSK1292263 300 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, pre-breakfast | -0.81 mmol/L |
| GSK1292263 300 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 7, pre-breakfast | -0.28 mmol/L |
| GSK1292263 300 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, 24 hours | 0.66 mmol/L |
| GSK1292263 600 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 7, pre-breakfast | 0.21 mmol/L |
| GSK1292263 600 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, 24 hours | 0.68 mmol/L |
| GSK1292263 600 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, pre-breakfast | -0.11 mmol/L |
| Sitagliptin 50 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, pre-breakfast | -1.83 mmol/L |
| Sitagliptin 50 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 7, pre-breakfast | -1.75 mmol/L |
| Sitagliptin 50 mg | Change From Baseline in Mean Fasted Glucose Value (Part B) | Day 14, 24 hours | -1.06 mmol/L |
Comparison: Placebo vs GSK1292263 75 mg: Day 7, pre-breakfast95% CI: [-1, 0.57]
Comparison: Placebo vs GSK1292263 300 mg: Day 7, pre-breakfast95% CI: [-0.53, 1.11]
Comparison: Placebo vs GSK1292263 600 mg: Day 7, pre-breakfast95% CI: [-0.02, 1.52]
Comparison: Placebo vs Sitagliptin 50 mg: Day 7, pre-breakfast95% CI: [-2.01, -0.41]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Day 7 , pre-breakfast95% CI: [0.18, 1.81]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast95% CI: [0.66, 2.34]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast95% CI: [1.16, 2.75]
Comparison: Placebo vs GSK1292263 75 mg: Day 14, pre-breakfast95% CI: [-1.74, 0.18]
Comparison: Placebo vs GSK1292263 300 mg: Day 14, pre-breakfast95% CI: [-0.81, 1.19]
Comparison: Placebo vs GSK1292263 600 mg: Day 14, pre-breakfast95% CI: [-0.35, 1.55]
Comparison: Placebo vs Sitagliptin 50 mg: Day 14, pre-breakfast95% CI: [-2.05, -0.08]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast95% CI: [-0.71, 1.29]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast95% CI: [0.22, 2.29]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast95% CI: [0.68, 2.65]
Comparison: Placebo vs GSK1292263 75 mg: Day 14, 24 hours95% CI: [-1.65, 0.54]
Comparison: Placebo vs GSK1292263 300 mg: Day 14, 24 hours95% CI: [-0.4, 1.89]
Comparison: Placebo vs GSK1292263 600 mg: Day 14, 24 hours95% CI: [-0.36, 1.78]
Comparison: Placebo vs Sitagliptin 50 mg: Day 14, 24 hours95% CI: [-2.15, 0.09]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Day 14, 24 hours95% CI: [-0.66, 1.61]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Day 14, 24 hours95% CI: [0.6, 2.95]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Day 14, 24 hours95% CI: [0.63, 2.86]
Primary
Change From Baseline in Mean Fasted Insulin Value (Part A)
Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.
Time frame: Baseline and at pre-breakfast on Day 1 and 24 hours post-dose.
Population: PD Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A | Change From Baseline in Mean Fasted Insulin Value (Part A) | 3.45 picomoles per liter (pmol/L) | Geometric Coefficient of Variation -187.128 |
Primary
Change From Baseline in Mean Fasted Insulin Value (Part B)
Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.
Time frame: Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Population: PD Population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, pre-breakfast | 4.84 pmol/L |
| Part A | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, 24 hours | 23.25 pmol/L |
| Part A | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 7, pre-breakfast | -2.74 pmol/L |
| GSK1292263 75 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, 24 hours | 4.97 pmol/L |
| GSK1292263 75 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, pre-breakfast | 6.22 pmol/L |
| GSK1292263 75 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 7, pre-breakfast | -1.84 pmol/L |
| GSK1292263 300 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 7, pre-breakfast | -26.34 pmol/L |
| GSK1292263 300 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, 24 hours | -12.54 pmol/L |
| GSK1292263 300 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, pre-breakfast | -13.48 pmol/L |
| GSK1292263 600 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, pre-breakfast | -33.26 pmol/L |
| GSK1292263 600 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 7, pre-breakfast | -22.99 pmol/L |
| GSK1292263 600 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, 24 hours | -17.52 pmol/L |
| Sitagliptin 50 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, 24 hours | 27.47 pmol/L |
| Sitagliptin 50 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 14, pre-breakfast | 4.43 pmol/L |
| Sitagliptin 50 mg | Change From Baseline in Mean Fasted Insulin Value (Part B) | Day 7, pre-breakfast | 2.07 pmol/L |
Comparison: Placebo vs GSK1292263 75 mg: Day 7, pre-breakfast95% CI: [-17.17, 17.56]
Comparison: Placebo vs GSK1292263 300 mg: Day 7, pre-breakfast95% CI: [-34.7, 0.98]
Comparison: Placebo vs GSK1292263 600 mg: Day 7, pre-breakfast95% CI: [-23.04, 12.12]
Comparison: Placebo vs Sitagliptin 50 mg: Day 7, pre-breakfast95% CI: [-13.89, 21.58]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast95% CI: [-21.7, 14.39]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast95% CI: [-39.25, -2.17]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Day 7, pre-breakfast95% CI: [-27.63, 9.01]
Comparison: Placebo vs GSK1292263 75 mg: Day 14, pre-breakfast95% CI: [-19.43, 12.14]
Comparison: Placebo vs GSK1292263 300 mg: Day 14, pre-breakfast95% CI: [-32.72, -0.6]
Comparison: Placebo vs GSK1292263 600 mg: Day 14, pre-breakfast95% CI: [-38.34, -6.16]
Comparison: Placebo vs Sitagliptin 50 mg: Day 14, pre-breakfast95% CI: [-20.69, 11.51]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast95% CI: [-15.4, 17.28]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast95% CI: [-28.82, 4.68]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Day 14, pre-breakfast95% CI: [-34.72, -0.6]
Comparison: Placebo vs GSK1292263 75 mg: Day 14, 24 hours95% CI: [-44, 5.8]
Comparison: Placebo vs GSK1292263 300 mg: Day 14, 24 hours95% CI: [-53.56, -2.39]
Comparison: Placebo vs GSK1292263 600 mg: Day 14, 24 hours95% CI: [-48.82, 1.6]
Comparison: Placebo vs Sitagliptin 50 mg: Day 14, 24 hours95% CI: [-22.34, 28.53]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Day 14, 24 hours95% CI: [-48.07, 3.69]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Day 14, 24 hours95% CI: [-57.66, -4.48]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Day 14, 24 hours95% CI: [-52.98, -0.42]
Primary
Change From Baseline in Weighted Mean for Glucose Value (Part B)
Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. Weighted mean were assessed for (0-12) and (0-24). AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing.
Time frame: Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Population: PD Population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-24), Day 14 | -0.414 mmol/L |
| Part A | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 14 | -0.235 mmol/L |
| Part A | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 7 | 0.064 mmol/L |
| GSK1292263 75 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 14 | -0.539 mmol/L |
| GSK1292263 75 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-24), Day 14 | -0.555 mmol/L |
| GSK1292263 75 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 7 | -0.432 mmol/L |
| GSK1292263 300 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-24), Day 14 | 0.321 mmol/L |
| GSK1292263 300 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 14 | 0.123 mmol/L |
| GSK1292263 300 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 7 | 0.555 mmol/L |
| GSK1292263 600 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 14 | 0.656 mmol/L |
| GSK1292263 600 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-24), Day 14 | 0.837 mmol/L |
| GSK1292263 600 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 7 | 1.103 mmol/L |
| Sitagliptin 50 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 7 | -0.862 mmol/L |
| Sitagliptin 50 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-12), Day 14 | -1.039 mmol/L |
| Sitagliptin 50 mg | Change From Baseline in Weighted Mean for Glucose Value (Part B) | Weighted mean (0-24), Day 14 | -1.025 mmol/L |
Comparison: Placebo vs GSK1292263 75 mg: Weighted Mean (0-12), Day 795% CI: [-1.5, 0.5]
Comparison: Placebo vs GSK1292263 300 mg: Weighted Mean (0-12), Day 795% CI: [-0.51, 1.54]
Comparison: Placebo vs GSK1292263 600 mg: Weighted Mean (0-12), Day 795% CI: [0.05, 2.01]
Comparison: Placebo vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 795% CI: [-1.98, 0.07]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 795% CI: [-0.59, 1.5]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 795% CI: [0.39, 2.55]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 795% CI: [0.96, 3.01]
Comparison: Placebo vs GSK1292263 75 mg: Weighted Mean (0-12), Day 1495% CI: [-1.38, 0.76]
Comparison: Placebo vs GSK1292263 300 mg: Weighted Mean (0-12), Day 1495% CI: [-0.7, 1.49]
Comparison: Placebo vs GSK1292263 600 mg: Weighted Mean (0-12), Day 1495% CI: [-0.18, 1.93]
Comparison: Placebo vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 1495% CI: [-1.95, 0.25]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 1495% CI: [-0.58, 1.66]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 1495% CI: [0.09, 2.4]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 1495% CI: [0.63, 2.83]
Comparison: Placebo vs GSK1292263 75 mg: Weighted Mean (0-24), Day 1495% CI: [-1.21, 0.91]
Comparison: Placebo vs GSK1292263 300 mg: Weighted Mean (0-24), Day 1495% CI: [-0.34, 1.81]
Comparison: Placebo vs GSK1292263 600 mg: Weighted Mean (0-24), Day 1495% CI: [0.21, 2.28]
Comparison: Placebo vs Sitagliptin 50 mg: Weighted Mean (0-24), Day 1495% CI: [-1.71, 0.46]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Weighted Mean (0-24), Day 1495% CI: [-0.62, 1.57]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Weighted Mean (0-24), Day 1495% CI: [0.23, 2.49]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Weighted Mean (0-24), Day 1495% CI: [0.79, 2.95]
Primary
Change From Baseline in Weighted Mean for Insulin Value (Part B)
Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing.
Time frame: Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Population: PD Population
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 14 | 21.751 pmol/L |
| Part A | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-24), Day 14 | 22.127 pmol/L |
| Part A | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 7 | 6.146 pmol/L |
| GSK1292263 75 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 14 | 6.672 pmol/L |
| GSK1292263 75 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-24), Day 14 | 4.626 pmol/L |
| GSK1292263 75 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 7 | -19.241 pmol/L |
| GSK1292263 300 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 7 | -47.290 pmol/L |
| GSK1292263 300 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-24), Day 14 | -35.220 pmol/L |
| GSK1292263 300 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 14 | -42.657 pmol/L |
| GSK1292263 600 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 7 | -36.334 pmol/L |
| GSK1292263 600 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-24), Day 14 | -31.067 pmol/L |
| GSK1292263 600 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 14 | -33.753 pmol/L |
| Sitagliptin 50 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 14 | 17.328 pmol/L |
| Sitagliptin 50 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-24), Day 14 | 18.848 pmol/L |
| Sitagliptin 50 mg | Change From Baseline in Weighted Mean for Insulin Value (Part B) | Weighted mean (0-12), Day 7 | 5.979 pmol/L |
Comparison: Placebo vs GSK1292263 75 mg: Weighted Mean (0-12), Day 795% CI: [-59.25, 2.01]
Comparison: Placebo vs GSK1292263 300 mg: Weighted Mean (0-12), Day 795% CI: [-79.23, -16.56]
Comparison: Placebo vs GSK1292263 600 mg: Weighted Mean (0-12), Day 795% CI: [-55.53, 6.2]
Comparison: Placebo vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 795% CI: [-36.76, 25.89]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 795% CI: [-55, 8.63]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 795% CI: [-75.18, -9.74]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 795% CI: [-51.83, 13.37]
Comparison: Placebo vs GSK1292263 75 mg: Weighted Mean (0-12), Day 1495% CI: [-49.15, 12.28]
Comparison: Placebo vs GSK1292263 300 mg: Weighted Mean (0-12), Day 1495% CI: [-90.08, -27.24]
Comparison: Placebo vs GSK1292263 600 mg: Weighted Mean (0-12), Day 1495% CI: [-67.96, -6.05]
Comparison: Placebo vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 1495% CI: [-41.31, 21.52]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 1495% CI: [-40.44, 23.36]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 1495% CI: [-81.58, -15.95]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Weighted Mean (0-12), Day 1495% CI: [-59.8, 5.58]
Comparison: Placebo vs GSK1292263 75 mg: Weighted Mean (0-24), Day 1495% CI: [-48.95, 8.23]
Comparison: Placebo vs GSK1292263 300 mg: Weighted Mean (0-24), Day 1495% CI: [-82.92, -24.5]
Comparison: Placebo vs GSK1292263 600 mg: Weighted Mean (0-24), Day 1495% CI: [-66.24, -8.86]
Comparison: Placebo vs Sitagliptin 50 mg: Weighted Mean (0-24), Day 1495% CI: [-37.2, 21.27]
Comparison: GSK1292263 75 mg vs Sitagliptin 50 mg: Weighted Mean (0-24), Day 1495% CI: [-42.1, 17.3]
Comparison: GSK1292263 300 mg vs Sitagliptin 50 mg: Weighted Mean (0-24), Day 1495% CI: [-76.2, -15.3]
Comparison: GSK1292263 600 mg vs Sitagliptin 50 mg: Weighted Mean (0-24), Day 1495% CI: [-59.82, 0.64]
Primary
Cmax Following Repeat Dose of GSK1292263 (Part B)
Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data.
Time frame: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 7 | 416.441 ng/mL | Geometric Coefficient of Variation 30.0099 |
| Part A | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 1 | 278.451 ng/mL | Geometric Coefficient of Variation 36.5951 |
| Part A | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 14 | 457.716 ng/mL | Geometric Coefficient of Variation 20.4386 |
| GSK1292263 75 mg | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 14 | 902.325 ng/mL | Geometric Coefficient of Variation 30.0011 |
| GSK1292263 75 mg | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 1 | 686.845 ng/mL | Geometric Coefficient of Variation 33.1747 |
| GSK1292263 75 mg | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 7 | 872.843 ng/mL | Geometric Coefficient of Variation 22.2509 |
| GSK1292263 300 mg | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 7 | 738.918 ng/mL | Geometric Coefficient of Variation 39.1209 |
| GSK1292263 300 mg | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 14 | 664.505 ng/mL | Geometric Coefficient of Variation 37.8497 |
| GSK1292263 300 mg | Cmax Following Repeat Dose of GSK1292263 (Part B) | Day 1 | 610.586 ng/mL | Geometric Coefficient of Variation 29.2427 |
Primary
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) and Time of Occurrence of Cmax (Tmax) Following a Single Dose of GSK1292263 (Part A)
Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only.
Time frame: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Population: PK Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) and Time of Occurrence of Cmax (Tmax) Following a Single Dose of GSK1292263 (Part A) | Tmax | 5.00 hour |
| Part A | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) and Time of Occurrence of Cmax (Tmax) Following a Single Dose of GSK1292263 (Part A) | Tlag | 0.000 hour |
Primary
Maximum Observed Concentration (Cmax) Following a Single Dose of GSK1292263 (Part A)
Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data.
Time frame: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Population: PK Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A | Maximum Observed Concentration (Cmax) Following a Single Dose of GSK1292263 (Part A) | 582.619 nanograms per milliliter (ng/mL) | Geometric Coefficient of Variation 28.071 |
Primary
Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B)
Accumulation ratio (Ro) was derived as: Ro = Day 14 morning AUC(0-10)/Day 1 morning AUC(0-10) (for BID regimens only). Ro = Day 14 AUC(0-24)/Day 1 AUC(0-24) (for both BID and once daily regimens). Accumulation ratio (RCmax)= Day 14 Cmax/Day 1 Cmax. RCmax was not computed for each dosing period (morning and evening).
Time frame: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose.
Population: PK Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | Cmax | 1.6438 Ratio |
| Part A | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | AUC (0-24) | 2.0619 Ratio |
| Part A | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | AUC (0-10) | 2.7380 Ratio |
| GSK1292263 75 mg | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | Cmax | 1.3137 Ratio |
| GSK1292263 75 mg | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | AUC (0-10) | 1.9230 Ratio |
| GSK1292263 75 mg | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | AUC (0-24) | 1.5528 Ratio |
| GSK1292263 300 mg | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | Cmax | 1.1077 Ratio |
| GSK1292263 300 mg | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | AUC (0-10) | NA Ratio |
| GSK1292263 300 mg | Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) | AUC (0-24) | 1.3730 Ratio |
Primary
Mean Post Meal Glucose Value (Part B)
Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner.
Time frame: At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Population: PD Population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 2 hour | 10.83 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1.5 hour | 12.56 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 3 hour | 11.05 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1 hour | 13.62 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1 hour | 9.61 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 0.5 hour | 13.75 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 2 hour | 11.42 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 0.5 hour | 14.16 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 0.5 hour | 7.43 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 3 hour | 7.78 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1.5 hour | 10.38 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 0.5 hour | 8.17 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1 hour | 11.07 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 0.5 hour | 7.46 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1.5 hour | 11.45 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 3 hour | 7.56 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1 hour | 10.31 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1.5 hour | 11.65 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 3 hour | 11.58 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 0.5 hour | 9.28 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 2 hour | 11.15 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1.5 hour | 11.07 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 3 hour | 10.43 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 2 hour | 10.71 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 2 hour | 11.67 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1.5 hour | 12.69 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 2 hour | 11.31 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1 hour | 11.15 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 3 hour | 10.51 mmol/L |
| Part A | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1 hour | 14.02 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 0.5 hour | 8.73 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 3 hour | 10.41 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 0.5 hour | 9.19 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1.5 hour | 10.97 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1 hour | 13.32 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1 hour | 11.27 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 2 hour | 10.51 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 3 hour | 10.05 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1 hour | 11.20 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 2 hour | 10.76 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 0.5 hour | 13.13 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1.5 hour | 10.80 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1 hour | 10.59 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1.5 hour | 11.81 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 2 hour | 11.27 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 3 hour | 9.78 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1 hour | 13.42 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 0.5 hour | 13.51 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1.5 hour | 12.12 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 2 hour | 10.55 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 0.5 hour | 7.99 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 3 hour | 8.48 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 3 hour | 6.96 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 0.5 hour | 8.90 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1 hour | 11.19 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 3 hour | 9.71 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 2 hour | 9.98 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1.5 hour | 11.17 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1.5 hour | 11.58 mmol/L |
| GSK1292263 75 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 2 hour | 10.82 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 2 hour | 11.50 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 0.5 hour | 8.56 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 3 hour | 11.25 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 0.5 hour | 14.96 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1 hour | 14.48 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1.5 hour | 12.94 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 0.5 hour | 14.68 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 3 hour | 8.68 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1 hour | 10.71 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1.5 hour | 11.64 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 2 hour | 11.75 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 0.5 hour | 8.78 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1 hour | 11.00 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1.5 hour | 10.99 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 2 hour | 10.81 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 3 hour | 10.34 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1 hour | 14.23 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1.5 hour | 12.96 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 2 hour | 10.93 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 3 hour | 8.20 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 0.5 hour | 10.07 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1 hour | 11.96 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1.5 hour | 12.33 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 2 hour | 12.09 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 3 hour | 10.57 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 0.5 hour | 9.37 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1 hour | 12.21 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1.5 hour | 13.01 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 2 hour | 12.07 mmol/L |
| GSK1292263 300 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 3 hour | 10.69 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 2 hour | 10.11 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 2 hour | 12.60 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1 hour | 14.32 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1.5 hour | 10.45 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1.5 hour | 13.07 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1 hour | 10.12 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 2 hour | 11.11 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 3 hour | 8.46 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1 hour | 12.56 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 3 hour | 8.73 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 2 hour | 10.67 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 0.5 hour | 8.70 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1.5 hour | 12.02 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1.5 hour | 13.03 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1 hour | 10.42 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 0.5 hour | 10.41 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1.5 hour | 11.12 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 0.5 hour | 8.58 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 0.5 hour | 13.04 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 2 hour | 10.87 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 3 hour | 11.75 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 3 hour | 10.44 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1 hour | 10.77 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 0.5 hour | 8.92 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1.5 hour | 10.94 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 2 hour | 10.98 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 3 hour | 10.37 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1 hour | 13.43 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 3 hour | 10.48 mmol/L |
| GSK1292263 600 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 0.5 hour | 13.83 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 0.5 hour | 8.39 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1.5 hour | 10.41 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 3 hour | 9.66 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1 hour | 12.03 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1.5 hour | 10.69 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1.5 hour | 8.83 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 0.5 hour | 13.60 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 2 hour | 10.18 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 1.5 hour | 10.55 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 1 hour | 10.36 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 3 hour | 8.90 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 2 hour | 10.07 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 2 hour | 10.72 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 2 hour | 9.10 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 0.5 hour | 7.93 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1.5 hour | 10.52 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 2 hour | 8.84 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 3 hour | 7.73 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 3 hour | 6.69 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 2 hour | 9.75 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1.5 hour | 11.39 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 3 hour | 8.80 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-breakfast, 1 hour | 13.12 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 0.5 hour | 7.77 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-breakfast, 0.5 hour | 12.26 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 1 hour | 9.43 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-dinner, 1 hour | 10.27 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day -1, post-lunch, 3 hour | 9.92 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-lunch, 1 hour | 8.38 mmol/L |
| Sitagliptin 50 mg | Mean Post Meal Glucose Value (Part B) | Day 14, post-dinner, 0.5 hour | 7.29 mmol/L |
Primary
Mean Post Meal Insulin Value (Part B)
Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner.
Time frame: At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.
Population: PD Population.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1 hour | 193.80 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1.5 hour | 204.67 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 3 hour | 191.74 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1 hour | 199.54 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 2 hour | 209.64 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1.5 hour | 188.57 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 0.5 hour | 153.65 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 3 hour | 131.95 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 3 hour | 200.85 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 0.5 hour | 135.17 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 0.5 hour | 201.81 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 3 hour | 176.48 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1 hour | 204.76 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 3 hour | 219.31 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 3 hour | 161.67 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1 hour | 222.44 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 2 hour | 235.41 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1.5 hour | 195.55 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 0.5 hour | 258.61 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 2 hour | 283.85 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1.5 hour | 251.01 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 2 hour | 237.34 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 0.5 hour | 99.41 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 2 hour | 237.14 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1.5 hour | 297.57 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 2 hour | 233.85 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1 hour | 201.54 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 0.5 hour | 132.04 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1.5 hour | 229.56 pmol/L |
| Part A | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1 hour | 304.23 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 2 hour | 220.97 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 3 hour | 114.67 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 0.5 hour | 240.43 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 0.5 hour | 115.21 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 0.5 hour | 98.57 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1 hour | 193.65 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 3 hour | 164.28 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1.5 hour | 208.37 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 2 hour | 196.74 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 3 hour | 171.15 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 2 hour | 205.06 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 0.5 hour | 131.50 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 3 hour | 181.43 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 3 hour | 167.22 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 2 hour | 214.66 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1 hour | 169.74 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1.5 hour | 194.93 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 0.5 hour | 129.25 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1.5 hour | 210.90 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1 hour | 205.59 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1 hour | 178.38 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 0.5 hour | 185.34 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 3 hour | 110.81 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1 hour | 258.37 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 2 hour | 234.65 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1.5 hour | 246.76 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1.5 hour | 183.16 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1.5 hour | 299.22 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 2 hour | 221.27 pmol/L |
| GSK1292263 75 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1 hour | 280.93 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 3 hour | 207.00 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 0.5 hour | 150.10 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1 hour | 226.22 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1.5 hour | 206.80 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 2 hour | 206.16 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 3 hour | 162.58 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1.5 hour | 212.29 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1.5 hour | 179.44 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 3 hour | 137.67 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1.5 hour | 163.94 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 2 hour | 168.71 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1 hour | 186.02 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 0.5 hour | 270.35 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1 hour | 296.05 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1.5 hour | 318.38 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 2 hour | 258.69 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 0.5 hour | 147.60 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 2 hour | 218.67 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 3 hour | 172.36 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 0.5 hour | 241.13 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1 hour | 297.58 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1.5 hour | 272.63 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 2 hour | 229.72 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 3 hour | 122.31 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 0.5 hour | 126.26 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1 hour | 172.43 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 2 hour | 177.88 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 0.5 hour | 75.85 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1 hour | 141.59 pmol/L |
| GSK1292263 300 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 3 hour | 134.98 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1.5 hour | 215.57 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 0.5 hour | 264.15 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 0.5 hour | 187.22 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 3 hour | 180.43 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 3 hour | 270.43 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 2 hour | 227.81 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 2 hour | 223.18 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 2 hour | 266.34 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 3 hour | 195.64 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 3 hour | 188.31 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1.5 hour | 409.93 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1.5 hour | 275.17 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 2 hour | 304.66 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 0.5 hour | 137.16 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1.5 hour | 223.72 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1 hour | 348.37 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1 hour | 274.72 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 3 hour | 191.01 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 0.5 hour | 169.17 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 2 hour | 295.21 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1 hour | 338.58 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1.5 hour | 289.19 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1 hour | 191.90 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 3 hour | 225.12 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 0.5 hour | 207.99 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1 hour | 246.08 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 2 hour | 333.39 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1 hour | 190.65 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 0.5 hour | 259.89 pmol/L |
| GSK1292263 600 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1.5 hour | 351.10 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 0.5 hour | 268.74 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 0.5 hour | 104.16 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1 hour | 354.57 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1.5 hour | 237.46 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 1.5 hour | 300.33 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 1 hour | 251.79 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 2 hour | 246.53 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 0.5 hour | 219.24 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-breakfast, 3 hour | 117.21 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1.5 hour | 179.94 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 2 hour | 187.66 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 0.5 hour | 155.68 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 0.5 hour | 109.63 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 3 hour | 167.37 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1 hour | 164.53 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 1.5 hour | 184.69 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 2 hour | 188.61 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 2 hour | 171.94 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-lunch, 3 hour | 172.22 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1.5 hour | 171.08 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 3 hour | 175.02 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 0.5 hour | 92.78 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 1 hour | 149.94 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 2 hour | 202.47 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1.5 hour | 173.21 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-lunch, 1 hour | 180.49 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-dinner, 3 hour | 155.62 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 3 hour | 106.98 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day 14, post-dinner, 1 hour | 156.48 pmol/L |
| Sitagliptin 50 mg | Mean Post Meal Insulin Value (Part B) | Day -1, post-breakfast, 2 hour | 196.53 pmol/L |
Primary
Mean Value of Urine Albumin at Follow up (Part A)
Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urine albumin was assessed using quantitative analysis.
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Part A | Mean Value of Urine Albumin at Follow up (Part A) | 6.0 milligrams per liter (mg/L) |
Primary
Mean Value of Urine Albumin (Part B)
Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urine albumin was assessed using quantitative analysis.
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Mean Value of Urine Albumin (Part B) | Day 1, pre-breakfast | 15.3 mg/L | Standard Deviation 11.3 |
| Part A | Mean Value of Urine Albumin (Part B) | Day 7, pre-breakfast | 8.0 mg/L | Standard Deviation 1.73 |
| Part A | Mean Value of Urine Albumin (Part B) | Day 14, 24 hours | 7.8 mg/L | Standard Deviation 2.5 |
| Part A | Mean Value of Urine Albumin (Part B) | Follow up | 54.0 mg/L | Standard Deviation 78.01 |
| GSK1292263 75 mg | Mean Value of Urine Albumin (Part B) | Day 1, pre-breakfast | 17.7 mg/L | Standard Deviation 11.5 |
| GSK1292263 75 mg | Mean Value of Urine Albumin (Part B) | Follow up | 26.1 mg/L | Standard Deviation 35.34 |
| GSK1292263 75 mg | Mean Value of Urine Albumin (Part B) | Day 7, pre-breakfast | 19.5 mg/L | Standard Deviation 27.67 |
| GSK1292263 75 mg | Mean Value of Urine Albumin (Part B) | Day 14, 24 hours | 28.3 mg/L | Standard Deviation 34.53 |
| GSK1292263 300 mg | Mean Value of Urine Albumin (Part B) | Follow up | 17.6 mg/L | Standard Deviation 13.87 |
| GSK1292263 300 mg | Mean Value of Urine Albumin (Part B) | Day 7, pre-breakfast | 24.5 mg/L | Standard Deviation 20.51 |
| GSK1292263 300 mg | Mean Value of Urine Albumin (Part B) | Day 14, 24 hours | 11.4 mg/L | Standard Deviation 6.31 |
| GSK1292263 300 mg | Mean Value of Urine Albumin (Part B) | Day 1, pre-breakfast | 8.7 mg/L | Standard Deviation 5.51 |
| GSK1292263 600 mg | Mean Value of Urine Albumin (Part B) | Day 1, pre-breakfast | 15.7 mg/L | Standard Deviation 8.33 |
| GSK1292263 600 mg | Mean Value of Urine Albumin (Part B) | Day 7, pre-breakfast | 24.0 mg/L | Standard Deviation 22.6 |
| GSK1292263 600 mg | Mean Value of Urine Albumin (Part B) | Follow up | 29.5 mg/L | Standard Deviation 34.65 |
| GSK1292263 600 mg | Mean Value of Urine Albumin (Part B) | Day 14, 24 hours | 11.0 mg/L | Standard Deviation 3.56 |
| Sitagliptin 50 mg | Mean Value of Urine Albumin (Part B) | Follow up | 11.2 mg/L | Standard Deviation 5.17 |
| Sitagliptin 50 mg | Mean Value of Urine Albumin (Part B) | Day 14, 24 hours | 10.4 mg/L | Standard Deviation 8.88 |
| Sitagliptin 50 mg | Mean Value of Urine Albumin (Part B) | Day 7, pre-breakfast | 7.3 mg/L | Standard Deviation 1.53 |
| Sitagliptin 50 mg | Mean Value of Urine Albumin (Part B) | Day 1, pre-breakfast | 6.6 mg/L | Standard Deviation 0.89 |
Primary
Mean Value of Urine pH (Part A)
Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is 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.
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Mean Value of Urine pH (Part A) | Day 1, 24 hours | 6.17 pH | Standard Deviation 0.258 |
| Part A | Mean Value of Urine pH (Part A) | Follow up | 5.92 pH | Standard Deviation 0.376 |
Primary
Mean Value of Urine pH (Part B)
Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is 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.
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Mean Value of Urine pH (Part B) | Day 14, 24 hours | 5.96 pH | Standard Deviation 0.414 |
| Part A | Mean Value of Urine pH (Part B) | Day 7, pre-breakfast | 6.11 pH | Standard Deviation 0.446 |
| Part A | Mean Value of Urine pH (Part B) | Day 1, pre-breakfast | 6.04 pH | Standard Deviation 0.499 |
| Part A | Mean Value of Urine pH (Part B) | Follow up | 6.15 pH | Standard Deviation 0.747 |
| GSK1292263 75 mg | Mean Value of Urine pH (Part B) | Day 1, pre-breakfast | 6.04 pH | Standard Deviation 0.431 |
| GSK1292263 75 mg | Mean Value of Urine pH (Part B) | Follow up | 5.88 pH | Standard Deviation 0.483 |
| GSK1292263 75 mg | Mean Value of Urine pH (Part B) | Day 7, pre-breakfast | 5.85 pH | Standard Deviation 0.24 |
| GSK1292263 75 mg | Mean Value of Urine pH (Part B) | Day 14, 24 hours | 6.04 pH | Standard Deviation 0.247 |
| GSK1292263 300 mg | Mean Value of Urine pH (Part B) | Day 14, 24 hours | 6.17 pH | Standard Deviation 0.326 |
| GSK1292263 300 mg | Mean Value of Urine pH (Part B) | Follow up | 5.96 pH | Standard Deviation 0.396 |
| GSK1292263 300 mg | Mean Value of Urine pH (Part B) | Day 1, pre-breakfast | 6.04 pH | Standard Deviation 0.257 |
| GSK1292263 300 mg | Mean Value of Urine pH (Part B) | Day 7, pre-breakfast | 6.00 pH | Standard Deviation 0.369 |
| GSK1292263 600 mg | Mean Value of Urine pH (Part B) | Day 14, 24 hours | 6.07 pH | Standard Deviation 0.267 |
| GSK1292263 600 mg | Mean Value of Urine pH (Part B) | Day 1, pre-breakfast | 6.03 pH | Standard Deviation 0.399 |
| GSK1292263 600 mg | Mean Value of Urine pH (Part B) | Day 7, pre-breakfast | 6.07 pH | Standard Deviation 0.458 |
| GSK1292263 600 mg | Mean Value of Urine pH (Part B) | Follow up | 6.08 pH | Standard Deviation 0.572 |
| Sitagliptin 50 mg | Mean Value of Urine pH (Part B) | Day 1, pre-breakfast | 5.92 pH | Standard Deviation 0.344 |
| Sitagliptin 50 mg | Mean Value of Urine pH (Part B) | Day 14, 24 hours | 6.08 pH | Standard Deviation 0.277 |
| Sitagliptin 50 mg | Mean Value of Urine pH (Part B) | Follow up | 5.88 pH | Standard Deviation 0.311 |
| Sitagliptin 50 mg | Mean Value of Urine pH (Part B) | Day 7, pre-breakfast | 6.04 pH | Standard Deviation 0.38 |
Primary
Mean Value of Urine Specific Gravity (Part A)
Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine .
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Mean Value of Urine Specific Gravity (Part A) | Day 1, 24 hours | 1.0150 Ratio | Standard Deviation 0.005 |
| Part A | Mean Value of Urine Specific Gravity (Part A) | Follow up | 1.0210 Ratio | Standard Deviation 0.00224 |
Primary
Mean Value of Urine Specific Gravity (Part B)
Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine .
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A | Mean Value of Urine Specific Gravity (Part B) | Day 1, pre-breakfast | 1.0127 Ratio | Standard Deviation 0.00518 |
| Part A | Mean Value of Urine Specific Gravity (Part B) | Day 7, pre-breakfast | 1.0144 Ratio | Standard Deviation 0.00464 |
| Part A | Mean Value of Urine Specific Gravity (Part B) | Day 14, 24 hours | 1.0170 Ratio | Standard Deviation 0.00587 |
| Part A | Mean Value of Urine Specific Gravity (Part B) | Follow up | 1.0200 Ratio | Standard Deviation 0.00661 |
| GSK1292263 75 mg | Mean Value of Urine Specific Gravity (Part B) | Day 1, pre-breakfast | 1.0144 Ratio | Standard Deviation 0.00417 |
| GSK1292263 75 mg | Mean Value of Urine Specific Gravity (Part B) | Follow up | 1.0163 Ratio | Standard Deviation 0.00443 |
| GSK1292263 75 mg | Mean Value of Urine Specific Gravity (Part B) | Day 14, 24 hours | 1.0161 Ratio | Standard Deviation 0.00651 |
| GSK1292263 75 mg | Mean Value of Urine Specific Gravity (Part B) | Day 7, pre-breakfast | 1.0177 Ratio | Standard Deviation 0.00564 |
| GSK1292263 300 mg | Mean Value of Urine Specific Gravity (Part B) | Day 1, pre-breakfast | 1.0125 Ratio | Standard Deviation 0.00418 |
| GSK1292263 300 mg | Mean Value of Urine Specific Gravity (Part B) | Follow up | 1.0185 Ratio | Standard Deviation 0.00669 |
| GSK1292263 300 mg | Mean Value of Urine Specific Gravity (Part B) | Day 7, pre-breakfast | 1.0150 Ratio | Standard Deviation 0.00447 |
| GSK1292263 300 mg | Mean Value of Urine Specific Gravity (Part B) | Day 14, 24 hours | 1.0143 Ratio | Standard Deviation 0.00607 |
| GSK1292263 600 mg | Mean Value of Urine Specific Gravity (Part B) | Day 14, 24 hours | 1.0127 Ratio | Standard Deviation 0.0041 |
| GSK1292263 600 mg | Mean Value of Urine Specific Gravity (Part B) | Day 1, pre-breakfast | 1.0132 Ratio | Standard Deviation 0.00513 |
| GSK1292263 600 mg | Mean Value of Urine Specific Gravity (Part B) | Day 7, pre-breakfast | 1.0125 Ratio | Standard Deviation 0.0038 |
| GSK1292263 600 mg | Mean Value of Urine Specific Gravity (Part B) | Follow up | 1.0172 Ratio | Standard Deviation 0.00618 |
| Sitagliptin 50 mg | Mean Value of Urine Specific Gravity (Part B) | Day 7, pre-breakfast | 1.0141 Ratio | Standard Deviation 0.00539 |
| Sitagliptin 50 mg | Mean Value of Urine Specific Gravity (Part B) | Day 14, 24 hours | 1.0138 Ratio | Standard Deviation 0.00433 |
| Sitagliptin 50 mg | Mean Value of Urine Specific Gravity (Part B) | Follow up | 1.0165 Ratio | Standard Deviation 0.00669 |
| Sitagliptin 50 mg | Mean Value of Urine Specific Gravity (Part B) | Day 1, pre-breakfast | 1.0135 Ratio | Standard Deviation 0.0058 |
Primary
Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part A)
Blood samples for chemistry assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Clinical chemistry parameter: Glucose (unit: millimoles per liter \[mmol/L\]) was assessed for abnormal high value of PCI. The normal range was 3.6 to 5.5 mmol/L
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part A) | 1 Participants |
Primary
Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B)
Blood samples for chemistry assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Clinical chemistry parameters: Aspartate amino transferase (unit: international unit per liter \[IU/L\]) and Total bilirubin (unit: micromoles per liter (µmol/L) were assessed for abnormal values of PCI. For aspartate aminotransferase the PCI range was \>=2 x ULN (high). For total bilirubin the PCI range was \>=1.5 x ULN (high).
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Aspartate aminotransferase, high | 0 Participants |
| Part A | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Total bilirubin, high | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Aspartate aminotransferase, high | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Total bilirubin, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Aspartate aminotransferase, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Total bilirubin, high | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Total bilirubin, high | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Aspartate aminotransferase, high | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Aspartate aminotransferase, high | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) | Total bilirubin, high | 1 Participants |
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A)
ECGs were taken at Screening, pre-breakfast on Day -1, on Day 1 (pre-breakfast, 1 hour, 2, 3, 4, 6, 8, 13, 24hours post-dose), and at follow-up. Assessments were made in triplicate on Day 1 at the pre-breakfast time point, and single assessments were made at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS).
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, pre-breakfast 1, abnormal-NCS | 3 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, pre-breakfast 2, abnormal-NCS | 2 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, pre-breakfast 3, abnormal-NCS | 2 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, 1 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, 2 hour, abnormal-NCS | 3 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, 3 hour, abnormal-NCS | 3 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, 4 hour, abnormal-NCS | 2 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, 6 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, 8 hour, abnormal-NCS | 3 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, 13 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) | Day 1, 24 hour, abnormal-NCS | 2 Participants |
Primary
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B)
ECGs were taken at Screening, pre-breakfast on Day -1 and at Follow-up. On Days 1, 7 and 14 ECGs were taken pre-breakfast (fasting) and at 1, 2, 4, 6, 8, 12 and 24hours post-dose. Triplicate ECGs were taken at the pre-breakfast time point, and single assessments were taken at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS).
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 4 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 24 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 6 hour, abnormal-NCS | 0 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 12 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 12 hour, abnormal-NCS | 2 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 6 hour, abnormal-NCS | 2 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 1, abnormal-NCS | 2 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 2, abnormal-NCS | 2 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 3, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 8 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 4 hour, abnormal-NCS | 0 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 2, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 1 hour, abnormal-NCS | 0 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 24 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 6 hour, abnormal-NCS | 0 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 24 hour, abnormal-NCS | 3 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 3, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 2 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 2, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 4 hour, abnormal-NCS | 0 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 1, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 1 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Follow up-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 2 hour, abnormal-NCS | 0 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 8 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-CS | 0 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 8 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 12 hour, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 3, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 1, abnormal-NCS | 1 Participants |
| Part A | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 2 hour, abnormal-NCS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 1 hour, abnormal-NCS | 3 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 4 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 1, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 4 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 24 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 6 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 12 hour, abnormal-NCS | 3 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 8 hour, abnormal-NCS | 4 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 3, abnormal-NCS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 3, abnormal-NCS | 3 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 2 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 2, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 1, abnormal-NCS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 6 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 8 hour, abnormal-NCS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 24 hour, abnormal-NCS | 3 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 12 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 12 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 8 hour, abnormal-NCS | 4 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 1, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 2 hour, abnormal-NCS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 6 hour, abnormal-NCS | 3 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 2, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 4 hour, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 3, abnormal-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 24 hour, abnormal-NCS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 2 hour, abnormal-NCS | 3 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-NCS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 1 hour, abnormal-NCS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-CS | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Follow up-NCS | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 2, abnormal-NCS | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 4 hour, abnormal-NCS | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 6 hour, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 12 hour, abnormal-NCS | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Follow up-NCS | 2 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 2, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 3, abnormal-NCS | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 1, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 8 hour, abnormal-NCS | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 24 hour, abnormal-NCS | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 1, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 2, abnormal-NCS | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 3, abnormal-NCS | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-CS | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 2 hour, abnormal-NCS | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 4 hour, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 6 hour, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 8 hour, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 12 hour, abnormal-NCS | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 24 hour, abnormal-NCS | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 1, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 1 hour, abnormal-NCS | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 2 hour, abnormal-NCS | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 6 hour, abnormal-NCS | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 4 hour, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 8 hour, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 12 hour, abnormal-NCS | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 24 hour, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 2, abnormal-NCS | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 3, abnormal-NCS | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 1 hour, abnormal-NCS | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 2 hour, abnormal-NCS | 4 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 2, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 2 hour, abnormal-NCS | 4 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-CS | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 1 hour, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-NCS | 6 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 1 hour, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 2 hour, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 3, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 4 hour, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 2, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 6 hour, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 1, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 8 hour, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 24 hour, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 4 hour, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 12 hour, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 8 hour, abnormal-NCS | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 2 hour, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 24 hour, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 2, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 1, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 3, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 1, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 6 hour, abnormal-NCS | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 3, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 8 hour, abnormal-NCS | 4 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 12 hour, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 6 hour, abnormal-NCS | 4 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Follow up-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 24 hour, abnormal-NCS | 3 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 4 hour, abnormal-NCS | 4 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 12 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 3, abnormal-NCS | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 1, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 24 hour, abnormal-NCS | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-CS | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 2, abnormal-NCS | 2 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 12 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 1 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 4 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 12 hour, abnormal-NCS | 2 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 1 hour, abnormal-NCS | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 12 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 3, abnormal-NCS | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 2 hour, abnormal-NCS | 2 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 1 hour, abnormal-NCS | 2 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 8 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 2 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 24 hour, abnormal-NCS | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 2, abnormal-NCS | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 8 hour, abnormal-NCS | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 4 hour, abnormal-NCS | 2 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 4 hour, abnormal-NCS | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 1, abnormal-NCS | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, pre-breakfast 1, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 1, 6 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 6 hour, abnormal-NCS | 5 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, pre-breakfast 3, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Follow up-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 6 hour, abnormal-NCS | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 2 hour, abnormal-NCS | 2 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 7, 8 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, 24 hour, abnormal-NCS | 3 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) | Day 14, pre-breakfast 2, abnormal-NCS | 4 Participants |
Primary
Number of Participants With Abnormal Hematology Values of PCI (Part B)
Blood samples for hematology assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Hematology parameters: Hematocrit (unit: ratio) and hemoglobin (unit: grams per liter \[g/L\]), were assessed for abnormal values of PCI. The PCI range for hematocrit was: \>0.075 decrease from Baseline (low), \>1.02 x upper limit normal (ULN) (high-male), \>1.17 x ULN (high-female). The PCI range for hemoglobin was: \>25 decrease from Baseline (low), \>1.03 x ULN (high-male), \>1.13 x ULN (high-female). Data has been presented for the number of participants with hematology data values high from the PCI range in a consolidated format.
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hematocrit, high | 0 Participants |
| Part A | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hemoglobin, high | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hematocrit, high | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hemoglobin, high | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hematocrit, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hemoglobin, high | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hemoglobin, high | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hematocrit, high | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hematocrit, high | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Hematology Values of PCI (Part B) | Hemoglobin, high | 1 Participants |
Primary
Number of Participants With Abnormal Hematology Values of Potential Clinical Importance (PCI) (Part A)
Blood samples for hematology assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Hematology parameter: Total Neutrophil count was assessed for abnormal value of PCI. The range of PCI value was: \<0.83 x lower limit normal (LLN) with unit x10\^9 per liter
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A | Number of Participants With Abnormal Hematology Values of Potential Clinical Importance (PCI) (Part A) | 1 Participants |
Primary
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A)
Urinalysis parameters: Urine occult blood, Urine Glucose, Urine ketones and Urine protein were assessed for abnormal findings by dipstick analysis. The abnormalities were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome.
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Urine occult blood, Day 1, 24 hours, trace | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Urine occult blood, follow up, trace | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Urine glucose, Day 1, 24 hours, 3+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Urine glucose, follow up, 3+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Urine glucose, follow up, trace | 2 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Urine ketones, follow up, trace | 2 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Urine protein, Day 1, 24 hours, trace | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) | Urine protein, follow up, trace | 2 Participants |
Primary
Number of Participants With Abnormal Urinalysis Data Values (Part B)
Urinalysis parameters: Urine occult blood, Urine glucose, Urine ketones, Urine protein, White blood cells were assessed for abnormal findings by dipstick analysis. The abnormal findings were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome.
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, trace | 2 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 1, pre-breakfast, trace | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, 1+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, trace | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 14, 24 hours, trace | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, 1+ | 2 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 1+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 2+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 2+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 1+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, trace | 3 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 2+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, trace | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 1+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 3+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, trace | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 1+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, 3+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, trace | 5 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 2+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, trace | 2 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, trace | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 7, pre-breakfast, trace | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, 3+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, 1+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, trace | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 1+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 2+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 3+ | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, trace | 1 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, trace | 2 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 14, 24 hours, trace | 2 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 1, pre-breakfast, trace | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 7, pre-breakfast, trace | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, 1+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 14, 24 hours, trace | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, 1+ | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, trace | 0 Participants |
| Part A | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, follow up, trace | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, 1+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 3+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, trace | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, trace | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, trace | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 1, pre-breakfast, trace | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 14, 24 hours, trace | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 2+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 2+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 7, pre-breakfast, trace | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, trace | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, 1+ | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, 3+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 7, pre-breakfast, trace | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, trace | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, follow up, trace | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, trace | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 14, 24 hours, trace | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 1+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, 3+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 2+ | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 1, pre-breakfast, trace | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, trace | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, 1+ | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, trace | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 14, 24 hours, trace | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 3+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 1+ | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 2+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, trace | 3 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, trace | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, trace | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 1+ | 1 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, trace | 2 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 2+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 14, 24 hours, trace | 2 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, trace | 4 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 3+ | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, 1+ | 2 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, trace | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, 1+ | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 2+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, trace | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, trace | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 1, pre-breakfast, trace | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 2+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, 1+ | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 1, pre-breakfast, trace | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, trace | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 2+ | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 2+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, trace | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, 1+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, follow up, trace | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, trace | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, trace | 2 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 7, pre-breakfast, trace | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 1+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 14, 24 hours, trace | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 2+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, 3+ | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 14, 24 hours, trace | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, trace | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, 3+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, trace | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, trace | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 7, pre-breakfast, trace | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, trace | 2 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 1+ | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 1+ | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 3+ | 4 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, 1+ | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, 3+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, trace | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 7, pre-breakfast, trace | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 14, 24 hours, trace | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, follow up, trace | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 2+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 3+ | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, trace | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 2+ | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, trace | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, 3+ | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, trace | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 2+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 3+ | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, trace | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 1, pre-breakfast, trace | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 7, pre-breakfast, trace | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 14, 24 hours, trace | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 1, pre-breakfast, trace | 2 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, trace | 4 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, trace | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 14, 24 hours, trace | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 2+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, trace | 4 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, trace | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, trace | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, trace | 1 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 1+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 2+ | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 14, 24 hours, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 7, pre-breakfast, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, trace | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 7, pre-breakfast, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, Day 1, pre-breakfast, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, trace | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 3+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 2+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 2+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 7, pre-breakfast, trace | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 14, 24 hours, 3+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 2+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, 1+ | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 7, pre-breakfast, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, trace | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 3+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 1, pre-breakfast, 3+ | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 14, 24 hours, trace | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 2+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, Day 1, pre-breakfast, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine glucose, follow up, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, follow up, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 2+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, follow up, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, follow up, trace | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 14, 24 hours, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 7, pre-breakfast, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine protein, Day 1, pre-breakfast, trace | 1 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine occult blood, Day 14, 24 hours, trace | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | White blood cells, Day 1, pre-breakfast, 1+ | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Urinalysis Data Values (Part B) | Urine ketones, follow up, trace | 0 Participants |
Primary
Number of Participants With Abnormal Vital Signs of PCI (Part A)
Assessment of vital signs (including systolic, diastolic blood pressure and heart rate) was performed at one time point at Screening, at follow-up and pre-breakfast on Day -1. On Day 1, they were taken at pre-breakfast, 1 hour, 3, 4, 6, 10, 16 and 24 hours post-dose. Assessments were made in triplicate at the pre-breakfast time point, and single assessments were made at all other times. Assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. PCI value of systolic blood pressure: \<85 and \>160 millimeter of mercury (mmHg). PCI value of diastolic blood pressure: \<45 and \>100 mmHg. PCI value of heart rate: \<40 and \>110 beats per minute.
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Abnormal Vital Signs of PCI (Part A) | Blood pressure (systolic and diastolic) | 0 Participants |
| Part A | Number of Participants With Abnormal Vital Signs of PCI (Part A) | Heart rate, high | 1 Participants |
Primary
Number of Participants With Abnormal Vital Signs of PCI (Part B)
Assessment of vital signs (including systolic and diastolic blood pressure and heart rate) was performed at Screening, pre-breakfast on Days -1 to 14 in a fasting state early in the morning (prior to morning dosing on Days 1-14), and at Follow-up. On Days 1, 7 and 14, they were taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes.
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Systolic blood pressure, high | 0 Participants |
| Part A | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Heart rate | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Systolic blood pressure, high | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Heart rate | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Systolic blood pressure, high | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Heart rate | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Heart rate | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Systolic blood pressure, high | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Systolic blood pressure, high | 0 Participants |
| Sitagliptin 50 mg | Number of Participants With Abnormal Vital Signs of PCI (Part B) | Heart rate | 0 Participants |
Primary
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (Part A)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time frame: Up to 10 days after discharge (Day 2) in Part A
Population: Safety Population consisted of all participants enrolled in the study and who had received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (Part A) | Any AE | 0 Participants |
| Part A | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (Part A) | Any SAE | 0 Participants |
Primary
Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B)
An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a 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, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.
Time frame: Up to 10 days after discharge (Day 15) in Part B
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any AE | 2 Participants |
| Part A | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any SAE | 0 Participants |
| GSK1292263 75 mg | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any AE | 3 Participants |
| GSK1292263 75 mg | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any SAE | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any AE | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any SAE | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any SAE | 0 Participants |
| GSK1292263 600 mg | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any AE | 4 Participants |
| Sitagliptin 50 mg | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any AE | 5 Participants |
| Sitagliptin 50 mg | Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) | Any SAE | 0 Participants |
Primary
Number of Participants With Relationship Between GSK1292263 Drug Exposures and Pharmacodynamic Parameters (Part B)
Data was not collected for this outcome measure.
Time frame: At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose
Population: PD Population. No data was collected for this outcome measure.
Primary
T1/2 Following Repeat Dose of GSK1292263 (Part B)
Outcome measure was added with caveat as data permits. The data for T1/2 was not collected.
Time frame: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).
Population: PK population
Primary
Terminal Phase Half-life (t1/2) Following a Single Dose of GSK1292263 (Part A)
Outcome measure was added with caveat as data permits. The data for t1/2 was not collected.
Time frame: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Population: PK Population
Primary
Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B)
Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only.
Time frame: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 1 | 14.00 hour |
| Part A | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 7 | 4.00 hour |
| Part A | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 14 | 4.00 hour |
| Part A | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tlag, Day1 | 0.000 hour |
| GSK1292263 75 mg | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 7 | 4.00 hour |
| GSK1292263 75 mg | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 14 | 13.00 hour |
| GSK1292263 75 mg | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 1 | 14.00 hour |
| GSK1292263 75 mg | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tlag, Day1 | 0.000 hour |
| GSK1292263 300 mg | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 14 | 4.0 hour |
| GSK1292263 300 mg | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 7 | 4.00 hour |
| GSK1292263 300 mg | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tlag, Day1 | 0.000 hour |
| GSK1292263 300 mg | Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) | Tmax, Day 1 | 4.0 hour |
Primary
Volume of Distribution (V/F) (Part A)
Outcome measure was added with caveat as data permits. The data for V/F was not collected.
Time frame: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.
Population: PK Population