Dyslipidaemias, Dyslipidemias
Conditions
Keywords
Pharmacodynamics, Lipids, Dyslipidemia, Safety, GSK1292263, Ezetimibe, Statin, Pharmacokinetics, Tolerability, Atorvastatin
Brief summary
This study investigates the safety, pharmacokinetics and effects of GSK1292263 when taken alone or when co-dosed with atorvastatin to subjects with dyslipidemia.
Detailed description
This compound has been studied in healthy subjects and subjects with type II diabetes and is now being studied in subjects with dyslipidemia. Because many patients with dyslipidemia are on statins, it is important to study how GSK1292263 behaves when taken with a potent statin, atorvastatin. The cholesterol lowering drug, ezetimibe, is included for comparison.
Interventions
10mg
DRUG80mg atorvastatin
80mg
DRUGGSK1292263 Placebo
Placebo
DRUG100mg GSK1292263
100mg
DRUG300mg GSK1292263
300mg
DRUG800mg GSK1292263
800mg
DRUG10mg ezetimibe
10mg
OTHERWashout
No interventions - washout period
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Healthy adult males and females of non-child-bearing-potential, aged 18-75 years who is capable of giving informed consent. * A female subject is eligible to participate if she is of: * Non-childbearing potential defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea. In questionable cases, a blood sample with simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \<40 pg/ml (\<140 pmol/L) is confirmatory in the absence of a clear post-menopausal history. * Females on hormone replacement therapy (HRT) must discontinue HRT to allow confirmation of post-menopausal status prior to study enrollment. For most forms of HRT, at least 2-4 weeks will elapse between the cessation of therapy and the blood draw; this interval depends on the type and dosage of HRT. Following confirmation of their post-menopausal status, they can resume use of HRT during the study. * Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until seven days following the last dose. * Body weight \> 50 kg (110 pounds) and body mass index (BMI) between 19.0 and 39.0 (inclusive). * Part A: (i) Subjects who are on 80mg or 40mg atorvastatin for \>= 4 weeks and are tolerating the drug well, or (ii) Subjects not on lipid-modifying therapy who have a fasting low density lipoprotein cholesterol (LDLc) \>= 130mg/dL. * In Part B at Screening: Subjects who are on statins or Vytorin treatment for \>= 4 weeks. * Part B at the end of the 4 week washout: Subjects who have a fasting LDL cholesterol of \>=120mg/dL and \<=180mg/dL and fasting triglycerides of \>=100mg/dL and \<=400mg/dL. * Part B at the end of the 4 week run-in on atorvastatin: Subjects who are tolerating well atorvastatin 10mg or 80mg (as determined by the Investigator). * Part B: Subjects must be willing to discontinue statins or Vytorin for the duration of the study. * Liver enzymes, AST and ALT \< 2x upper limit of normal (ULN); 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. * Average QTcB or QTcF \< 450msec; or QTc \< 480msec in subjects with right bundle branch block.
Exclusion criteria
* A medical history of the following: * Clinical or angiographic cardiovascular disease, including history or current evidence of coronary heart disease, heart failure, cerebrovascular disease (including stroke and transient ischemic attack \[mini-stroke\]), peripheral vascular disease. Subjects pending diagnostic procedures for any of those conditions at the time of screening will not be eligible for participation. * Homozygous familial hypercholesterolemia or family history of familial hypercholesterolemia (Part B only). Note: Subjects with heterozygous familial hypercholesterolemia on 80mg atorvastatin who are tolerating this drug well and fulfill the other eligibility criteria may participate in Part A only. * History of recurrent or unexplained muscle aches (e.g., fibromyalgia), myopathy or myositis, whether or not it is related to treatment with statins or other lipid modifying drugs. * Renal impairment as defined by a calculated glomerular filtration rate \< 60 mL/min * History of diabetes mellitus, or history of post-prandial and/or random blood glucose \> 200 mg/dl or fasting glucose \> 125 mg/dL or currently taking diabetes medications to manage fasting glucose levels (e.g., thiazolidinediones, sulfonylureas, insulin, metformin). * History of pancreatitis within 10 years of screening. * Any concurrent serious illness (e.g., severe chronic obstructive pulmonary disease, sleep apnea, history of malignancy other than skin cancer within 5 years of initial diagnosis or with evidence of recurrence) that may interfere with a subject from completing the study. * Current or chronic history of liver disease, or known hepatic or biliary abnormalities. * Active peptic ulcer disease and/or history of peptic ulcer disease or gastrointestinal bleeding within 12 months prior to screening. * History of kidney stones within 10 years of screening. * History of uncorrected thyroid dysfunction or an abnormal thyroid function test assessed by thyroid stimulating hormone (TSH) at Screening. (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 3 months prior to screening and who have a screening TSH within the normal range may participate.) * 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 disease or malabsorption syndromes within the past year. * Gastrointestinal surgery that may affect the pharmacokinetics or pharmacodynamics of the study drugs. Note: Subjects may be enrolled in the study if they have had a cholecystectomy three or more months before the time of screening and are stable and asymptomatic. * Subjects taking ezetimibe monotherapy, fibrates, bile acid binding resins, nicotinic acid or fat absorption inhibitors are not eligible for Parts A and B. * For females a hemoglobin \< 11.5g/dL, and for males a hemoglobin \< 12.5g/dL. * Current inadequately controlled hypertension (blood pressure \>= 160mmHg systolic or \>= 100mmHg diastolic at screening). If blood pressure medication is changed as a result of screening, blood pressure will be re-measured after 6 weeks and must again meet these criteria. * Significant electrocardiogram (ECG) abnormalities, defined as follows: Heart Rate \< 50 and \>100bpm PR Interval \<120 and \> 220ms QRS duration \< 70 and \>120ms QTC Interval (Bazett) \> 450ms Or, has clinically significant rhythm abnormalities identified during 24-hour screening Holter assessment. Subjects with left bundle branch block are excluded from the study. Subjects with partial right bundle branch block may be considered for inclusion following consultation with the GlaxoSmithKline (GSK) Medical Monitor. Subjects with Wolf-Parkinson-White (WPW) syndrome are excluded from the study. * Creatinine phosphokinase (CPK) \>= 2x ULN at screening. * A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening. * A positive test for HIV antibody. * The subject has a positive pre-study drug-of-abuse screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines. * History of regular alcohol consumption within 6 months of the study defined as: An average weekly intake of \>14 drinks/week for men or \>7 drinks/week for women. One drink is equivalent to (12 g alcohol) = 5 ounces (150 ml) of wine or 12 ounces (360 ml) of beer or 1.5 ounces (45 ml) of 80 proof distilled spirits. * Subjects will be excluded if they require treatment with systemic corticosteroids. * Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) prior to dosing. * Exposure to more than four new chemical entities within 12 months prior to the first dosing day. * History of sensitivity or untoward reaction to the study medications (GSK1292263, atorvastatin or ezetimibe), or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. * History of intolerance to statins. * Any change in concomitant medication (including multivitamins, herbal remedies, dietary supplements, and over-the-counter medication) within six weeks prior to screening that is not approved by GSK. * On a diet that may affect study outcomes, or any change in diet, exercise habits or smoking status within six weeks prior to screening or planned change during study (e.g., new exercise program) other than that in the dietary instructions in the Study Procedures Manual. * 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, unless in the opinion of the Investigator and GSK Medical Monitor the medication will not interfere with the study procedures or compromise subject safety. * Where participation in study would result in donation of blood in excess of approximately 500mL within a 56 day period. * Subject is mentally or legally incapacitated. * Unwillingness or inability to follow the procedures outlined in the protocol. * Pregnant females as determined by positive urine hCG test at screening or prior to dosing. * Lactating females. * History of sensitivity to heparin or heparin-induced thrombocytopenia. * Consumption of red wine, Seville oranges, grapefruit or grapefruit juice and/or pummelos, exotic citrus fruits, grapefruit hybrids or fruit juices from 7 days prior to the first dose of study medication. * Unwilling to abstain from caffeine-or xanthine-containing products from Day -2 until Day 15. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | Baseline and Day 14 | Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was Day -1 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100. |
| AUC (0-24) of Atorvastatin- Part A | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). |
| AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). |
| Trough Concentration of Atorvastatin | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were planned to be collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were planned to be collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were planned to be collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was planned to be collected on Day 16). |
| Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Baseline and Day 14 | Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100. |
| Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | Baseline and Day 14 | Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100. |
| Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Baseline and Day 14 | Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100. |
| Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | Baseline and Day 14 | Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100. |
| Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A | Up to Day 26 | An AE is defined as any untoward medical occurrence in a 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, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury. |
| Number of Participants With Any AEs and SAEs- Part B (Washout) | Up to Day 28 | An AE is defined as any untoward medical occurrence in a 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, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury. |
| Number of Participants With Any AEs and SAEs- Part B (Run-in) | Up to Day 28 | An AE is defined as any untoward medical occurrence in a 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, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury. |
| Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Up to Day 26 | An AE is defined as any untoward medical occurrence in a 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, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury. |
| Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A | Up to Day 26 | Single ECGs were taken after admission on Day -1 and at Follow-up (up to Day 26). On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No value found to be abnormal clinically significant in Part A of the study. |
| Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout) | Up to Day 28 | ECGs were taken at Screening, and on Day1 and Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. |
| Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in) | Day 28 | ECGs were taken on Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No data found to be abnormal clinically significant in run-in phase. |
| Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | Up to Day 26 | Single ECGs were taken after admission on Day -2, and pre-breakfast on Days -1, 4, 10, and at Follow-up. On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. The data was found to be abnormal clinically significant in treatment phase. |
| Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A | Up to Day 26 | Assessment of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate was performed after admission on Day -1 and at Follow-up. On Days 1, 7 and 14, they were taken at pre-dose, 1, 3, 6, 8, 14 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. Data for only those parameters are presented for which findings are of PCI either high or low. |
| Number of Participants With Vital Signs of PCI- Part B (Washout) | Up to day 28 | Assessment of vital signs including SBP, DBP heart rate was performed at Screening, on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low. |
| Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in) | Up to day 28 | Assessment of vital signs including SBP, DBP and heart rate was performed on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low. |
| Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Up to Day 26 | Assessment of vital signs including SBP, DBP and heart rate was performed after admission on Day-2, and pre-breakfast on Days -1, 4, and 10 in a fasting state early in the morning (prior to dosing), and at Follow-up. On Days 1, 7 and 14, they were also be 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. Data for only those parameters are presented for which findings are of PCI either high or low. |
| Number of Participants With Abnormal Hematology Value of PCI- Part A | Up to Day 26 | Blood samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Data for only those parameters (Hematocrit, Hemoglobin and Total neutrophils) are presented for which findings are of PCI either high or low. |
| Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout) | Up to Day 28 | Blood samples were collected at screening, and on Days 1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (White blood cells \[WBC\], Total neutrophils, Hematocrit and Lymphocytes) are presented for which findings are of PCI either high or low. |
| Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in) | Days 14 and 28 | Blood samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Lymphocytes) are presented for which findings are of PCI either high or low. |
| Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Up to Day 26 | Blood samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24hrs post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24hrs post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Platelet count, Total neutrophils and Lymphocytes) are presented for which findings are of PCI either high or low. |
| Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A | Up to Day 26 | Samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). No parameter was found to have any value of PCI. |
| Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Up to Day 28 | Samples were collected at screening, and on Days1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Inorganic phosphorus, Sodium, Alanine aminotransferase \[ALT\], Potassium, Creatinine, Calcium, magnesium, Glucose, Total Bilirubin, Carbon dioxide/bicarbonate \[CO2/HCO3\] and Aspartate aminotransferase \[AST\]) are presented for which findings are of PCI either high or low. |
| Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Days 14 and 28 | Samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Glucose, Magnesium, ALT, AST, Calcium, Inorganic phosphorus and Total bilirubin) are presented for which findings are of PCI either high or low. |
| Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Up to Day 26 | Samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24 hours post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Glucose, Total bilirubin, Albumin, Magnesium, CO2/HCO3, Calcium, ALT, AST, Inorganic phosphorus, Potassium and Sodium) are presented for which findings are of PCI either high or low. |
| Maximum Observed Concentration (Cmax) of GSK1292263- Part A | On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | Serial blood samples for the determination of the PK for GSK1292263 on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1). |
| Cmax of GSK1292263- Part B (Pooled Treatment Arm) | On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16). |
| Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1). |
| Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A | On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | Serial blood samples for the determination of the PK for GSK1292263 on Days 1 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48h sample on Day 1). |
| Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16). |
| Tlag of GSK1292263- Part B (Pooled Treatment Arm) | On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. | Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. |
| Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A | On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1). |
| AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16). |
| Trough Concentration of GSK1292263 | On Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | Trough samples for GSK1292263 PK (all treatment arms) were planned to be collected early in the morning on Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48h PK sample was collected on Day 16). (pre-dose for Days 13 and 14; trough Day 15 = 24h post last dose; trough Day 16 = 48h post last dose). |
| Cmax of Atorvastatin- Part A | On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose. | Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1). |
| Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). |
| Tmax of Atorvastatin- Part A | On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose. | Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1). |
| Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). |
| Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose. | Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1). |
| Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose and on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). |
| AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose. | Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1). |
| AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). |
| Trough Concentration of Atorvastatin Metabolite (2-Hydroxyatorvastatin) | On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose | For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were supposed to collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were supposed to collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were supposed to collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). However no data was collected. |
| Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose. | Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1). |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 21 centers in the United States during the period 14 September 2010 to 29 June 2011. There were 6 total participants in Part A, then Part B started with total of 281 participants which flowed through the rest of the phases of the trial. Part B had washout phase and run-In phase followed by treatment phase.
Pre-assignment details
Total 130 participants were randomized and received at least one dose of study drug in the treatment period phase. Part B Run-In excludes those participants randomized to monotherapy arms; that is, these participant counts are only those who were receiving Atorvastatin.
Participants by arm
| Arm | Count |
|---|---|
| Part A Four participants on 80 mg atorvastatin \[either for \>=4 weeks prior to screening (80 mg), or for 2 weeks, if the dose was escalated from a stable dose of 40 mg\], received GSK1292263 800 mg for 2 weeks, and 2 participants not on lipid-modifying treatment received GSK1282263 800 mg alone for 2 weeks. | 6 |
| Part B Part B included Washout phase (Participants were washed off their prior lipid-lowering therapy for 4 weeks), Run-in phase (Eligible participants were randomized to receive 10 mg open-labeled atorvastatin or 80 mg open-labeled atorvastatin for a 4-week stabilization run-in period) and Treatment phase (Randomized participants after washout received monotherpy (100 mg, 300 mg or 800 mg of GSK1292263 or placebo) for 2 weeks. Participants in the 10mg atorvastatin run-in group received GSK1292263, 300 mg QD GSK1292263, 800 mg QD GSK1292263, placebo for GSK1292263 or 10 mg open-label ezetimibe for 2 weeks. Participants in the 80 mg atorvastatin run-in group received 800 mg QD GSK1292263 and placebo for GSK1292263 for 2 weeks) | 281 |
| Total | 287 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Part B Pooled Treatment Arm | Adverse Event | 0 | 0 | 0 | 2 |
| Part B Pooled Treatment Arm | Protocol Violation | 0 | 0 | 0 | 1 |
| Part B Run-in | Adverse Event | 0 | 0 | 1 | 0 |
| Part B Run-in | Protocol Violation | 0 | 0 | 2 | 0 |
| Part B Run-in | Withdrawal by Subject | 0 | 0 | 3 | 0 |
| Part B Washout | Adverse Event | 0 | 1 | 0 | 0 |
| Part B Washout | Did not meet continuation criteria | 0 | 112 | 0 | 0 |
| Part B Washout | Lost to Follow-up | 0 | 2 | 0 | 0 |
| Part B Washout | Physician Decision | 0 | 14 | 0 | 0 |
| Part B Washout | Reached defined stopping criteria | 0 | 2 | 0 | 0 |
| Part B Washout | Withdrawal by Subject | 0 | 14 | 0 | 0 |
Baseline characteristics
| Characteristic | Total | Part B | Part A |
|---|---|---|---|
| Age, Continuous | 49.2 Years STANDARD_DEVIATION 5.34 | 57.7 Years STANDARD_DEVIATION 9.97 | 49.2 Years STANDARD_DEVIATION 5.34 |
| Race/Ethnicity, Customized African American/African Heritage | 33 Participants | 32 Participants | 1 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Japanese Heritage | 2 Participants | 2 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed Race | 3 Participants | 3 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 7 Participants | 7 Participants | 0 Participants |
| Race/Ethnicity, Customized White - Mixed Race | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 235 Participants | 230 Participants | 5 Participants |
| Sex: Female, Male Female | 152 Participants | 152 Participants | 0 Participants |
| Sex: Female, Male Male | 135 Participants | 129 Participants | 6 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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk | EG016 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 2 | 0 / 281 | 0 / 281 | 0 / 62 | 0 / 27 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 13 | 0 / 12 | 0 / 13 | 0 / 11 | 0 / 12 | 0 / 13 | 0 / 11 |
| other Total, other adverse events | 0 / 4 | 2 / 2 | 14 / 281 | 37 / 281 | 19 / 62 | 8 / 27 | 6 / 11 | 2 / 11 | 3 / 11 | 3 / 12 | 4 / 13 | 6 / 12 | 4 / 13 | 5 / 11 | 7 / 12 | 8 / 13 | 4 / 11 |
| serious Total, serious adverse events | 0 / 4 | 0 / 2 | 0 / 281 | 0 / 281 | 0 / 62 | 0 / 27 | 0 / 11 | 0 / 11 | 0 / 11 | 0 / 12 | 0 / 13 | 0 / 12 | 0 / 13 | 0 / 11 | 0 / 12 | 0 / 13 | 0 / 11 |
Outcome results
Primary
Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A | Day 1 | 12953.89 nanograms hour per milliliter | Geometric Coefficient of Variation 16.976 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A | Day 14 | 13206.52 nanograms hour per milliliter | Geometric Coefficient of Variation 15.07 |
| 800 mg GSK1292263 | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A | Day 1 | 12032.21 nanograms hour per milliliter | — |
| 800 mg GSK1292263 | Area Under the Concentration-time Curve From Time Zero (Pre-dose) to 24 Hours [AUC(0-24)] of GSK1292263- Part A | Day 14 | 11890.40 nanograms hour per milliliter | Geometric Coefficient of Variation 5.73 |
Primary
AUC (0-24) of Atorvastatin- Part A
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part A | Day 14 | 187.25 nanograms hour per milliliter | Geometric Coefficient of Variation 52.566 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part A | Day -1 | 219.27 nanograms hour per milliliter | Geometric Coefficient of Variation 77.893 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part A | Day 1 | 199.15 nanograms hour per milliliter | Geometric Coefficient of Variation 73.974 |
Primary
AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 17.84 nanograms hour per milliliter | Geometric Coefficient of Variation 35.028 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 15.58 nanograms hour per milliliter | Geometric Coefficient of Variation 14.934 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 23.16 nanograms hour per milliliter | Geometric Coefficient of Variation 18.115 |
| 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 26.19 nanograms hour per milliliter | Geometric Coefficient of Variation 30.561 |
| 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 23.77 nanograms hour per milliliter | Geometric Coefficient of Variation 38.501 |
| 800 mg GSK1292263 | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 28.78 nanograms hour per milliliter | Geometric Coefficient of Variation 26.611 |
| Atorvastatin 10 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 20.41 nanograms hour per milliliter | Geometric Coefficient of Variation 70.602 |
| Atorvastatin 10 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 20.83 nanograms hour per milliliter | Geometric Coefficient of Variation 50.427 |
| Atorvastatin 10 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 19.26 nanograms hour per milliliter | Geometric Coefficient of Variation 54.767 |
| Atorvastatin 10 mg + Placebo | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 18.77 nanograms hour per milliliter | Geometric Coefficient of Variation 51.122 |
| Atorvastatin 10 mg + Placebo | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 19.33 nanograms hour per milliliter | Geometric Coefficient of Variation 55.62 |
| Atorvastatin 10 mg + Placebo | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 18.60 nanograms hour per milliliter | Geometric Coefficient of Variation 56.102 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 19.59 nanograms hour per milliliter | Geometric Coefficient of Variation 47.952 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 20.24 nanograms hour per milliliter | Geometric Coefficient of Variation 41.371 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 19.05 nanograms hour per milliliter | Geometric Coefficient of Variation 48.448 |
| Atorvastatin 80 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 188.88 nanograms hour per milliliter | Geometric Coefficient of Variation 70.744 |
| Atorvastatin 80 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 174.13 nanograms hour per milliliter | Geometric Coefficient of Variation 55.829 |
| Atorvastatin 80 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 174.93 nanograms hour per milliliter | Geometric Coefficient of Variation 59.199 |
| Atorvastatin 80 mg + Placebo | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 186.73 nanograms hour per milliliter | Geometric Coefficient of Variation 35.837 |
| Atorvastatin 80 mg + Placebo | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 188.31 nanograms hour per milliliter | Geometric Coefficient of Variation 54.02 |
| Atorvastatin 80 mg + Placebo | AUC (0-24) of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 173.62 nanograms hour per milliliter | Geometric Coefficient of Variation 31.333 |
Primary
AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 4218.02 nanograms hour per milliliter | Geometric Coefficient of Variation 54.264 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 4968.29 nanograms hour per milliliter | Geometric Coefficient of Variation 24.683 |
| 800 mg GSK1292263 | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 5373.78 nanograms hour per milliliter | Geometric Coefficient of Variation 64.021 |
| 800 mg GSK1292263 | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 7484.67 nanograms hour per milliliter | Geometric Coefficient of Variation 51.772 |
| Atorvastatin 10 mg + GSK1292263 800 mg | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 10384.24 nanograms hour per milliliter | Geometric Coefficient of Variation 15.165 |
| Atorvastatin 10 mg + GSK1292263 800 mg | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 11224.58 nanograms hour per milliliter | Geometric Coefficient of Variation 44.087 |
| Atorvastatin 10 mg + Placebo | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 9812.21 nanograms hour per milliliter | Geometric Coefficient of Variation 25.708 |
| Atorvastatin 10 mg + Placebo | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 10760.74 nanograms hour per milliliter | Geometric Coefficient of Variation 22.081 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 2753.61 nanograms hour per milliliter | Geometric Coefficient of Variation 48.535 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 4061.78 nanograms hour per milliliter | Geometric Coefficient of Variation 35.242 |
| Atorvastatin 80 mg + GSK1292263 800 mg | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 5342.77 nanograms hour per milliliter | Geometric Coefficient of Variation 18.108 |
| Atorvastatin 80 mg + GSK1292263 800 mg | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 6737.82 nanograms hour per milliliter | Geometric Coefficient of Variation 28.082 |
| Atorvastatin 80 mg + Placebo | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 8937.99 nanograms hour per milliliter | Geometric Coefficient of Variation 21.08 |
| Atorvastatin 80 mg + Placebo | AUC(0-24) of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 8837.31 nanograms hour per milliliter | Geometric Coefficient of Variation 79.003 |
Primary
Cmax of Atorvastatin- Part A
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Population: PK parameter Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin- Part A | Day -1 | 45.587 nanograms per milliliter | Geometric Coefficient of Variation 130.4168 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin- Part A | Day 1 | 25.867 nanograms per milliliter | Geometric Coefficient of Variation 88.8156 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin- Part A | Day 14 | 38.443 nanograms per milliliter | Geometric Coefficient of Variation 71.1418 |
Primary
Cmax of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 2.045 nanograms per milliliter | Geometric Coefficient of Variation 41.398 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 1.453 nanograms per milliliter | Geometric Coefficient of Variation 14.5258 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 1.292 nanograms per milliliter | Geometric Coefficient of Variation 26.6345 |
| 800 mg GSK1292263 | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 2.195 nanograms per milliliter | Geometric Coefficient of Variation 47.6989 |
| 800 mg GSK1292263 | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 2.454 nanograms per milliliter | Geometric Coefficient of Variation 34.682 |
| 800 mg GSK1292263 | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 2.154 nanograms per milliliter | Geometric Coefficient of Variation 69.0856 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 2.139 nanograms per milliliter | Geometric Coefficient of Variation 74.2524 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 1.683 nanograms per milliliter | Geometric Coefficient of Variation 54.1388 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 1.926 nanograms per milliliter | Geometric Coefficient of Variation 47.0899 |
| Atorvastatin 10 mg + Placebo | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 1.852 nanograms per milliliter | Geometric Coefficient of Variation 57.6472 |
| Atorvastatin 10 mg + Placebo | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 1.640 nanograms per milliliter | Geometric Coefficient of Variation 68.6754 |
| Atorvastatin 10 mg + Placebo | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 1.816 nanograms per milliliter | Geometric Coefficient of Variation 54.6608 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 2.003 nanograms per milliliter | Geometric Coefficient of Variation 73.2912 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 1.949 nanograms per milliliter | Geometric Coefficient of Variation 56.7747 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 1.872 nanograms per milliliter | Geometric Coefficient of Variation 64.1762 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 42.376 nanograms per milliliter | Geometric Coefficient of Variation 113.1276 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 38.419 nanograms per milliliter | Geometric Coefficient of Variation 71.2059 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 31.018 nanograms per milliliter | Geometric Coefficient of Variation 81.5136 |
| Atorvastatin 80 mg + Placebo | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 45.781 nanograms per milliliter | Geometric Coefficient of Variation 38.479 |
| Atorvastatin 80 mg + Placebo | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 37.058 nanograms per milliliter | Geometric Coefficient of Variation 47.559 |
| Atorvastatin 80 mg + Placebo | Cmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 41.092 nanograms per milliliter | Geometric Coefficient of Variation 73.0152 |
Primary
Cmax of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 361.595 nanograms per milliliter | Geometric Coefficient of Variation 25.9981 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 281.321 nanograms per milliliter | Geometric Coefficient of Variation 35.9671 |
| 800 mg GSK1292263 | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 475.297 nanograms per milliliter | Geometric Coefficient of Variation 36.5131 |
| 800 mg GSK1292263 | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 639.687 nanograms per milliliter | Geometric Coefficient of Variation 33.6608 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 808.278 nanograms per milliliter | Geometric Coefficient of Variation 20.0646 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 886.418 nanograms per milliliter | Geometric Coefficient of Variation 31.3931 |
| Atorvastatin 10 mg + Placebo | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 790.315 nanograms per milliliter | Geometric Coefficient of Variation 32.508 |
| Atorvastatin 10 mg + Placebo | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 848.082 nanograms per milliliter | Geometric Coefficient of Variation 25.1892 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 364.936 nanograms per milliliter | Geometric Coefficient of Variation 39.1918 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 263.279 nanograms per milliliter | Geometric Coefficient of Variation 43.014 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 590.949 nanograms per milliliter | Geometric Coefficient of Variation 20.7601 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 478.676 nanograms per milliliter | Geometric Coefficient of Variation 21.2079 |
| Atorvastatin 80 mg + Placebo | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 1 | 787.922 nanograms per milliliter | Geometric Coefficient of Variation 36.7864 |
| Atorvastatin 80 mg + Placebo | Cmax of GSK1292263- Part B (Pooled Treatment Arm) | Day 14 | 782.914 nanograms per milliliter | Geometric Coefficient of Variation 81.2992 |
Primary
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48h sample on Day 1).
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A | 0.250 hours |
| 800 mg GSK1292263 | Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of GSK1292263- Part A | 0.000 hours |
Primary
Maximum Observed Concentration (Cmax) of GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263 on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: Pharmacokinetic (PK) Parameter Population was defined as participants in the 'PK Concentration' population for whom PK parameters were derived. The 'PK Concentration Population' was defined as participants in the 'All Subjects' Population for whom a PK sample was obtained and analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Maximum Observed Concentration (Cmax) of GSK1292263- Part A | Day 1 | 976.335 nanograms per milliliter | Geometric Coefficient of Variation 16.6353 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Maximum Observed Concentration (Cmax) of GSK1292263- Part A | Day 14 | 1118.344 nanograms per milliliter | Geometric Coefficient of Variation 20.6141 |
| 800 mg GSK1292263 | Maximum Observed Concentration (Cmax) of GSK1292263- Part A | Day 1 | 986.811 nanograms per milliliter | Geometric Coefficient of Variation 46.4825 |
| 800 mg GSK1292263 | Maximum Observed Concentration (Cmax) of GSK1292263- Part A | Day 14 | 948.764 nanograms per milliliter | Geometric Coefficient of Variation 6.5356 |
Primary
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A
Samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). No parameter was found to have any value of PCI.
Time frame: Up to Day 26
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part A | 0 Participants |
Primary
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm)
Samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24 hours post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Glucose, Total bilirubin, Albumin, Magnesium, CO2/HCO3, Calcium, ALT, AST, Inorganic phosphorus, Potassium and Sodium) are presented for which findings are of PCI either high or low.
Time frame: Up to Day 26
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 2 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 2 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 1 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 2 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 1 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 1 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 1 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 1 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 1 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 1 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 1 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 2 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 1 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 1 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 2 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 1 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 3 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 1 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 2 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 3 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 1 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 1 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 2 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 1 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Potassium, low | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, high | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, high | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Total bilirubin, high | 1 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Albumin, low | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | CO2/HCO3, low | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Sodium, high | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Magnesium, high | 2 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, high | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | AST, high | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Glucose, low | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | ALT, high | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Inorganic phosphorus, high | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Pooled Treatment Arm) | Calcium, low | 0 Participants |
Primary
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in)
Samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Glucose, Magnesium, ALT, AST, Calcium, Inorganic phosphorus and Total bilirubin) are presented for which findings are of PCI either high or low.
Time frame: Days 14 and 28
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | ALT, high | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | AST, high | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Magnesium, high | 5 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Calcium, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Inorganic phosphorus, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Total bilirubin, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Glucose, high | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Total bilirubin, high | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Magnesium, high | 5 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Calcium, high | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | ALT, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | AST, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Inorganic phosphorus, low | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (run-in) | Glucose, high | 0 Participants |
Primary
Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout)
Samples were collected at screening, and on Days1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Inorganic phosphorus, Sodium, Alanine aminotransferase \[ALT\], Potassium, Creatinine, Calcium, magnesium, Glucose, Total Bilirubin, Carbon dioxide/bicarbonate \[CO2/HCO3\] and Aspartate aminotransferase \[AST\]) are presented for which findings are of PCI either high or low.
Time frame: Up to Day 28
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Inorganic phosphorus, low | 2 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Sodium, high | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Sodium, low | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | CO2/bicarbonate, low | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Creatinine, high | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Calcium, high | 2 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Magnesium, high | 32 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Glucose, low | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Total bilirubin, high | 6 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Inorganic phosphorus, high | 3 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | ALT, high | 3 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Potassium, high | 3 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Potassium, low | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | Glucose, high | 4 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinical Chemistry Value of PCI- Part B (Washout) | AST, high | 1 Participants |
Primary
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm)
Single ECGs were taken after admission on Day -2, and pre-breakfast on Days -1, 4, 10, and at Follow-up. On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. The data was found to be abnormal clinically significant in treatment phase.
Time frame: Up to Day 26
Population: All subjects Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
| Placebo | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Pooled Treatment Arm) | 0 Participants |
Primary
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in)
ECGs were taken on Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No data found to be abnormal clinically significant in run-in phase.
Time frame: Day 28
Population: All subjects Population. Only those participants present during Run in/Day 28 were evaluated/included.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in) | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Run-in) | 0 Participants |
Primary
Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout)
ECGs were taken at Screening, and on Day1 and Day 28. Single assessments were made. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings.
Time frame: Up to Day 28
Population: All subject Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout) | Day 1 | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Clinically Significant ECG Findings- Part B (Washout) | Day 28 | 1 Participants |
Primary
Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A
Single ECGs were taken after admission on Day -1 and at Follow-up (up to Day 26). On Days 1, 7, and 14 single ECGS were taken pre-breakfast (fasting) and at 1, 3, 6, 8, 14 and 24 hours post-dose. ECGs were taken in supine position. Additional ECGs were taken at the discretion of the investigator as needed based on symptoms or ECG findings. No value found to be abnormal clinically significant in Part A of the study.
Time frame: Up to Day 26
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal- Clinically Significant Electrocardiogram (ECG) Findings- Part A | 0 Participants |
Primary
Number of Participants With Abnormal Hematology Value of PCI- Part A
Blood samples were collected fasting on Day -1, and prior to breakfast (early in the morning, fasting) on Days 2, 4, 7, 11 and on Day 15 prior to checkout (24 hours post last-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Data for only those parameters (Hematocrit, Hemoglobin and Total neutrophils) are presented for which findings are of PCI either high or low.
Time frame: Up to Day 26
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part A | Hemoglobin, high | 2 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part A | Hematocrit, high | 2 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part A | Total neutrophil, low | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part A | Hemoglobin, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part A | Hematocrit, high | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part A | Total neutrophil, low | 0 Participants |
Primary
Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm)
Blood samples were collected fasting on Day -2, and prior to breakfast (early in the morning, fasting) on Days 2 (pre-dose), 4, 7, 10, 13 and on Day 15 prior to checkout (24hrs post-dose), and at Follow-up. When this resulted in multiple samples at the same time point, only one sample was collected (example, when 24hrs post dose = pre-dose (time 0) for the next dose). Data for only those parameters (Platelet count, Total neutrophils and Lymphocytes) are presented for which findings are of PCI either high or low.
Time frame: Up to Day 26
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 1 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 1 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 1 Participants |
| GSK1292263 100 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Total neutrophils, low | 1 Participants |
| Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Lymphocytes, low | 0 Participants |
| Placebo | Number of Participants With Abnormal Hematology Value of PCI- Part B (Pooled Treatment Arm) | Platelet count, low | 0 Participants |
Primary
Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in)
Blood samples were collected on Day 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (Lymphocytes) are presented for which findings are of PCI either high or low.
Time frame: Days 14 and 28
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in) | Lymphocytes, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in) | Lymphocytes, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in) | Lymphocytes, low | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Run-in) | Lymphocytes, high | 0 Participants |
Primary
Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout)
Blood samples were collected at screening, and on Days 1 (first day of washout), 14 and 28 prior to breakfast (early in the morning, fasting). Data for only those parameters (White blood cells \[WBC\], Total neutrophils, Hematocrit and Lymphocytes) are presented for which findings are of PCI either high or low.
Time frame: Up to Day 28
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout) | WBC, low | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout) | Total neutrophil, low | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout) | WBC, high | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout) | Hematocrit, high | 2 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Abnormal Hematology Value of PCI- Part B (Washout) | Lymphocytes, low | 2 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 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, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Time frame: Up to Day 26
Population: Safety Population consisted of all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A | Any AE | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A | Any SAE | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs)- Part A | Any AE | 2 Participants |
| 800 mg GSK1292263 | 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 SAEs- Part B (Pooled Treatment Arm)
An AE is defined as any untoward medical occurrence in a 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, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Time frame: Up to Day 26
Population: All subject Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 6 Participants |
| 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 2 Participants |
| 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 3 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 3 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 4 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 6 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 4 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 5 Participants |
| GSK1292263 300 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 7 Participants |
| GSK1292263 300 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 8 Participants |
| GSK1292263 800 mg | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| Placebo | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any SAE | 0 Participants |
| Placebo | Number of Participants With Any AEs and SAEs- Part B (Pooled Treatment Arm) | Any AE | 4 Participants |
Primary
Number of Participants With Any AEs and SAEs- Part B (Run-in)
An AE is defined as any untoward medical occurrence in a 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, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Time frame: Up to Day 28
Population: All subject Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Run-in) | Any AE | 19 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Run-in) | Any SAE | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Run-in) | Any AE | 8 Participants |
| 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Run-in) | Any SAE | 0 Participants |
Primary
Number of Participants With Any AEs and SAEs- Part B (Washout)
An AE is defined as any untoward medical occurrence in a 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, or is a congenital anomaly/birth defect, or is an important medical events that jeopardize the participants or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition, or a drug-induced liver injury.
Time frame: Up to Day 28
Population: All subject Population consisted of all participants who received at least one dose of study medication.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Washout) | Any AE | 14 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Washout) | Any SAE | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Washout) | Any SAE | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Any AEs and SAEs- Part B (Washout) | Any AE | 37 Participants |
Primary
Number of Participants With Vital Signs of PCI- Part B (Washout)
Assessment of vital signs including SBP, DBP heart rate was performed at Screening, on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Time frame: Up to day 28
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of PCI- Part B (Washout) | Heart rate, high | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of PCI- Part B (Washout) | SBP, high | 4 Participants |
Primary
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm)
Assessment of vital signs including SBP, DBP and heart rate was performed after admission on Day-2, and pre-breakfast on Days -1, 4, and 10 in a fasting state early in the morning (prior to dosing), and at Follow-up. On Days 1, 7 and 14, they were also be 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. Data for only those parameters are presented for which findings are of PCI either high or low.
Time frame: Up to Day 26
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 1 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| Atorvastatin 10 mg + GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 1 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 3 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 0 Participants |
| Atorvastatin 10 mg + Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 1 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 2 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 1 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 0 Participants |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 1 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 1 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 1 Participants |
| Atorvastatin 80 mg + GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 2 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 0 Participants |
| Atorvastatin 80 mg + Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 1 Participants |
| GSK1292263 100 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| GSK1292263 100 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 1 Participants |
| GSK1292263 100 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 1 Participants |
| GSK1292263 300 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 2 Participants |
| GSK1292263 300 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| GSK1292263 300 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 0 Participants |
| GSK1292263 800 mg | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | Heart rate, high | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | SBP, high | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, high | 0 Participants |
| Placebo | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Pooled Treatment Arm) | DBP, low | 0 Participants |
Primary
Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in)
Assessment of vital signs including SBP, DBP and heart rate was performed on Days 1, 14 and 28 in the morning. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Data for only those parameters are presented for which findings are of PCI either high or low.
Time frame: Up to day 28
Population: All subjects Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in) | SBP, high | 1 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in) | SBP, low | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in) | SBP, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance- Part B (Run-in) | SBP, low | 0 Participants |
Primary
Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A
Assessment of vital signs including systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate was performed after admission on Day -1 and at Follow-up. On Days 1, 7 and 14, they were taken at pre-dose, 1, 3, 6, 8, 14 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. Data for only those parameters are presented for which findings are of PCI either high or low.
Time frame: Up to Day 26
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A | DBP, low | 0 Participants |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A | DBP, high | 0 Participants |
| 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A | DBP, high | 1 Participants |
| 800 mg GSK1292263 | Number of Participants With Vital Signs of Potential Clinical Importance (PCI)- Part A | DBP, low | 0 Participants |
Primary
Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Time frame: Baseline and Day 14
Population: All subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | 2.85 Percent change | Standard Deviation 31.217 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | -1.93 Percent change | Standard Deviation 27.152 |
| 800 mg GSK1292263 | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -17.93 Percent change | Standard Deviation 19.839 |
| 800 mg GSK1292263 | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | -8.72 Percent change | Standard Deviation 31.791 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -22.22 Percent change | Standard Deviation 20.393 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | 4.17 Percent change | Standard Deviation 38.41 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -5.03 Percent change | Standard Deviation 19.932 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | -7.19 Percent change | Standard Deviation 27.383 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -15.49 Percent change | Standard Deviation 13.681 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | -3.88 Percent change | Standard Deviation 26.818 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -27.08 Percent change | Standard Deviation 14.132 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | -1.00 Percent change | Standard Deviation 35.805 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | 4.25 Percent change | Standard Deviation 27.89 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | -5.81 Percent change | Standard Deviation 47.8 |
| GSK1292263 100 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -10.21 Percent change | Standard Deviation 22.072 |
| GSK1292263 100 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | 3.76 Percent change | Standard Deviation 41.281 |
| GSK1292263 300 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | 29.90 Percent change | Standard Deviation 99.331 |
| GSK1292263 300 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -7.62 Percent change | Standard Deviation 23.573 |
| GSK1292263 800 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | -0.15 Percent change | Standard Deviation 39.226 |
| GSK1292263 800 mg | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -10.95 Percent change | Standard Deviation 23.811 |
| Placebo | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein B100, 24 hours | -2.39 Percent change | Standard Deviation 15.932 |
| Placebo | Percent Change From Baseline for Lipid Metabolism: Apolipoprotein A1 and Apolipoprotein B100 at Day 14 | Apolipoprotein A1, 24 hours | -0.18 Percent change | Standard Deviation 49.478 |
Comparison: Atorvastatin 10 mg + GSK1292263 100 mg vs Placebo: Apolipoprotein A195% CI: [-15.7096, 26.6553]
Comparison: Atorvastatin 10 mg + GSK1292263 300 mg vs Placebo: Apolipoprotein A195% CI: [-21.784, 20.5888]
Comparison: Atorvastatin 10 mg + GSK1292263 800 mg vs Placebo: Apolipoprotein A195% CI: [-9.3489, 33.1602]
Comparison: Atorvastatin 10 mg + Ezetimibe 10 mg vs Placebo: Apolipoprotein A195% CI: [-16.9957, 24.3384]
Comparison: Atorvastatin 80 mg + GSK1292263 800 mg vs Placebo: Apolipoprotein A195% CI: [-28.2069, 37.4425]
Comparison: GSK1292263 100 mg vs Placebo: Apolipoprotein A195% CI: [-17.0405, 39.8527]
Comparison: GSK1292263 300 mg vs Placebo: Apolipoprotein A195% CI: [-21.0153, 31.5504]
Comparison: GSK1292263 800 mg vs Placebo: Apolipoprotein A195% CI: [-23.7517, 24.7608]
Comparison: Atorvastatin 10 mg + GSK1292263 100 mg vs Placebo: Apolipoprotein B10095% CI: [-3.246, 33.7161]
Comparison: Atorvastatin 10 mg + GSK1292263 300 mg vs Placebo: Apolipoprotein B10095% CI: [-21.3243, 8.9224]
Comparison: Atorvastatin 10 mg + GSK1292263 800 mg vs Placebo: Apolipoprotein B10095% CI: [-26.8137, 1.1513]
Comparison: Atorvastatin 10 mg + Ezetimibe 10 mg vs Placebo: Apolipoprotein B10095% CI: [-16.6557, 13.1191]
Comparison: Atorvastatin 80 mg + GSK1292263 800 mg vs Placebo: Apolipoprotein B10095% CI: [-45.1045, -11.3579]
Comparison: GSK1292263 100 mg vs Placebo: Apolipoprotein B10095% CI: [-23.5021, 11.3014]
Comparison: GSK1292263 300 mg vs Placebo: Apolipoprotein B10095% CI: [-25.2721, 8.2918]
Comparison: GSK1292263 800 mg vs Placebo: Apolipoprotein B10095% CI: [-26.0247, 6.6498]
Primary
Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Time frame: Baseline and Day 14
Population: All subjects Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -21.97 Perecent change | Standard Deviation 16.373 |
| 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -3.92 Perecent change | Standard Deviation 29.382 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -31.41 Perecent change | Standard Deviation 17.369 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | 34.28 Perecent change | Standard Deviation 141.042 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -12.27 Perecent change | Standard Deviation 42.191 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -13.19 Perecent change | Standard Deviation 19.202 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -13.41 Perecent change | Standard Deviation 30.613 |
| GSK1292263 100 mg | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | 1.35 Perecent change | Standard Deviation 46.155 |
| GSK1292263 300 mg | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -21.98 Perecent change | Standard Deviation 37.91 |
| GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -33.75 Perecent change | Standard Deviation 16.915 |
| Placebo | Percent Change From Baseline in Lipid Metabolism: Apolipoprotein E at Day 14 (24 Hours) | -1.58 Perecent change | Standard Deviation 36.044 |
95% CI: [-24.2901, 32.6057]
95% CI: [-40.4767, 1.906]
95% CI: [-27.2281, 15.1569]
95% CI: [-47.9323, 3.202]
95% CI: [-38.1027, 25.3126]
95% CI: [-45.5492, 1.8605]
95% CI: [-45.0846, 13.3024]
95% CI: [-48.3842, -12.5064]
Primary
Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Time frame: Baseline and Day 14
Population: All subjects Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | -5.17 Percent change | Standard Deviation 9.21 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 7.50 Percent change | Standard Deviation 13.639 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -9.53 Percent change | Standard Deviation 8.502 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | -18.67 Percent change | Standard Deviation 16.693 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -6.80 Percent change | Standard Deviation 14.522 |
| 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | -15.98 Percent change | Standard Deviation 24.307 |
| 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | -3.61 Percent change | Standard Deviation 12.355 |
| 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 14.97 Percent change | Standard Deviation 7.7 |
| 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -10.01 Percent change | Standard Deviation 21.231 |
| 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -11.67 Percent change | Standard Deviation 18.562 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -24.09 Percent change | Standard Deviation 18.017 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -26.59 Percent change | Standard Deviation 13.742 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | -32.81 Percent change | Standard Deviation 21.249 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | -10.31 Percent change | Standard Deviation 8.912 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 31.09 Percent change | Standard Deviation 11.966 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -0.37 Percent change | Standard Deviation 19.794 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | -0.03 Percent change | Standard Deviation 14.714 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | 10.70 Percent change | Standard Deviation 32.177 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | 2.08 Percent change | Standard Deviation 16.176 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | 0.89 Percent change | Standard Deviation 12.671 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | -14.23 Percent change | Standard Deviation 9.64 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | -10.44 Percent change | Standard Deviation 21.628 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 6.03 Percent change | Standard Deviation 11.85 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -24.81 Percent change | Standard Deviation 12.317 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -21.19 Percent change | Standard Deviation 11.92 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -18.63 Percent change | Standard Deviation 16.534 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 26.22 Percent change | Standard Deviation 15.84 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | -5.52 Percent change | Standard Deviation 7.721 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | -21.39 Percent change | Standard Deviation 28.19 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -21.88 Percent change | Standard Deviation 11.157 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | 2.27 Percent change | Standard Deviation 17.025 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | 1.09 Percent change | Standard Deviation 6.724 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 4.50 Percent change | Standard Deviation 10.936 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -0.94 Percent change | Standard Deviation 8.977 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | 15.01 Percent change | Standard Deviation 59.194 |
| GSK1292263 100 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | -3.95 Percent change | Standard Deviation 23.855 |
| GSK1292263 100 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -10.24 Percent change | Standard Deviation 11.438 |
| GSK1292263 100 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | -5.81 Percent change | Standard Deviation 10.091 |
| GSK1292263 100 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -9.32 Percent change | Standard Deviation 13.107 |
| GSK1292263 100 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 9.17 Percent change | Standard Deviation 10.277 |
| GSK1292263 300 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | -30.84 Percent change | Standard Deviation 11.753 |
| GSK1292263 300 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | -12.06 Percent change | Standard Deviation 9.65 |
| GSK1292263 300 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -11.86 Percent change | Standard Deviation 16.873 |
| GSK1292263 300 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 9.76 Percent change | Standard Deviation 17.16 |
| GSK1292263 300 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -17.02 Percent change | Standard Deviation 12.376 |
| GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | 18.95 Percent change | Standard Deviation 12.847 |
| GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | -34.66 Percent change | Standard Deviation 21.197 |
| GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | -19.94 Percent change | Standard Deviation 10.688 |
| GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | -14.05 Percent change | Standard Deviation 7.614 |
| GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | -22.62 Percent change | Standard Deviation 10.29 |
| Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | HDLc | -1.37 Percent change | Standard Deviation 7.14 |
| Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Triglyceides | 18.90 Percent change | Standard Deviation 18.225 |
| Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | LDLc | 0.77 Percent change | Standard Deviation 11.347 |
| Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Non-HDLc | 3.17 Percent change | Standard Deviation 9.283 |
| Placebo | Percent Change From Baseline in Lipid Metabolism: High Density Lipids Cholesterol (HDLc), Low Density Lipids Cholesterol (LDLc), Tryglycerides, Non-HDLc and Total Cholesterol at Day 14 (24 Hours) | Total cholesterol | 2.18 Percent change | Standard Deviation 7.9 |
Comparison: For HDLc95% CI: [-4.5469, 14.7495]
Comparison: Fo HDLc95% CI: [2.5937, 21.9532]
Comparison: For HDLc95% CI: [18.955, 38.7102]
Comparison: For HDLc95% CI: [-5.5562, 12.9578]
Comparison: For HDLc95% CI: [8.612, 33.281]
Comparison: For HDLc95% CI: [-0.9675, 22.0898]
Comparison: For HDLc95% CI: [-0.2902, 22.5351]
Comparison: For HDLc95% CI: [9.7527, 31.6262]
Comparison: For LDLc95% CI: [-18.775, 9.6768]
Comparison: For LDLc95% CI: [-24.4549, 3.7803]
Comparison: For LDLc95% CI: [-36.0144, -6.619]
Comparison: For LDLc95% CI: [-34.271, -6.0755]
Comparison: For LDLc95% CI: [-49.3385, -8.1558]
Comparison: For LDLc95% CI: [-23.3049, -0.9514]
Comparison: For LDLc95% CI: [-27.1364, -4.4589]
Comparison: For LDLc95% CI: [-32.3413, -11.2372]
Comparison: For Triglycerides95% CI: [-38.446, -2.4169]
Comparison: For Triglycerides95% CI: [-39.1603, -4.513]
Comparison: For Triglycerides95% CI: [-52.3394, -24.2717]
Comparison: For Triglycerides95% CI: [-33.502, 2.491]
Comparison: For Triglycerides95% CI: [-40.296, -3.2667]
Comparison: For Triglycerides95% CI: [-38.3519, -4.4911]
Comparison: For Triglycerides95% CI: [-63.465, -29.2561]
Comparison: For Triglycerides95% CI: [-70.7854, -38.9007]
Comparison: For Non-HDLc95% CI: [-21.7561, 2.2448]
Comparison: For Non-HDLc95% CI: [-25.7497, -2.2787]
Comparison: For Non-HDLc95% CI: [-39.8454, -15.5045]
Comparison: For Non-HDLc95% CI: [-32.6057, -9.269]
Comparison: For Non-HDLc95% CI: [-29.0346, -14.3696]
Comparison: For Non-HDLc95% CI: [-23.0636, -3.2961]
Comparison: For Non-HDLc95% CI: [-31.942, -12.3605]
Comparison: For Non-HDLc95% CI: [-36.2874, -17.6092]
Comparison: For Cholesterol95% CI: [-11.8484, 4.04]
Comparison: For Cholesterol95% CI: [-14.346, 1.4722]
Comparison: For Cholesterol95% CI: [-18.3923, -2.196]
Comparison: For Cholesterol95% CI: [-19.7688, -4.3609]
Comparison: For Cholesterol95% CI: [-13.9778, -1.9039]
Comparison: For Cholesterol95% CI: [-15.9023, -0.866]
Comparison: For Cholesterol95% CI: [-23.1404, -8.2592]
Comparison: For Cholesterol95% CI: [-23.8395, -9.6161]
Primary
Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours)
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was the closest scheduled value prior to dosing. 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Time frame: Baseline and Day 14
Population: All subjects Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | -12.25 Percent change | Standard Deviation 14.784 |
| 800 mg GSK1292263 | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | -21.12 Percent change | Standard Deviation 20.549 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | -41.61 Percent change | Standard Deviation 14.248 |
| Atorvastatin 10 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | 0.94 Percent change | Standard Deviation 20.727 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | -28.69 Percent change | Standard Deviation 11.963 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | -34.35 Percent change | Standard Deviation 16.047 |
| Atorvastatin 80 mg + Placebo | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | 10.84 Percent change | Standard Deviation 56.487 |
| GSK1292263 100 mg | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | -16.78 Percent change | Standard Deviation 15.615 |
| GSK1292263 300 mg | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | -17.63 Percent change | Standard Deviation 23.327 |
| GSK1292263 800 mg | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | -32.01 Percent change | Standard Deviation 11.287 |
| Placebo | Percent Change From Baseline in Lipid Metabolism: LDL/HDL Ratio at Day 14 (24 Hours) | 2.55 Percent change | Standard Deviation 12.789 |
95% CI: [-26.6276, 2.3814]
95% CI: [-35.9419, -7.3181]
95% CI: [-56.3924, -26.6205]
95% CI: [-42.2554, -13.8263]
95% CI: [-51.5654, -12.4042]
95% CI: [-34.8358, -5.2472]
95% CI: [-36.6155, -7.1913]
95% CI: [-49.722, -21.7485]
Primary
Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A
Serial blood samples for the determination of the PK for GSK1292263, on Days 1 and 14 were collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (no 48 hour sample on Day 1).
Time frame: On Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | tmax, Day 1 | 6.000 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | tmax, Day 14 | 3.000 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | t1/2, Day 1 | 11.185 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | t1/2, Day 14 | 20.629 hours |
| 800 mg GSK1292263 | Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | t1/2, Day 14 | 19.395 hours |
| 800 mg GSK1292263 | Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | tmax, Day 1 | 5.000 hours |
| 800 mg GSK1292263 | Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | t1/2, Day 1 | 16.164 hours |
| 800 mg GSK1292263 | Time of Occurrence of Cmax (Tmax) and Terminal Phase Half-life (t1/2) GSK1292263- Part A | tmax, Day 14 | 5.067 hours |
Primary
Tlag of GSK1292263- Part B (Pooled Treatment Arm)
Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose.
Population: PK parameter Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tlag of GSK1292263- Part B (Pooled Treatment Arm) | 0.000 hours |
| 800 mg GSK1292263 | Tlag of GSK1292263- Part B (Pooled Treatment Arm) | 0.000 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tlag of GSK1292263- Part B (Pooled Treatment Arm) | 0.000 hours |
| Atorvastatin 10 mg + Placebo | Tlag of GSK1292263- Part B (Pooled Treatment Arm) | 0.000 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tlag of GSK1292263- Part B (Pooled Treatment Arm) | 0.000 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tlag of GSK1292263- Part B (Pooled Treatment Arm) | 0.000 hours |
| Atorvastatin 80 mg + Placebo | Tlag of GSK1292263- Part B (Pooled Treatment Arm) | 0.000 hours |
Primary
Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of GSK1292263 were taken on Days 1 and 14. For monotherapy arms, serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1 and 14. Blood samples for PK were collected on Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hours PK sample was collected on Day 16).
Time frame: On Day 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. On Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 14 | 5.000 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 14 | 26.453 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 1 | 3.983 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 1 | 12.630 hours |
| 800 mg GSK1292263 | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 14 | 21.569 hours |
| 800 mg GSK1292263 | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 1 | 10.270 hours |
| 800 mg GSK1292263 | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 14 | 4.000 hours |
| 800 mg GSK1292263 | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 1 | 5.008 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 1 | 10.416 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 14 | 4.000 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 1 | 4.000 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 14 | 21.846 hours |
| Atorvastatin 10 mg + Placebo | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 14 | 4.000 hours |
| Atorvastatin 10 mg + Placebo | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 1 | 4.000 hours |
| Atorvastatin 10 mg + Placebo | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 14 | 24.225 hours |
| Atorvastatin 10 mg + Placebo | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 1 | 12.372 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 14 | 4.000 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 1 | 4.000 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 1 | 15.305 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 14 | 23.893 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 14 | 3.983 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 14 | 25.203 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 1 | 14.342 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 1 | 4.000 hours |
| Atorvastatin 80 mg + Placebo | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 14 | 19.478 hours |
| Atorvastatin 80 mg + Placebo | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 14 | 4.000 hours |
| Atorvastatin 80 mg + Placebo | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | tmax, Day 1 | 3.475 hours |
| Atorvastatin 80 mg + Placebo | Tmax and t1/2 of GSK1292263- Part B (Pooled Treatment Arm) | t1/2, Day 1 | 14.464 hours |
Primary
Tmax of Atorvastatin- Part A
Serial blood samples for the determination of the PK for atorvastatin on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Population: PK parameter Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin- Part A | Day -1 | 3.000 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin- Part A | Day 1 | 4.000 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin- Part A | Day 14 | 2.250 hours |
Primary
Tmax of Atorvastatin- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 2.500 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 4.000 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 4.992 hours |
| 800 mg GSK1292263 | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 4.000 hours |
| 800 mg GSK1292263 | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 3.000 hours |
| 800 mg GSK1292263 | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 6.000 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 3.500 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 3.983 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 3.000 hours |
| Atorvastatin 10 mg + Placebo | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 3.017 hours |
| Atorvastatin 10 mg + Placebo | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 3.525 hours |
| Atorvastatin 10 mg + Placebo | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 3.992 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 4.000 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 2.000 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 4.000 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 2.508 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 3.492 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 2.067 hours |
| Atorvastatin 80 mg + Placebo | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 14 | 3.000 hours |
| Atorvastatin 80 mg + Placebo | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day -1 | 1.517 hours |
| Atorvastatin 80 mg + Placebo | Tmax of Atorvastatin- Part B (Pooled Treatment Arm) | Day 1 | 2.000 hours |
Primary
Trough Concentration of Atorvastatin
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin were planned to be collected on Day -1 and for atorvastatin on Days 1 and 14. Blood samples for PK were planned to be collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were planned to be collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was planned to be collected on Day 16).
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Data was not collected for this outcome measure.
Primary
Trough Concentration of GSK1292263
Trough samples for GSK1292263 PK (all treatment arms) were planned to be collected early in the morning on Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48h PK sample was collected on Day 16). (pre-dose for Days 13 and 14; trough Day 15 = 24h post last dose; trough Day 16 = 48h post last dose).
Time frame: On Days 13, 14, 15 and 16 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK concentration Population. Data was not collected for this outcome measure.
Primary
Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14
Blood samples were collected fasting on Days 1 (pre-dose), 7 and 15 prior to checkout (24 hours post-dose), and at Follow-up. When this results in multiple samples at the same time point, only one sample will be collected (example, when 24 hours post-dose = pre-dose (time 0) for the next dose). Baseline was Day -1 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 is missing, the change from Baseline was set to missing as well. Percent change from Baseline was calculated as the change from Baseline divided by the Baseline value then multiplied by 100.
Time frame: Baseline and Day 14
Population: All subjects Population. Only those participants with data available at the indicated time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.13341 millimoles per liter | Geometric Coefficient of Variation -167.395 |
| 800 mg GSK1292263 | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.30812 millimoles per liter | Geometric Coefficient of Variation -360.966 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.12845 millimoles per liter | Geometric Coefficient of Variation -68.4294 |
| Atorvastatin 10 mg + Placebo | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.25228 millimoles per liter | Geometric Coefficient of Variation 477.038 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.09060 millimoles per liter | Geometric Coefficient of Variation -146.956 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.04974 millimoles per liter | Geometric Coefficient of Variation -76.1973 |
| Atorvastatin 80 mg + Placebo | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.20164 millimoles per liter | Geometric Coefficient of Variation -485.961 |
| GSK1292263 100 mg | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.30543 millimoles per liter | Geometric Coefficient of Variation -159.012 |
| GSK1292263 300 mg | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.37442 millimoles per liter | Geometric Coefficient of Variation -111.818 |
| GSK1292263 800 mg | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.13079 millimoles per liter | Geometric Coefficient of Variation -115.21 |
| Placebo | Weighted Mean Area Under Concentration Curve From 0 to 24 Hours (AUC [0-24]) Change From Baseline for Triglycerides at Day 14 | 0.28863 millimoles per liter | Geometric Coefficient of Variation 93.305 |
95% CI: [-1.0123, 0.1942]
95% CI: [-0.9063, 0.3141]
95% CI: [-1.4125, -0.2098]
95% CI: [-0.9831, 0.1394]
95% CI: [-0.6009, -0.1669]
95% CI: [-1.1657, -0.1302]
95% CI: [-1.2804, -0.2844]
95% CI: [-1.3652, -0.4026]
Secondary
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Population: PK parameter Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day -1 | 119.66 nanograms hour per milliliter | Geometric Coefficient of Variation 72.635 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day 1 | 127.70 nanograms hour per milliliter | Geometric Coefficient of Variation 49.098 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day 14 | 139.78 nanograms hour per milliliter | Geometric Coefficient of Variation 47.491 |
Secondary
AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 10.07 nanograms hour per milliliter | Geometric Coefficient of Variation 12.346 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 16.72 nanograms hour per milliliter | Geometric Coefficient of Variation 19.509 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 16.02 nanograms hour per milliliter | Geometric Coefficient of Variation 9.355 |
| 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 18.28 nanograms hour per milliliter | Geometric Coefficient of Variation 40.611 |
| 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 20.25 nanograms hour per milliliter | Geometric Coefficient of Variation 47.047 |
| 800 mg GSK1292263 | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 16.54 nanograms hour per milliliter | Geometric Coefficient of Variation 37.123 |
| Atorvastatin 10 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 14.37 nanograms hour per milliliter | Geometric Coefficient of Variation 48.598 |
| Atorvastatin 10 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 14.89 nanograms hour per milliliter | Geometric Coefficient of Variation 33.541 |
| Atorvastatin 10 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 13.82 nanograms hour per milliliter | Geometric Coefficient of Variation 43.131 |
| Atorvastatin 10 mg + Placebo | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 12.38 nanograms hour per milliliter | Geometric Coefficient of Variation 74.286 |
| Atorvastatin 10 mg + Placebo | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 13.60 nanograms hour per milliliter | Geometric Coefficient of Variation 78.379 |
| Atorvastatin 10 mg + Placebo | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 12.03 nanograms hour per milliliter | Geometric Coefficient of Variation 63.145 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 18.18 nanograms hour per milliliter | Geometric Coefficient of Variation 36.758 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 15.10 nanograms hour per milliliter | Geometric Coefficient of Variation 26.181 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 12.41 nanograms hour per milliliter | Geometric Coefficient of Variation 53.128 |
| Atorvastatin 80 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 146.23 nanograms hour per milliliter | Geometric Coefficient of Variation 55.353 |
| Atorvastatin 80 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 144.23 nanograms hour per milliliter | Geometric Coefficient of Variation 58.954 |
| Atorvastatin 80 mg + GSK1292263 800 mg | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 163.16 nanograms hour per milliliter | Geometric Coefficient of Variation 73.666 |
| Atorvastatin 80 mg + Placebo | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 156.41 nanograms hour per milliliter | Geometric Coefficient of Variation 42.286 |
| Atorvastatin 80 mg + Placebo | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 133.96 nanograms hour per milliliter | Geometric Coefficient of Variation 36.159 |
| Atorvastatin 80 mg + Placebo | AUC (0-24) of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 150.41 nanograms hour per milliliter | Geometric Coefficient of Variation 37.44 |
Secondary
Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Population: PK parameter Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day -1 | 17.521 nanograms per milliliter | Geometric Coefficient of Variation 66.1066 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day 1 | 15.535 nanograms per milliliter | Geometric Coefficient of Variation 48.2576 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day 14 | 21.271 nanograms per milliliter | Geometric Coefficient of Variation 30.4382 |
Secondary
Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 1.073 nanograms per milliliter | Geometric Coefficient of Variation 19.3329 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 0.634 nanograms per milliliter | Geometric Coefficient of Variation 12.5545 |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 1.298 nanograms per milliliter | Geometric Coefficient of Variation 37.3615 |
| 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 1.152 nanograms per milliliter | Geometric Coefficient of Variation 53.4256 |
| 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 1.217 nanograms per milliliter | Geometric Coefficient of Variation 36.0597 |
| 800 mg GSK1292263 | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 1.388 nanograms per milliliter | Geometric Coefficient of Variation 42.8163 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 0.947 nanograms per milliliter | Geometric Coefficient of Variation 39.3947 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 1.084 nanograms per milliliter | Geometric Coefficient of Variation 49.9097 |
| Atorvastatin 10 mg + GSK1292263 800 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 1.048 nanograms per milliliter | Geometric Coefficient of Variation 33.9165 |
| Atorvastatin 10 mg + Placebo | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 0.869 nanograms per milliliter | Geometric Coefficient of Variation 62.0112 |
| Atorvastatin 10 mg + Placebo | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 0.952 nanograms per milliliter | Geometric Coefficient of Variation 63.1814 |
| Atorvastatin 10 mg + Placebo | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 1.028 nanograms per milliliter | Geometric Coefficient of Variation 67.063 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 1.349 nanograms per milliliter | Geometric Coefficient of Variation 42.0203 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 1.185 nanograms per milliliter | Geometric Coefficient of Variation 119.9675 |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 1.234 nanograms per milliliter | Geometric Coefficient of Variation 44.7679 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 19.991 nanograms per milliliter | Geometric Coefficient of Variation 71.2442 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 26.106 nanograms per milliliter | Geometric Coefficient of Variation 102.2617 |
| Atorvastatin 80 mg + GSK1292263 800 mg | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 22.645 nanograms per milliliter | Geometric Coefficient of Variation 75.7161 |
| Atorvastatin 80 mg + Placebo | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 26.400 nanograms per milliliter | Geometric Coefficient of Variation 44.9589 |
| Atorvastatin 80 mg + Placebo | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 21.149 nanograms per milliliter | Geometric Coefficient of Variation 39.5618 |
| Atorvastatin 80 mg + Placebo | Cmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 27.236 nanograms per milliliter | Geometric Coefficient of Variation 68.7891 |
Secondary
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A
Serial blood samples for the determination of the PK for atorvastatin metabolites on Day -1 was collected at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose (24 hour sample Day -1 = 0 hour sample Day 1). Serial blood samples for the determination of the PK for atorvastatin metabolites on Days 1 and 14 will be collected at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose (no 48h sample on Day 1).
Time frame: On Day -1 at immediately pre-morning dose=pre-breakfast (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-morning dose. on Days 1 and 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hour post-morning dose.
Population: PK parameter Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day 1 | 4.000 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day 14 | 2.500 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part A | Day -1 | 3.000 hours |
Secondary
Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16).
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose and on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose
Population: PK parameter Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 6.000 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 4.500 hours |
| 80 mg Atorvastatin + 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 6.000 hours |
| 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 6.000 hours |
| 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 4.000 hours |
| 800 mg GSK1292263 | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 4.000 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 4.000 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 4.025 hours |
| Atorvastatin 10 mg + GSK1292263 800 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 5.000 hours |
| Atorvastatin 10 mg + Placebo | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 4.000 hours |
| Atorvastatin 10 mg + Placebo | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 4.000 hours |
| Atorvastatin 10 mg + Placebo | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 5.000 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 4.000 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 4.000 hours |
| Atorvastatin 10 mg + Ezetimibe 10 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 6.000 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 4.000 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 4.000 hours |
| Atorvastatin 80 mg + GSK1292263 800 mg | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 3.992 hours |
| Atorvastatin 80 mg + Placebo | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 14 | 3.983 hours |
| Atorvastatin 80 mg + Placebo | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day -1 | 3.000 hours |
| Atorvastatin 80 mg + Placebo | Tmax of Atorvastatin Metabolite (2-Hydroxyatorvastatin)- Part B (Pooled Treatment Arm) | Day 1 | 3.000 hours |
Secondary
Trough Concentration of Atorvastatin Metabolite (2-Hydroxyatorvastatin)
For co-dosing arms, serial blood samples for the determination of the PK of atorvastatin metabolites were supposed to collected on Day -1 and for atorvastatin metabolites on Days 1 and 14. Blood samples for PK were supposed to collected on Days -1 (co-dosing arms only) and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. Blood samples for PK were supposed to collected on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose (48 hour PK sample was collected on Day 16). However no data was collected.
Time frame: On Days -1 and 1 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, and 24 hours post-morning dose. on Day 14 at immediately pre-morning dose (time 0), 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14, 24 and 48 hours post-morning dose