Diabetes Mellitus, Type 2
Conditions
Keywords
Tolerability, Pharmacokinetics, Safety, Pharmacodynamics, Glucose
Brief summary
The purpose of this study is to see if GSK1292263 is safe and well-tolerated when administered to type 2 diabetics, and to get preliminary information about whether it may be effective in the treatment of type 2 diabetes.
Detailed description
Data from this study will be used to assess the potential of GSK1292263 as a treatment for T2DM, and will aid the design and dose selection of future studies of longer duration in T2DM subjects that will evaluate GSK1292263 alone or in combination with other anti-diabetic drugs.
Interventions
DRUGGSK1292263
GSK1292263 is an immediate-release round, white, film-coated tablet provided in 3 strengths, 25mg, 75mg and 200mg being developed for the treatment of type 2 diabetes.
Matching placebo to active drug GSK1292263
DRUGSitagliptin
Sitagliptin (Januvia) 100mg tablets are beige, round, film-coated tablets with 277 on one side.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* Male or female subjects, 18 - 60 years of age, inclusive, at the time of signing the 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. FSH and estradiol levels will be checked at Screening for postmenopausal women. Simultaneous follicle stimulating hormone (FSH) \> 40 MlU/ml and estradiol \< 40pg/ml (\<140pmol/L) is confirmatory. * Except as noted elsewhere, subjects should have no significant known medical conditions other than T2DM, as determined by a responsible physician, based on a medical evaluation including medical history, physical examination, laboratory tests and ECGs. A subject with a clinical abnormality or laboratory parameters that meets
Exclusion criteria
but is outside the reference range for the population being studied may be included only if the Investigator and the GSK Medical Monitor agree that the finding is unlikely to introduce additional risk factors and will not interfere with the study procedures. * BMI (body mass index) within the range 22-35 kg/m2, inclusive. * Part A - T2DM diagnosed by American Diabetes Association criteria at least 3 months prior to Screening with: * Currently controlled by diet and exercise. * Fasting plasma glucose (FPG) level \<= 250mg/dL at the Screening visit * FPG level \<= 250mg/dL on Day -1 * HbA1c between 6.5 and 11%, inclusive, at Screening visit * For Parts B and C, T2DM diagnosed by American Diabetes Association criteria at least 3 months prior to Screening with: * T2DM currently controlled by diet and exercise, or, if on medication, subjects must be treating their T2DM using one of the following regimens: * Metformin as monotherapy * Sulfonylurea as monotherapy * Metformin and sulfonylurea in combination, if both components are being administered at doses that are half their maximum dose or less * DPP-IV inhibitors, either as monotherapy or in combination with other agent(s) on this list at half maximal dose or less * Exenatide, either as monotherapy or in combination with other agent(s) on this list at half maximal dose or less * For subjects that are being screened for Parts B and C, all doses of anti-diabetic medication must have been stable for at least 3 months prior to Screening, and the subject must be willing to wash out from their anti-diabetic medications from Day -7 through post-last-dose of Period 2 (Part B) or Day -7 through Day 15 (Part C). * Fasting plasma glucose (FPG) level \<= 220mg/dL at the Screening visit * FPG level \<= 250mg/dL on Day -1 * HbA1c between 7 and 11%, inclusive, at Screening visit * Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part C: Summary of Change From Baseline in Fasted Insulin | Baseline (Day 1 pre-dose) and Day -1, 13 and 14 | Blood samples were collected fasting pre-breakfast and pre-morning dose (PD time 0) on Days -1, 13 and 14 and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (4 hour post-morning dose) samples were collected just before the meal and after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value minus post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part C: Summary of Time Invariance Ratio (Rs) of Cmax | Days 1, 7, 13 and 14 | The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. Cmax for one participant from 50 BID x 14 day was not analyzed due to positive definite G Matrix. |
| Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 1 of each treatment period | Blood samples for the determination of insulin were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The unit of measure is mL/min×1/micro international unit×10\^4 (mL/min×1/µIU×10\^4). |
| Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day -1, 13 and 14 | Blood samples for the determination of insulin were collected fasting pre-breakfast and then pre-morning dose (PD time 0) on Days -1, 13 and 14, and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (approximately 4 hour post-morning dose) samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected (example: 24 hours post first-dose = pre-dose \[time 0\] for the second dose). |
| Part A: Summary of Change From Baseline in Fasted Glucose | Baseline (Day 1 pre-dose) and Day 1 (24 hours) | Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value from post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | Up to Day 1 (24 hours) | Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Up to Day 1 (24 hours) | Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | Up to Day 1 (24 hours) | Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Up to Day 1 (24 hours) | Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Summary of the OGTT Derived Parameters: Disposition Index | Up to Day 1 (24 hours) | Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated by multiplying insulin glucose index with insulin sensitivity index. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | Up to Day 1 (24 hours) | Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as insulin/glucose ratio was calculated as insulin AUC(0-3\]/glucose AUC(0-3) during OGTT, while glucose/insulin ratio was calculated as glucose AUC(0-3)/insulin AUC(0-3) during OGTT. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index | Up to Day 1 (24 hours) | Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as insulin (30 min) - insulin (0 min)/glucose (30 min) - glucose (0 min). It was calculated as insulin (30 min) - insulin (0 min)/glucose (30 min) - glucose (0 min). The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Summary of the OGTT Derived Parameters: Insulin Sensitivity Index | Up to Day 1 (24 hours) | Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as 10,000/square root (\[mean plasma insulin × mean plasma glucose during OGTT or meal challenge\] × \[fasting plasma glucose × fasting plasma insulin\]). The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part C: Summary of Change From Baseline in Fasted Glucose | Baseline (Day 1 pre-dose) and Day -1, 13 and 14. | Blood samples were collected fasting pre-breakfast and pre-morning dose (PD time 0) on Days -1, 13 and 14 and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (4 hour post-morning dose) samples were collected just before the meal and after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value minus post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo. |
| Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Up to Week 10 | An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. |
| Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI) | Up to Week 10 | Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell count (WBC; absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit, reticulocytes and basophils. It was assessed on Screening, Day -1, Day 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters (hemoglobin, high) for which at least one value of PCI was reported are summarized. Null data is not presented. |
| Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Up to Week 10 | Clinical chemistry parameters included blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), total and direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, glucose fasting, gamma glutamyltransferase (GGT), albumin, sodium, magnesium, phosphorus inorganic, calcium, total carbon dioxide (CO2), alkaline phosphatase (ALP), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, free fatty acid (non-esterified fatty acids; \[NEFA\]), high-density lipoprotein (HDL) cholesterol and total protein. It was assessed on Screening, Day -1, Day 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented. |
| Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings | Up to Week 10 | Twelve-lead ECGs was obtained in a supine position at each time point during the study using an ECG machine that automatically measured PR, QRS, QT and QTc intervals (QT duration corrected for heart rate by Bazett's formula \[QTcB\] and Fridericia's formula \[QTcF\]). Participants with abnormal clinically significant ECG findings is presented. It was assessed on Screening, Day 1 at pre-dose, 1, 2, 3, 4, 6, 10, 16, 24 hours and Follow-up (7 to 10 days after final discharge). |
| Part A: Number of Participants With Abnormal Vital Signs of PCI | Up to Week 10. | Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate measurements were recorded at each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Participants with abnormal clinically significant vital signs findings is presented. It was assessed on Screening, Day -1, 1, 2 (pre-dose, 1, 3, 4, 6, 10, 16 and 24 hours of each treatment period) and Follow-up (7 to10 days after final discharge). |
| Part A: Summary of Maximum Plasma Concentration (Cmax) | Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours on Day 1 of each treatment period | The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. Blood samples for the determination of PKs was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours. |
| Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag) | Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours on Day 1 of each treatment period | The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. Blood samples for the determination of PK was collected on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours. |
| Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) | Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours on Day 1 of each treatment period | The AUC 0-24 and AUC 0-t determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours. |
| Part C: Number of Participants With AEs and SAEs | Up to Week 7 | An AE was defined as any untoward MO in a participant temporally associated with the use of a MP, whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. |
| Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Up to Week 7 | Hematology parameters included platelet count, RBC count, MCV, total neutrophils, WBC absolute, MCH, lymphocytes, MCHC, monocytes, hemoglobin, eosinophils, hematocrit, reticulocytes and basophils. It was assessed on Screening, Day -2 (can be non-fasting) and prior to breakfast (early in the morning, fasting) on Days 1, 7 and 14, and on Day 15 prior to checkout, (=24 hours post-dose) of each treatment period and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented. |
| Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Up to Week 7 | Clinical chemistry parameters included BUN, potassium, AST, total and direct bilirubin, creatinine, chloride, ALT, uric acid, glucose fasting, GGT, albumin, sodium, magnesium, phosphorus inorganic, calcium, total CO2, ALP, triglycerides, total cholesterol, LDL cholesterol, free fatty acid (NEFA), HDL cholesterol and total protein. It was assessed on Screening, Day -2 (can be non-fasting) and prior to breakfast (early in the morning, fasting) on Days 1, 7 and 14, and on Day 15 prior to checkout, (=24 hours post-dose) of each treatment period and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented. |
| Part C: Number of Participants With Significant ECG Abnormalities | Up to Week 7 | Twelve-lead ECGs was obtained in a supine position at each time point during the study using an ECG machine that automatically measured PR, QRS, QT and QTc intervals (QTcB and QTcF). Participants with abnormal clinically significant ECG findings is presented. It was assessed on Screening, on Day -1, 1, 7, 13 and 14 pre-breakfast dose (fasting) and at 1, 3, 6, 9, 12 and 24 hours of each treatment period and Follow-up (7 to 10 days after final discharge). |
| Part C: Number of Participants With Abnormal Vital Signs of PCI | Up to Week 7 | SBP, DBP and pulse rate measurements were recorded at each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Participants with abnormal clinically significant vital signs findings is presented. It was assessed on Screening, on Days -1 to 14 in a fasting state early in the morning (prior to morning dosing on days 1-14) and at Follow-up. On Days 1, 7, 13 and 14, it was also taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose each treatment period and Follow-up (7 to 10 days after final discharge). |
| Part C: Summary of Plasma Cmax | Days 1, 7, 13 and 14 | The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. |
| Part C: Summary of T-max and T-lag | Days 1, 7, 13 and 14 | The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. |
| Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | Days 1, 7, 13 and 14 | The AUC0-10, AUC0-12 and AUC0-24 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For QD and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post- breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. |
| Part C: Summary of Accumulation Ratio (Ro) | Days 1, 7, 13 and 14 | Ro was derived as follows: Ro = Day 13 (AUC0-24)/Day 1 (AUC0-24) for once daily dosing; Ro = Day 13 AM (AUC0-10)/Day 1 AM (AUC0-10) for BID dosing and Ro = Day 13 (AUC0-24)/Day 1 (AUC0-24) for BID dosing. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. Data presented for Day 13 and Day 14. |
| Part C: Summary of Time Invariance Ratio (Rs) of AUC0-10 for BID Dose of GSK1292263 | Days 1, 7, 13 and 14 | The AUC0-10 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. |
| Part C: Summary of Time Invariance Ratio (Rs) of AUC0-24 for Once Daily Dose of GSK1292263 | Days 1, 7, 13 and 14 | The AUC0-24 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part B: Number of Participants With Abnormal Hematology Parameters of PCI | Up to Week 7 | Hematology parameters included platelet count, RBC count, MCV, total neutrophils, WBC absolute, MCH, lymphocytes, MCHC, monocytes, hemoglobin, eosinophils, hematocrit, reticulocytes and basophils. It was assessed on Screening, Day -1, 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented. |
| Part B: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Up to Week 7 | Clinical chemistry parameters included BUN, potassium, AST, total and direct bilirubin, creatinine, chloride, ALT, uric acid, glucose fasting, GGT, albumin, sodium, magnesium, phosphorus inorganic, calcium, total CO2, ALP, triglycerides, total cholesterol, LDL cholesterol, free fatty acid (NEFA), HDL cholesterol and total protein. It was assessed on Screening, Day -1, 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters (Glucose, High) for which at least one value of PCI was reported are summarized. Null data is not presented. |
| Part B: Number of Participants With Significant ECG Abnormalities | Up to Week 7 | Twelve-lead ECGs was obtained in a supine position at each time point during the study using an ECG machine that automatically measured PR, QRS, QT and QTc intervals (QTcB and QTcF). Participants with abnormal clinically significant ECG findings is presented. It was assessed on Screening, Day 1 at pre-dose, 1, 2, 3, 4, 6, 10, 16, 24 hours and Follow-up (7 -10 days after final discharge). |
| Part B: Number of Participants With Abnormal Vital Signs of PCI | Up to Week 7 | SBP, DBP and pulse rate measurements were recorded at each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 min. Participants with abnormal clinically significant vital signs findings is presented. It was assessed on Screening, Day -1, 1, 2 (pre-dose, 1, 3, 4, 6, 10, 16 and 24 hours of each treatment period) and Follow-up (7 -10 days after final discharge). |
| Part B: Summary of Plasma Cmax | Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours on Day 1 of each treatment period. | The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours. |
| Part B: Summary of T-max and T-lag | Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours on Day 1 of each treatment period | The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours. |
| Part B: Summary of AUC0-t and AUC0-24 | Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours on Day 1 of each treatment period | The AUC 0-24 and AUC 0-t determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours. |
| Part B: Summary of Change From Baseline in Fasted Glucose | Baseline (Day 1 pre-dose) and Day 1 (24 hours) | Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value from post-Baseline value. |
| Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | Baseline (Day 1 pre-dose) and Day 1 (24 hours) | Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period. For breakfast, lunch and evening meal in Part B, samples were collected just after the meal and at the following times after starting each meal: 0.5, 1 and 2 hours. Samples were also collected in Part B at 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value from post-Baseline value. |
| Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered | Days 1, 7, 13 and 14 | The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (= immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. |
| Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | Days 1, 7, 13 and 14 | The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (= immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. |
| Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | Days 1, 7, 13 and 14 | The AUC0-10, AUC0-12 and AUC0-24 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post- breakfast), 1, 2, 4 (= pre lunch), 6, 10 (= immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. |
| Part B: Number of Participants With AEs and SAEs | Up to Week 7 | An AE was defined as any untoward MO in a participant temporally associated with the use of a MP, whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition. |
Countries
United States
Participant flow
Recruitment details
A total of 13, 4 and 83 participants with type 2 diabetes mellitus (T2DM) were randomized in Part A, B and C, respectively. The study was conducted from 05 June 2009 to 19 March 2010 at 8 centers in the United States.
Pre-assignment details
The maximum time a participant spent in Part A, B and C of the study was approximately 10, 7 and 7 weeks, respectively including the 28-days period allotted for screening assessments in all parts.
Participants by arm
| Arm | Count |
|---|---|
| Part A In this part (Cohort 1), drug naïve T2DM participants were randomized to receive escalating doses of GSK1292263 25 mg, 150 mg and 800 mg in each of 3 periods along with placebo and sitagliptin 100 mg orally in the other 2 periods in fasted condition. These doses were administered to the participants in an ascending sequence irrespective of the randomization order for placebo and sitagliptin. In Part A, study drug was administered 2 hours before the OGTT. | 13 |
| Part B In this part (Cohort 2), eligible T2DM participants on mono-therapy or sub-maximal anti-diabetic medications washed off these medications for 1 week and received a single dose of GSK1292263 800 mg orally in fasted or fed condition. Before participants in Part B were dosed, the safety and tolerability of GSK1292263 800 mg administered in the fasted state to 9 participants in Part A was reviewed to ensure that it was safe to proceed. In Part B, study drug was administered 30 minutes (min) after breakfast and lunch and dinner was approximately 4 and 10 hours after dosing. | 4 |
| Part C Participants were randomized to 14 days of dosing with 4 dose regimens of GSK1292263 (final doses were: 50 mg BID, 150 mg BID, 300 mg BID, and 600 mg once daily) or matching placebo (administered BID) or open-label sitagliptin 100 mg (dosed once daily with the morning dose of GSK1292263). In this part (Cohort 3 and Cohort 4), if Cohort 3 was dosed once daily, participants in Cohort 4 were enrolled to investigate the safety, tolerability, PK and PD of GSK1292263 when dosed in a BID regimen and vice versa. | 83 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 6 |
| Overall Study | Physician Decision | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Part A | Part B | Part C | Total |
|---|---|---|---|---|
| Age, Customized 18-60 Years | 13 Participants | 4 Participants | 83 Participants | 100 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 12 Participants | 3 Participants | 75 Participants | 90 Participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 22 Participants | 27 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 61 Participants | 73 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 13 | 0 / 4 | 0 / 4 | 0 / 14 | 0 / 16 | 0 / 12 | 0 / 14 | 0 / 15 | 0 / 12 |
| other Total, other adverse events | 2 / 11 | 2 / 12 | 2 / 12 | 4 / 11 | 2 / 13 | 0 / 4 | 1 / 4 | 4 / 14 | 5 / 16 | 1 / 12 | 4 / 14 | 4 / 15 | 2 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 | 0 / 12 | 0 / 11 | 0 / 13 | 0 / 4 | 0 / 4 | 0 / 14 | 0 / 16 | 0 / 12 | 0 / 14 | 0 / 15 | 0 / 12 |
Outcome results
Primary
Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI
Clinical chemistry parameters included blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), total and direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, glucose fasting, gamma glutamyltransferase (GGT), albumin, sodium, magnesium, phosphorus inorganic, calcium, total carbon dioxide (CO2), alkaline phosphatase (ALP), triglycerides, total cholesterol, low-density lipoprotein (LDL) cholesterol, free fatty acid (non-esterified fatty acids; \[NEFA\]), high-density lipoprotein (HDL) cholesterol and total protein. It was assessed on Screening, Day -1, Day 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented.
Time frame: Up to Week 10
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 0 Participants |
| Part A: Placebo | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Magnesium, High | 0 Participants |
| Part A: Placebo | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part A: GSK1292263 25 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 1 Participants |
| Part A: GSK1292263 25 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 1 Participants |
| Part A: GSK1292263 25 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Magnesium, High | 0 Participants |
| Part A: GSK1292263 150 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 0 Participants |
| Part A: GSK1292263 150 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Magnesium, High | 0 Participants |
| Part A: GSK1292263 800 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 0 Participants |
| Part A: GSK1292263 800 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Magnesium, High | 0 Participants |
| Part A: GSK1292263 800 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part A: Sitagliptin 100 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part A: Sitagliptin 100 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 0 Participants |
| Part A: Sitagliptin 100 mg | Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Magnesium, High | 1 Participants |
Primary
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Twelve-lead ECGs was obtained in a supine position at each time point during the study using an ECG machine that automatically measured PR, QRS, QT and QTc intervals (QT duration corrected for heart rate by Bazett's formula \[QTcB\] and Fridericia's formula \[QTcF\]). Participants with abnormal clinically significant ECG findings is presented. It was assessed on Screening, Day 1 at pre-dose, 1, 2, 3, 4, 6, 10, 16, 24 hours and Follow-up (7 to 10 days after final discharge).
Time frame: Up to Week 10
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 Participants |
| Part A: GSK1292263 25 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 Participants |
| Part A: GSK1292263 150 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 Participants |
| Part A: GSK1292263 800 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 Participants |
| Part A: Sitagliptin 100 mg | Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings | 0 Participants |
Primary
Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI)
Hematology parameters included platelet count, red blood cell (RBC) count, mean corpuscular volume (MCV), total neutrophils, white blood cell count (WBC; absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit, reticulocytes and basophils. It was assessed on Screening, Day -1, Day 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters (hemoglobin, high) for which at least one value of PCI was reported are summarized. Null data is not presented.
Time frame: Up to Week 10
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI) | 0 Participants |
| Part A: GSK1292263 25 mg | Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI) | 0 Participants |
| Part A: GSK1292263 150 mg | Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI) | 1 Participants |
| Part A: GSK1292263 800 mg | Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI) | 0 Participants |
| Part A: Sitagliptin 100 mg | Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI) | 1 Participants |
Primary
Part A: Number of Participants With Abnormal Vital Signs of PCI
Systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate measurements were recorded at each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Participants with abnormal clinically significant vital signs findings is presented. It was assessed on Screening, Day -1, 1, 2 (pre-dose, 1, 3, 4, 6, 10, 16 and 24 hours of each treatment period) and Follow-up (7 to10 days after final discharge).
Time frame: Up to Week 10.
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Abnormal Vital Signs of PCI | 0 Participants |
| Part A: GSK1292263 25 mg | Part A: Number of Participants With Abnormal Vital Signs of PCI | 0 Participants |
| Part A: GSK1292263 150 mg | Part A: Number of Participants With Abnormal Vital Signs of PCI | 0 Participants |
| Part A: GSK1292263 800 mg | Part A: Number of Participants With Abnormal Vital Signs of PCI | 0 Participants |
| Part A: Sitagliptin 100 mg | Part A: Number of Participants With Abnormal Vital Signs of PCI | 0 Participants |
Primary
Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Time frame: Up to Week 10
Population: Safety Population comprised of all participants enrolled in the study and who had received at least one dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 2 Participants |
| Part A: Placebo | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part A: GSK1292263 25 mg | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 2 Participants |
| Part A: GSK1292263 25 mg | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part A: GSK1292263 150 mg | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 2 Participants |
| Part A: GSK1292263 150 mg | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part A: GSK1292263 800 mg | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
| Part A: GSK1292263 800 mg | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 4 Participants |
| Part A: Sitagliptin 100 mg | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any AE | 2 Participants |
| Part A: Sitagliptin 100 mg | Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any SAE | 0 Participants |
Primary
Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity
Blood samples for the determination of insulin were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The unit of measure is mL/min×1/micro international unit×10\^4 (mL/min×1/µIU×10\^4).
Time frame: Day 1 of each treatment period
Population: The PK/PD Population included all participants who were in both the PK and PD populations, as well as those in the PD population who received the placebo treatment.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | 1.4 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 98 |
| Part A: GSK1292263 25 mg | Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | 2.1 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 67 |
| Part A: GSK1292263 150 mg | Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | 2.3 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 51 |
| Part A: GSK1292263 800 mg | Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | 2.8 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 86 |
| Part A: Sitagliptin 100 mg | Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | 2.7 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 86 |
Primary
Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24)
The AUC 0-24 and AUC 0-t determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours.
Time frame: Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours on Day 1 of each treatment period
Population: Pharmacokinetic Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) | AUC 0-24 | 524.30 Nanograms×hour per milliliters | Geometric Coefficient of Variation 21.138 |
| Part A: Placebo | Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) | AUC 0-t | 526.88 Nanograms×hour per milliliters | Geometric Coefficient of Variation 20.208 |
| Part A: GSK1292263 25 mg | Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) | AUC 0-24 | 1684.86 Nanograms×hour per milliliters | Geometric Coefficient of Variation 31.009 |
| Part A: GSK1292263 25 mg | Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) | AUC 0-t | 1685.44 Nanograms×hour per milliliters | Geometric Coefficient of Variation 31.015 |
| Part A: GSK1292263 150 mg | Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) | AUC 0-24 | 3985.72 Nanograms×hour per milliliters | Geometric Coefficient of Variation 28.449 |
| Part A: GSK1292263 150 mg | Part A: Summary of Area Under the Concentration-time Curve From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC0-t) and Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours (AUC0-24) | AUC 0-t | 3979.35 Nanograms×hour per milliliters | Geometric Coefficient of Variation 27.457 |
90% CI: [0.5282, 0.6375]
90% CI: [0.5325, 0.6291]
Primary
Part A: Summary of Change From Baseline in Fasted Glucose
Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value from post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Baseline (Day 1 pre-dose) and Day 1 (24 hours)
Population: The PD Population included participants from the Safety Population who had any PD parameter estimates from any portion of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Summary of Change From Baseline in Fasted Glucose | 0.52 Millimoles per Liter | Geometric Coefficient of Variation 795.822 |
| Part A: GSK1292263 25 mg | Part A: Summary of Change From Baseline in Fasted Glucose | 1.49 Millimoles per Liter | Geometric Coefficient of Variation 848.906 |
| Part A: GSK1292263 150 mg | Part A: Summary of Change From Baseline in Fasted Glucose | 0.53 Millimoles per Liter | Geometric Coefficient of Variation 533.024 |
| Part A: GSK1292263 800 mg | Part A: Summary of Change From Baseline in Fasted Glucose | 0.87 Millimoles per Liter | Geometric Coefficient of Variation 653.005 |
| Part A: Sitagliptin 100 mg | Part A: Summary of Change From Baseline in Fasted Glucose | 0.58 Millimoles per Liter | Geometric Coefficient of Variation -220.27 |
95% CI: [-1.17, 1.1]
95% CI: [-0.9, 1.35]
95% CI: [-1.1, 1.19]
95% CI: [-1.8, 0.45]
Primary
Part A: Summary of Maximum Plasma Concentration (Cmax)
The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. Blood samples for the determination of PKs was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours.
Time frame: Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours on Day 1 of each treatment period
Population: The Pharmacokinetic Population included all participants from the Safety Population who have any pharmacokinetic parameter estimates from any portion of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Summary of Maximum Plasma Concentration (Cmax) | 52.04 Nanograms per milliliters | Geometric Coefficient of Variation 17.147 |
| Part A: GSK1292263 25 mg | Part A: Summary of Maximum Plasma Concentration (Cmax) | 165.62 Nanograms per milliliters | Geometric Coefficient of Variation 37.467 |
| Part A: GSK1292263 150 mg | Part A: Summary of Maximum Plasma Concentration (Cmax) | 379.79 Nanograms per milliliters | Geometric Coefficient of Variation 28.171 |
90% CI: [0.523, 0.6335]
Primary
Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin
Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Up to Day 1 (24 hours)
Population: PD Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, iAUC 0-12 | 3.77 Pico moles per Liter | Geometric Coefficient of Variation 54.721 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, AUC 0-12 | 5.66 Pico moles per Liter | Geometric Coefficient of Variation 34.886 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, AUC 0-12 | 1533.54 Pico moles per Liter | Geometric Coefficient of Variation 32.331 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, AUC 0-12 | 23.04 Pico moles per Liter | Geometric Coefficient of Variation 30.099 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, iAUC 0-12 | 3.35 Pico moles per Liter | Geometric Coefficient of Variation 54.162 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, iAUC 0-12 | 920.62 Pico moles per Liter | Geometric Coefficient of Variation 34.611 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, AUC 0-12 | 8.11 Pico moles per Liter | Geometric Coefficient of Variation 27.492 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, iAUC 0-12 | 35.36 Pico moles per Liter | Geometric Coefficient of Variation 25.387 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, iAUC 0-12 | 10.34 Pico moles per Liter | Geometric Coefficient of Variation 45.444 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, AUC 0-12 | 2.14 Pico moles per Liter | Geometric Coefficient of Variation 1.291 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, AUC 0-12 | 39.99 Pico moles per Liter | Geometric Coefficient of Variation 23.579 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, iAUC 0-13 | 211.95 Pico moles per Liter | Geometric Coefficient of Variation 64.157 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, AUC 0-13 | 267.68 Pico moles per Liter | Geometric Coefficient of Variation 63.475 |
| Part A: Placebo | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, iAUC 0-12 | 0.05 Pico moles per Liter | Geometric Coefficient of Variation 172.301 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, AUC 0-12 | 29.72 Pico moles per Liter | Geometric Coefficient of Variation 26.567 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, iAUC 0-12 | 38.77 Pico moles per Liter | Geometric Coefficient of Variation 29.579 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, AUC 0-12 | 5.83 Pico moles per Liter | Geometric Coefficient of Variation 41.037 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, AUC 0-12 | 44.91 Pico moles per Liter | Geometric Coefficient of Variation 28.596 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, iAUC 0-13 | 199.42 Pico moles per Liter | Geometric Coefficient of Variation 46.245 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, iAUC 0-12 | 874.41 Pico moles per Liter | Geometric Coefficient of Variation 39.842 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, iAUC 0-12 | 0.06 Pico moles per Liter | Geometric Coefficient of Variation 346.41 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, iAUC 0-12 | 3.34 Pico moles per Liter | Geometric Coefficient of Variation 57.021 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, iAUC 0-12 | 2.81 Pico moles per Liter | Geometric Coefficient of Variation 194.661 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, AUC 0-12 | 1518.81 Pico moles per Liter | Geometric Coefficient of Variation 31.728 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, AUC 0-13 | 272.04 Pico moles per Liter | Geometric Coefficient of Variation 45.425 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, AUC 0-12 | 2.12 Pico moles per Liter | Geometric Coefficient of Variation 0.815 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, AUC 0-12 | 9.55 Pico moles per Liter | Geometric Coefficient of Variation 39.783 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, iAUC 0-12 | 15.04 Pico moles per Liter | Geometric Coefficient of Variation 38.723 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, AUC 0-12 | 10.62 Pico moles per Liter | Geometric Coefficient of Variation 37.541 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, iAUC 0-12 | 2.60 Pico moles per Liter | Geometric Coefficient of Variation 148.08 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, AUC 0-13 | 277.10 Pico moles per Liter | Geometric Coefficient of Variation 53.966 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, AUC 0-12 | 44.07 Pico moles per Liter | Geometric Coefficient of Variation 26.903 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, iAUC 0-12 | 38.52 Pico moles per Liter | Geometric Coefficient of Variation 28.757 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, AUC 0-12 | 2.26 Pico moles per Liter | Geometric Coefficient of Variation 10.182 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, iAUC 0-12 | 821.46 Pico moles per Liter | Geometric Coefficient of Variation 34.785 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, AUC 0-12 | 30.46 Pico moles per Liter | Geometric Coefficient of Variation 34.393 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, iAUC 0-12 | 0.12 Pico moles per Liter | Geometric Coefficient of Variation 153.295 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, AUC 0-12 | 1523.99 Pico moles per Liter | Geometric Coefficient of Variation 26.37 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, AUC 0-12 | 6.13 Pico moles per Liter | Geometric Coefficient of Variation 29.049 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, iAUC 0-12 | 3.64 Pico moles per Liter | Geometric Coefficient of Variation 42.846 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, iAUC 0-13 | 207.02 Pico moles per Liter | Geometric Coefficient of Variation 55.393 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, iAUC 0-12 | 15.56 Pico moles per Liter | Geometric Coefficient of Variation 54.028 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, iAUC 0-12 | 0.07 Pico moles per Liter | Geometric Coefficient of Variation 191.029 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, iAUC 0-12 | 846.34 Pico moles per Liter | Geometric Coefficient of Variation 29.692 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, AUC 0-12 | 51.21 Pico moles per Liter | Geometric Coefficient of Variation 26.338 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, iAUC 0-12 | 42.15 Pico moles per Liter | Geometric Coefficient of Variation 24.08 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, AUC 0-12 | 2.20 Pico moles per Liter | Geometric Coefficient of Variation 7.629 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, AUC 0-12 | 1513.90 Pico moles per Liter | Geometric Coefficient of Variation 23.322 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, AUC 0-12 | 7.44 Pico moles per Liter | Geometric Coefficient of Variation 39.162 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, iAUC 0-12 | 4.33 Pico moles per Liter | Geometric Coefficient of Variation 41.068 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, AUC 0-12 | 9.34 Pico moles per Liter | Geometric Coefficient of Variation 52.831 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, iAUC 0-12 | 1.97 Pico moles per Liter | Geometric Coefficient of Variation 83.805 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, AUC 0-13 | 280.90 Pico moles per Liter | Geometric Coefficient of Variation 46.494 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, iAUC 0-13 | 208.19 Pico moles per Liter | Geometric Coefficient of Variation 50.315 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, AUC 0-12 | 35.38 Pico moles per Liter | Geometric Coefficient of Variation 34.413 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, iAUC 0-12 | 17.74 Pico moles per Liter | Geometric Coefficient of Variation 43.836 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, iAUC 0-12 | 2.36 Pico moles per Liter | Geometric Coefficient of Variation 71.247 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, AUC 0-12 | 1418.12 Pico moles per Liter | Geometric Coefficient of Variation 31.849 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, iAUC 0-13 | 151.53 Pico moles per Liter | Geometric Coefficient of Variation 51.789 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 total, AUC 0-12 | 4.04 Pico moles per Liter | Geometric Coefficient of Variation 39.915 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, iAUC 0-12 | 3.05 Pico moles per Liter | Geometric Coefficient of Variation 50.439 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GLP-1 active, AUC 0-12 | 5.35 Pico moles per Liter | Geometric Coefficient of Variation 30.858 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, iAUC 0-12 | 3.79 Pico moles per Liter | Geometric Coefficient of Variation 105.916 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | PYY total, AUC 0-12 | 17.67 Pico moles per Liter | Geometric Coefficient of Variation 32.393 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, iAUC 0-12 | 28.03 Pico moles per Liter | Geometric Coefficient of Variation 31.909 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | GIP total, AUC 0-12 | 32.76 Pico moles per Liter | Geometric Coefficient of Variation 28.341 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | C-peptide, iAUC 0-12 | 836.98 Pico moles per Liter | Geometric Coefficient of Variation 35.373 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Insulin, AUC 0-13 | 210.66 Pico moles per Liter | Geometric Coefficient of Variation 48.374 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, iAUC 0-12 | 1.86 Pico moles per Liter | Geometric Coefficient of Variation 50.802 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-12 and iAUC 0-12 of Glucagon, Glucagon-like Peptide (GLP; Active and Total)-1, C-peptide, Total Glucose-dependent Insulinotropic Peptide (GIP) and Total Peptide Tyrosine-tyrosine (PYY) and AUC 0-13 and iAUC 0-13 of Insulin | Glucagon, AUC 0-12 | 7.44 Pico moles per Liter | Geometric Coefficient of Variation 37.297 |
95% CI: [-479.74, 379.94]
95% CI: [-507.32, 384.04]
95% CI: [-530.07, 358.37]
95% CI: [-494.09, 291.25]
95% CI: [-340.32, 261.85]
95% CI: [-429.61, 194.74]
95% CI: [-433.14, 189.18]
95% CI: [-356.07, 194.03]
95% CI: [-8.08, 13.7]
95% CI: [-8.27, 14.32]
95% CI: [0.23, 22.74]
95% CI: [-17.04, 2.86]
95% CI: [-7.28, 12.28]
95% CI: [-6.61, 13.67]
95% CI: [-2.17, 18.04]
95% CI: [-15.99, 1.88]
95% CI: [-0.79, 0.76]
95% CI: [-0.78, 0.82]
95% CI: [-0.78, 0.85]
95% CI: [2.74, 4.17]
95% CI: [-0.78, 0.75]
95% CI: [-0.79, 0.8]
95% CI: [-0.79, 0.83]
95% CI: [2.69, 4.11]
95% CI: [-2.06, 2.17]
95% CI: [-1.97, 2.42]
95% CI: [-0.35, 4.02]
95% CI: [-3.56, 0.3]
95% CI: [-1.7, 1.86]
95% CI: [-1.56, 2.13]
95% CI: [-1.08, 2.6]
95% CI: [-2.96, 0.29]
95% CI: [-4.26, 6.18]
95% CI: [-2.56, 8.69]
95% CI: [-2.98, 8.01]
95% CI: [-5.56, 4.13]
95% CI: [-6.4, 0.67]
95% CI: [-4.68, 2.95]
95% CI: [-4.16, 3.29]
95% CI: [-4.86, 1.71]
95% CI: [-168.38, 118.9]
95% CI: [-161.16, 136.7]
95% CI: [-158.07, 138.81]
95% CI: [-198.15, 64.28]
95% CI: [-150.57, 78.48]
95% CI: [-141.27, 96.22]
95% CI: [-140.36, 96.36]
95% CI: [-170.95, 38.3]
95% CI: [-2.66, 14.62]
95% CI: [-0.05, 17.86]
95% CI: [5.39, 23.24]
95% CI: [-13.33, 2.45]
95% CI: [-1.87, 11.87]
95% CI: [-0.22, 14.03]
95% CI: [1.93, 16.14]
95% CI: [-12.67, -0.11]
Primary
Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose
Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Up to Day 1 (24 hours)
Population: PD Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-13 | 9.42 Millimoles per Liter | Geometric Coefficient of Variation 16.011 |
| Part A: Placebo | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-24 | 8.72 Millimoles per Liter | Geometric Coefficient of Variation 17.563 |
| Part A: Placebo | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-13 | 2.11 Millimoles per Liter | Geometric Coefficient of Variation 32.518 |
| Part A: Placebo | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-24 | 1.18 Millimoles per Liter | Geometric Coefficient of Variation 43.037 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-24 | 9.17 Millimoles per Liter | Geometric Coefficient of Variation 22.684 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-24 | 1.04 Millimoles per Liter | Geometric Coefficient of Variation 96.395 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-13 | 9.44 Millimoles per Liter | Geometric Coefficient of Variation 24.357 |
| Part A: GSK1292263 25 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-13 | 1.35 Millimoles per Liter | Geometric Coefficient of Variation 62.815 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-13 | 1.48 Millimoles per Liter | Geometric Coefficient of Variation 59.021 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-13 | 9.15 Millimoles per Liter | Geometric Coefficient of Variation 21.389 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-24 | 1.44 Millimoles per Liter | Geometric Coefficient of Variation 137.548 |
| Part A: GSK1292263 150 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-24 | 9.03 Millimoles per Liter | Geometric Coefficient of Variation 20.928 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-13 | 8.64 Millimoles per Liter | Geometric Coefficient of Variation 20.241 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-13 | 1.78 Millimoles per Liter | Geometric Coefficient of Variation 64.653 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-24 | 8.67 Millimoles per Liter | Geometric Coefficient of Variation 18.128 |
| Part A: GSK1292263 800 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-24 | 0.90 Millimoles per Liter | Geometric Coefficient of Variation 141.078 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-24 | 8.95 Millimoles per Liter | Geometric Coefficient of Variation 33.715 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-13 | 1.48 Millimoles per Liter | Geometric Coefficient of Variation 97.908 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | iAUC 0-24 | 0.53 Millimoles per Liter | Geometric Coefficient of Variation 188.368 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the AUC 0-13, AUC 0-24, Incremental AUC (iAUC) 0-13 and iAUC 0-24 of Glucose | AUC 0-13 | 9.23 Millimoles per Liter | Geometric Coefficient of Variation 39.431 |
95% CI: [-1.8, 2.33]
95% CI: [-1.53, 2.76]
95% CI: [-1.64, 2.54]
95% CI: [-1.39, 2.33]
95% CI: [-2.53, 1.95]
95% CI: [-2.35, 2.3]
95% CI: [-2.48, 2.15]
95% CI: [-1.88, 2.21]
95% CI: [-1.58, 0.87]
95% CI: [-1.41, 1.13]
95% CI: [-1.36, 1.18]
95% CI: [-1.33, 0.91]
95% CI: [-1.68, 0.68]
95% CI: [-1.24, 1.21]
95% CI: [-1.44, 0.95]
95% CI: [-1.72, 0.4]
Primary
Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin
Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Up to Day 1 (24 hours)
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, AUC 0-2 | 1207.17 Pico moles per Liter | Geometric Coefficient of Variation 27.472 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, AUC 0-2 | 3.60 Pico moles per Liter | Geometric Coefficient of Variation 41.288 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, AUC 0-2 | 4.45 Pico moles per Liter | Geometric Coefficient of Variation 32.218 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, iAUC 0-2 | 2.65 Pico moles per Liter | Geometric Coefficient of Variation 49.892 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, AUC 0-2 | 16.76 Pico moles per Liter | Geometric Coefficient of Variation 23.007 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, AUC 0-2 | 29.73 Pico moles per Liter | Geometric Coefficient of Variation 34.698 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, iAUC 0-3 | 146.03 Pico moles per Liter | Geometric Coefficient of Variation 52.193 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, iAUC 0-2 | 25.30 Pico moles per Liter | Geometric Coefficient of Variation 36.096 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, iAUC 0-2 | 5.89 Pico moles per Liter | Geometric Coefficient of Variation 62.399 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, AUC 0-3 | 204.77 Pico moles per Liter | Geometric Coefficient of Variation 46.353 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, AUC 0-2 | 2.12 Pico moles per Liter | Geometric Coefficient of Variation 0.426 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, iAUC 0-2 | 563.75 Pico moles per Liter | Geometric Coefficient of Variation 46.497 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, iAUC 0-2 | 0.56 Pico moles per Liter | Geometric Coefficient of Variation 448.254 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, iAUC 0-2 | 0.03 Pico moles per Liter | Geometric Coefficient of Variation 331.662 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, iAUC 0-2 | NA Pico moles per Liter | — |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, AUC 0-2 | 2.12 Pico moles per Liter | Geometric Coefficient of Variation 0 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, iAUC 0-2 | 31.50 Pico moles per Liter | Geometric Coefficient of Variation 30.146 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, AUC 0-2 | 4.51 Pico moles per Liter | Geometric Coefficient of Variation 36.731 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, iAUC 0-2 | 676.24 Pico moles per Liter | Geometric Coefficient of Variation 40.442 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, iAUC 0-2 | 1.66 Pico moles per Liter | Geometric Coefficient of Variation 80.669 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, AUC 0-2 | 4.77 Pico moles per Liter | Geometric Coefficient of Variation 40.537 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, AUC 0-2 | 1352.32 Pico moles per Liter | Geometric Coefficient of Variation 28.098 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, AUC 0-2 | 19.30 Pico moles per Liter | Geometric Coefficient of Variation 42.059 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, AUC 0-3 | 230.91 Pico moles per Liter | Geometric Coefficient of Variation 39.743 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, iAUC 0-2 | 0.24 Pico moles per Liter | Geometric Coefficient of Variation -157.518 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, AUC 0-2 | 37.86 Pico moles per Liter | Geometric Coefficient of Variation 26.719 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, iAUC 0-2 | 4.66 Pico moles per Liter | Geometric Coefficient of Variation 95.556 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, iAUC 0-3 | 156.32 Pico moles per Liter | Geometric Coefficient of Variation 41.131 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, iAUC 0-2 | 0.18 Pico moles per Liter | Geometric Coefficient of Variation 158.801 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, AUC 0-2 | 1357.81 Pico moles per Liter | Geometric Coefficient of Variation 20.421 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, iAUC 0-2 | 620.95 Pico moles per Liter | Geometric Coefficient of Variation 41.762 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, AUC 0-2 | 34.82 Pico moles per Liter | Geometric Coefficient of Variation 34.834 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, iAUC 0-2 | 29.27 Pico moles per Liter | Geometric Coefficient of Variation 37.728 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, AUC 0-2 | 2.18 Pico moles per Liter | Geometric Coefficient of Variation 4.606 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, AUC 0-2 | 5.02 Pico moles per Liter | Geometric Coefficient of Variation 27.985 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, iAUC 0-2 | 2.40 Pico moles per Liter | Geometric Coefficient of Variation 51.939 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, AUC 0-2 | 6.08 Pico moles per Liter | Geometric Coefficient of Variation 39.006 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, iAUC 0-2 | 0.62 Pico moles per Liter | Geometric Coefficient of Variation -157.616 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, AUC 0-3 | 235.88 Pico moles per Liter | Geometric Coefficient of Variation 42.743 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, iAUC 0-3 | 161.05 Pico moles per Liter | Geometric Coefficient of Variation 45.743 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, AUC 0-2 | 22.45 Pico moles per Liter | Geometric Coefficient of Variation 39.164 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, iAUC 0-2 | 6.81 Pico moles per Liter | Geometric Coefficient of Variation 74.605 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, iAUC 0-2 | 0.18 Pico moles per Liter | Geometric Coefficient of Variation 331.662 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, AUC 0-2 | 4.49 Pico moles per Liter | Geometric Coefficient of Variation 44.216 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, AUC 0-2 | 2.14 Pico moles per Liter | Geometric Coefficient of Variation 2.54 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, iAUC 0-2 | 0.73 Pico moles per Liter | Geometric Coefficient of Variation -122.368 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, iAUC 0-2 | 33.51 Pico moles per Liter | Geometric Coefficient of Variation 29.808 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, AUC 0-2 | 1387.78 Pico moles per Liter | Geometric Coefficient of Variation 25.473 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, AUC 0-3 | 254.61 Pico moles per Liter | Geometric Coefficient of Variation 50.81 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, AUC 0-2 | 42.25 Pico moles per Liter | Geometric Coefficient of Variation 34.507 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, iAUC 0-3 | 179.93 Pico moles per Liter | Geometric Coefficient of Variation 58.35 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, iAUC 0-2 | 695.31 Pico moles per Liter | Geometric Coefficient of Variation 43.06 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, iAUC 0-2 | 5.59 Pico moles per Liter | Geometric Coefficient of Variation 62.823 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, AUC 0-2 | 5.59 Pico moles per Liter | Geometric Coefficient of Variation 37.459 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, AUC 0-2 | 23.42 Pico moles per Liter | Geometric Coefficient of Variation 25.206 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, iAUC 0-2 | 2.38 Pico moles per Liter | Geometric Coefficient of Variation 49.604 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, AUC 0-2 | 2.97 Pico moles per Liter | Geometric Coefficient of Variation 34.891 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, iAUC 0-2 | 1.25 Pico moles per Liter | Geometric Coefficient of Variation 162.044 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, AUC 0-2 | 3.85 Pico moles per Liter | Geometric Coefficient of Variation 62.26 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, AUC 0-2 | 4.73 Pico moles per Liter | Geometric Coefficient of Variation 22.23 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 total, iAUC 0-2 | 1.26 Pico moles per Liter | Geometric Coefficient of Variation 63.785 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, AUC 0-2 | 1287.66 Pico moles per Liter | Geometric Coefficient of Variation 34.527 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, iAUC 0-3 | 150.33 Pico moles per Liter | Geometric Coefficient of Variation 56.399 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Glucagon, iAUC 0-2 | 0.39 Pico moles per Liter | Geometric Coefficient of Variation -121.494 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, iAUC 0-2 | 21.79 Pico moles per Liter | Geometric Coefficient of Variation 45.161 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | C-peptide, iAUC 0-2 | 692.11 Pico moles per Liter | Geometric Coefficient of Variation 45.456 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GLP-1 active, iAUC 0-2 | 2.47 Pico moles per Liter | Geometric Coefficient of Variation 38.584 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | PYY total, AUC 0-2 | 13.93 Pico moles per Liter | Geometric Coefficient of Variation 35.971 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | Insulin, AUC 0-3 | 213.17 Pico moles per Liter | Geometric Coefficient of Variation 49.48 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-2) and iAUC(0-2)- C-peptide, Total GIP, GLP-1 (Active and Total), Glucagon and Total PYY and AUC 0-3 and iAUC 0-3 of Insulin | GIP total, AUC 0-2 | 26.57 Pico moles per Liter | Geometric Coefficient of Variation 40.429 |
95% CI: [-200.57, 506.49]
95% CI: [-252.69, 480.42]
95% CI: [-250.89, 479.83]
95% CI: [-186.32, 459.6]
95% CI: [-127.31, 454.55]
95% CI: [-243.57, 359.72]
95% CI: [-222.32, 379]
95% CI: [-108.73, 422.82]
95% CI: [-4.79, 17.87]
95% CI: [-7.65, 15.84]
95% CI: [1.33, 24.74]
95% CI: [-13.17, 7.52]
95% CI: [-3.47, 15.93]
95% CI: [-5.46, 14.65]
95% CI: [-0.54, 19.51]
95% CI: [-11.65, 6.08]
95% CI: [-0.38, 0.52]
95% CI: [-0.21, 0.72]
95% CI: [-0.42, 0.51]
95% CI: [2.28, 3.11]
95% CI: [-0.36, 0.5]
95% CI: [-0.2, 0.69]
95% CI: [-0.41, 0.47]
95% CI: [2.25, 3.04]
95% CI: [-1.44, 1.55]
95% CI: [-1.28, 1.82]
95% CI: [-0.65, 2.44]
95% CI: [-2.85, -0.12]
95% CI: [-1.18, 1.34]
95% CI: [-0.97, 1.63]
95% CI: [-1.48, 1.12]
95% CI: [-2.34, -0.04]
95% CI: [-1.51, 3.98]
95% CI: [0.04, 5.71]
95% CI: [-1.21, 4.16]
95% CI: [-2.2, 2.74]
95% CI: [-4.92, 0.56]
95% CI: [-4.74, 0.93]
95% CI: [-3.74, 1.63]
95% CI: [-3.72, 1.22]
95% CI: [-95.82, 122.59]
95% CI: [-103.25, 123.21]
95% CI: [-80.43, 145.28]
95% CI: [-76.77, 122.76]
95% CI: [-86.79, 90.97]
95% CI: [-92.47, 91.84]
95% CI: [-71.8, 111.91]
95% CI: [-57.59, 104.8]
95% CI: [-3.13, 10.14]
95% CI: [0.41, 14.18]
95% CI: [0.15, 13.87]
95% CI: [-8.62, 3.51]
95% CI: [-2.13, 7.17]
95% CI: [0.47, 10.12]
95% CI: [-3.08, 6.53]
95% CI: [-7.75, 0.74]
Primary
Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose
Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Up to Day 1 (24 hours)
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | AUC 0-3 | 12.82 Millimoles per Liter | Geometric Coefficient of Variation 14.08 |
| Part A: Placebo | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | iAUC 0-3 | 5.55 Millimoles per Liter | Geometric Coefficient of Variation 16.251 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | AUC 0-3 | 12.79 Millimoles per Liter | Geometric Coefficient of Variation 18.904 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | iAUC 0-3 | 5.17 Millimoles per Liter | Geometric Coefficient of Variation 19.811 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | AUC 0-3 | 12.12 Millimoles per Liter | Geometric Coefficient of Variation 16.572 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | iAUC 0-3 | 4.78 Millimoles per Liter | Geometric Coefficient of Variation 20.419 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | iAUC 0-3 | 4.25 Millimoles per Liter | Geometric Coefficient of Variation 27.727 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | AUC 0-3 | 11.26 Millimoles per Liter | Geometric Coefficient of Variation 16.651 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | AUC 0-3 | 11.97 Millimoles per Liter | Geometric Coefficient of Variation 25.95 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT AUC (0-3) and iAUC(0-3)-Glucose | iAUC 0-3 | 4.43 Millimoles per Liter | Geometric Coefficient of Variation 28.677 |
95% CI: [-2.69, 1.56]
95% CI: [-3.05, 1.36]
95% CI: [-3.37, 1.02]
95% CI: [-2.56, 1.33]
95% CI: [-1.64, 0.39]
95% CI: [-2.01, 0.09]
95% CI: [-2.15, -0.06]
95% CI: [-1.91, -0.07]
Primary
Part A: Summary of the OGTT Derived Parameters: Disposition Index
Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated by multiplying insulin glucose index with insulin sensitivity index. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Up to Day 1 (24 hours)
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Summary of the OGTT Derived Parameters: Disposition Index | 0.87 [(µIU/mL)/(mg/deciliter [dL])]^2 | Geometric Coefficient of Variation 201.883 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT Derived Parameters: Disposition Index | 0.76 [(µIU/mL)/(mg/deciliter [dL])]^2 | Geometric Coefficient of Variation 65.975 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT Derived Parameters: Disposition Index | 1.07 [(µIU/mL)/(mg/deciliter [dL])]^2 | Geometric Coefficient of Variation 78.991 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT Derived Parameters: Disposition Index | 0.94 [(µIU/mL)/(mg/deciliter [dL])]^2 | Geometric Coefficient of Variation 62.371 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT Derived Parameters: Disposition Index | 0.86 [(µIU/mL)/(mg/deciliter [dL])]^2 | Geometric Coefficient of Variation 95.526 |
95% CI: [-0.84, 1.32]
95% CI: [-0.6, 1.64]
95% CI: [-1.17, 1.06]
95% CI: [-0.81, 1.16]
Primary
Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio
Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as insulin/glucose ratio was calculated as insulin AUC(0-3\]/glucose AUC(0-3) during OGTT, while glucose/insulin ratio was calculated as glucose AUC(0-3)/insulin AUC(0-3) during OGTT. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Up to Day 1 (24 hours)
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | G/I ratio | 0.06 Ratio | Geometric Coefficient of Variation 60.128 |
| Part A: Placebo | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | I/G ratio | 15.98 Ratio | Geometric Coefficient of Variation 47.582 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | G/I ratio | 0.06 Ratio | Geometric Coefficient of Variation 73.172 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | I/G ratio | 18.05 Ratio | Geometric Coefficient of Variation 40.272 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | G/I ratio | 0.05 Ratio | Geometric Coefficient of Variation 61.602 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | I/G ratio | 19.46 Ratio | Geometric Coefficient of Variation 50.494 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | I/G ratio | 22.61 Ratio | Geometric Coefficient of Variation 60.152 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | G/I ratio | 0.04 Ratio | Geometric Coefficient of Variation 56.203 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | G/I ratio | 0.06 Ratio | Geometric Coefficient of Variation 154.204 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT Derived Parameters: Glucose/Insulin and Insulin/Glucose Ratio | I/G ratio | 17.80 Ratio | Geometric Coefficient of Variation 54.449 |
95% CI: [-0.08, 0.06]
95% CI: [-0.07, 0.07]
95% CI: [-0.07, 0.07]
95% CI: [-0.04, 0.08]
95% CI: [-8.31, 12.85]
95% CI: [-8.01, 13.93]
95% CI: [-4.88, 16.99]
95% CI: [-5.65, 13.68]
Primary
Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index
Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as insulin (30 min) - insulin (0 min)/glucose (30 min) - glucose (0 min). It was calculated as insulin (30 min) - insulin (0 min)/glucose (30 min) - glucose (0 min). The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Up to Day 1 (24 hours)
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index | 0.23 µIU/mL/mg/dL | Geometric Coefficient of Variation 144.722 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index | 0.22 µIU/mL/mg/dL | Geometric Coefficient of Variation 54.34 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index | 0.28 µIU/mL/mg/dL | Geometric Coefficient of Variation 67.645 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index | 0.26 µIU/mL/mg/dL | Geometric Coefficient of Variation 64.622 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index | 0.21 µIU/mL/mg/dL | Geometric Coefficient of Variation 75.325 |
95% CI: [-0.28, 0.22]
95% CI: [-0.2, 0.31]
95% CI: [-0.29, 0.23]
95% CI: [-0.27, 0.19]
Primary
Part A: Summary of the OGTT Derived Parameters: Insulin Sensitivity Index
Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. When this results in multiple samples at the same time point, only one sample was collected. It was calculated as 10,000/square root (\[mean plasma insulin × mean plasma glucose during OGTT or meal challenge\] × \[fasting plasma glucose × fasting plasma insulin\]). The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Up to Day 1 (24 hours)
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part A: Summary of the OGTT Derived Parameters: Insulin Sensitivity Index | 3.95 1/(mg/dL)×1/(µIU/mL) | Geometric Coefficient of Variation 44.078 |
| Part A: GSK1292263 25 mg | Part A: Summary of the OGTT Derived Parameters: Insulin Sensitivity Index | 3.47 1/(mg/dL)×1/(µIU/mL) | Geometric Coefficient of Variation 45.993 |
| Part A: GSK1292263 150 mg | Part A: Summary of the OGTT Derived Parameters: Insulin Sensitivity Index | 3.87 1/(mg/dL)×1/(µIU/mL) | Geometric Coefficient of Variation 42.72 |
| Part A: GSK1292263 800 mg | Part A: Summary of the OGTT Derived Parameters: Insulin Sensitivity Index | 3.60 1/(mg/dL)×1/(µIU/mL) | Geometric Coefficient of Variation 37.292 |
| Part A: Sitagliptin 100 mg | Part A: Summary of the OGTT Derived Parameters: Insulin Sensitivity Index | 4.01 1/(mg/dL)×1/(µIU/mL) | Geometric Coefficient of Variation 47.046 |
95% CI: [-2.06, 1.37]
95% CI: [-1.82, 1.73]
95% CI: [-2.16, 1.38]
95% CI: [-1.43, 1.7]
Primary
Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag)
The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. Blood samples for the determination of PK was collected on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours.
Time frame: Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 14 and 24 hours on Day 1 of each treatment period
Population: Pharmacokinetic Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Placebo | Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag) | T-lag | 0.50 Hour |
| Part A: Placebo | Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag) | T-max | 4.99 Hour |
| Part A: GSK1292263 25 mg | Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag) | T-lag | 0.00 Hour |
| Part A: GSK1292263 25 mg | Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag) | T-max | 3.00 Hour |
| Part A: GSK1292263 150 mg | Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag) | T-lag | 0.00 Hour |
| Part A: GSK1292263 150 mg | Part A: Summary of Time to Maximum Concentration (T-max) and Lag Time Before Observation of Drug Concentration in Sampled Matrix (T-lag) | T-max | 3.00 Hour |
Primary
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI
Clinical chemistry parameters included BUN, potassium, AST, total and direct bilirubin, creatinine, chloride, ALT, uric acid, glucose fasting, GGT, albumin, sodium, magnesium, phosphorus inorganic, calcium, total CO2, ALP, triglycerides, total cholesterol, LDL cholesterol, free fatty acid (NEFA), HDL cholesterol and total protein. It was assessed on Screening, Day -2 (can be non-fasting) and prior to breakfast (early in the morning, fasting) on Days 1, 7 and 14, and on Day 15 prior to checkout, (=24 hours post-dose) of each treatment period and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented.
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Calcium, Low | 1 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Sodium, Low | 0 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 5 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | ALT, High | 0 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Albumin, Low | 1 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Potassium, Low | 0 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, High | 1 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Phosphorus inorganic, Low | 0 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Sodium, Low | 1 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | ALT, High | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, High | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 1 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Phosphorus inorganic, Low | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Calcium, Low | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Albumin, Low | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Potassium, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, High | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | ALT, High | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Calcium, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Sodium, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 4 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Albumin, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Potassium, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Phosphorus inorganic, Low | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | ALT, High | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Phosphorus inorganic, Low | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, High | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 4 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Potassium, Low | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Albumin, Low | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Calcium, Low | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Sodium, Low | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Potassium, Low | 1 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 1 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Albumin, Low | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 3 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Sodium, Low | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Calcium, Low | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, High | 1 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Phosphorus inorganic, Low | 1 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | ALT, High | 1 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Phosphorus inorganic, Low | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, Low | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | ALT, High | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Sodium, Low | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Calcium, Low | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Albumin, Low | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Glucose, High | 3 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | Potassium, Low | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | CO2, High | 1 Participants |
Primary
Part C: Number of Participants With Abnormal Hematology Parameters of PCI
Hematology parameters included platelet count, RBC count, MCV, total neutrophils, WBC absolute, MCH, lymphocytes, MCHC, monocytes, hemoglobin, eosinophils, hematocrit, reticulocytes and basophils. It was assessed on Screening, Day -2 (can be non-fasting) and prior to breakfast (early in the morning, fasting) on Days 1, 7 and 14, and on Day 15 prior to checkout, (=24 hours post-dose) of each treatment period and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented.
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hemoglobin, High | 0 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hematocrit, High | 0 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Total neutrophils, Low | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hemoglobin, High | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hematocrit, High | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Total neutrophils, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hemoglobin, High | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hematocrit, High | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Total neutrophils, Low | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hemoglobin, High | 2 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hematocrit, High | 1 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Total neutrophils, Low | 2 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hemoglobin, High | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hematocrit, High | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Total neutrophils, Low | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hematocrit, High | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Total neutrophils, Low | 1 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Hematology Parameters of PCI | Hemoglobin, High | 2 Participants |
Primary
Part C: Number of Participants With Abnormal Vital Signs of PCI
SBP, DBP and pulse rate measurements were recorded at each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes. Participants with abnormal clinically significant vital signs findings is presented. It was assessed on Screening, on Days -1 to 14 in a fasting state early in the morning (prior to morning dosing on days 1-14) and at Follow-up. On Days 1, 7, 13 and 14, it was also taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose each treatment period and Follow-up (7 to 10 days after final discharge).
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, High | 0 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, Low | 0 Participants |
| Part A: Placebo | Part C: Number of Participants With Abnormal Vital Signs of PCI | Pulse rate, High | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, High | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, Low | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | Pulse rate, High | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, High | 1 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, Low | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | Pulse rate, High | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, High | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, Low | 1 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | Pulse rate, High | 1 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, High | 2 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, Low | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | Pulse rate, High | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, Low | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | Pulse rate, High | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Abnormal Vital Signs of PCI | SBP, High | 0 Participants |
Primary
Part C: Number of Participants With AEs and SAEs
An AE was defined as any untoward MO in a participant temporally associated with the use of a MP, whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Part C: Number of Participants With AEs and SAEs | Any AE | 4 Participants |
| Part A: Placebo | Part C: Number of Participants With AEs and SAEs | Any SAE | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With AEs and SAEs | Any AE | 5 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With AEs and SAEs | Any SAE | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With AEs and SAEs | Any AE | 1 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With AEs and SAEs | Any SAE | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With AEs and SAEs | Any AE | 4 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With AEs and SAEs | Any SAE | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With AEs and SAEs | Any AE | 4 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With AEs and SAEs | Any SAE | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With AEs and SAEs | Any AE | 2 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With AEs and SAEs | Any SAE | 0 Participants |
Primary
Part C: Number of Participants With Significant ECG Abnormalities
Twelve-lead ECGs was obtained in a supine position at each time point during the study using an ECG machine that automatically measured PR, QRS, QT and QTc intervals (QTcB and QTcF). Participants with abnormal clinically significant ECG findings is presented. It was assessed on Screening, on Day -1, 1, 7, 13 and 14 pre-breakfast dose (fasting) and at 1, 3, 6, 9, 12 and 24 hours of each treatment period and Follow-up (7 to 10 days after final discharge).
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part C: Number of Participants With Significant ECG Abnormalities | 0 Participants |
| Part A: GSK1292263 25 mg | Part C: Number of Participants With Significant ECG Abnormalities | 0 Participants |
| Part A: GSK1292263 150 mg | Part C: Number of Participants With Significant ECG Abnormalities | 0 Participants |
| Part A: GSK1292263 800 mg | Part C: Number of Participants With Significant ECG Abnormalities | 0 Participants |
| Part A: Sitagliptin 100 mg | Part C: Number of Participants With Significant ECG Abnormalities | 0 Participants |
| Part C: Sitagliptin 100 mg | Part C: Number of Participants With Significant ECG Abnormalities | 0 Participants |
Primary
Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity
Blood samples for the determination of insulin were collected fasting pre-breakfast and then pre-morning dose (PD time 0) on Days -1, 13 and 14, and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (approximately 4 hour post-morning dose) samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected (example: 24 hours post first-dose = pre-dose \[time 0\] for the second dose).
Time frame: Day -1, 13 and 14
Population: PK/PD Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 13 | 5.6 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 64 |
| Part A: Placebo | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day -1 | 6.4 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 149 |
| Part A: Placebo | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 14 | 5.7 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 88 |
| Part A: GSK1292263 25 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 13 | 8.6 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 50 |
| Part A: GSK1292263 25 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day -1 | 9.8 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 100 |
| Part A: GSK1292263 25 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 14 | 9.0 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 52 |
| Part A: GSK1292263 150 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 13 | 8.7 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 99 |
| Part A: GSK1292263 150 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day -1 | 9.2 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 80 |
| Part A: GSK1292263 150 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 14 | 7.3 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 90 |
| Part A: GSK1292263 800 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 13 | 7.2 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 72 |
| Part A: GSK1292263 800 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day -1 | 8.0 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 96 |
| Part A: GSK1292263 800 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 14 | 8.0 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 75 |
| Part A: Sitagliptin 100 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day -1 | 6.6 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 79 |
| Part A: Sitagliptin 100 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 14 | 6.8 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 91 |
| Part A: Sitagliptin 100 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 13 | 6.6 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 59 |
| Part C: Sitagliptin 100 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 14 | 5.7 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 124 |
| Part C: Sitagliptin 100 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day 13 | 7.4 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 122 |
| Part C: Sitagliptin 100 mg | Part C: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity | Day -1 | 7.0 mL/min×1/µIU×10^4 | Geometric Coefficient of Variation 107 |
Primary
Part C: Summary of Accumulation Ratio (Ro)
Ro was derived as follows: Ro = Day 13 (AUC0-24)/Day 1 (AUC0-24) for once daily dosing; Ro = Day 13 AM (AUC0-10)/Day 1 AM (AUC0-10) for BID dosing and Ro = Day 13 (AUC0-24)/Day 1 (AUC0-24) for BID dosing. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. Data presented for Day 13 and Day 14.
Time frame: Days 1, 7, 13 and 14
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Summary of Accumulation Ratio (Ro) | Day 13 | 2.22 Ratio | Geometric Coefficient of Variation 21.131 |
| Part A: Placebo | Part C: Summary of Accumulation Ratio (Ro) | Day 14 | 2.29 Ratio | Geometric Coefficient of Variation 19.681 |
| Part A: GSK1292263 25 mg | Part C: Summary of Accumulation Ratio (Ro) | Day 14 | 2.15 Ratio | Geometric Coefficient of Variation 20.319 |
| Part A: GSK1292263 25 mg | Part C: Summary of Accumulation Ratio (Ro) | Day 13 | 2.17 Ratio | Geometric Coefficient of Variation 19.972 |
| Part A: GSK1292263 150 mg | Part C: Summary of Accumulation Ratio (Ro) | Day 13 | 1.72 Ratio | Geometric Coefficient of Variation 31.647 |
| Part A: GSK1292263 150 mg | Part C: Summary of Accumulation Ratio (Ro) | Day 14 | 1.77 Ratio | Geometric Coefficient of Variation 31.51 |
| Part A: GSK1292263 800 mg | Part C: Summary of Accumulation Ratio (Ro) | Day 13 | 1.29 Ratio | Geometric Coefficient of Variation 40.69 |
| Part A: GSK1292263 800 mg | Part C: Summary of Accumulation Ratio (Ro) | Day 14 | 1.39 Ratio | Geometric Coefficient of Variation 39.448 |
Primary
Part C: Summary of AUC0-10, AUC0-12 and AUC0-24
The AUC0-10, AUC0-12 and AUC0-24 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For QD and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post- breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.
Time frame: Days 1, 7, 13 and 14
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 1 | 1127.45 Ratio | Geometric Coefficient of Variation 10.341 |
| Part A: Placebo | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 13 | 7776.26 Ratio | Geometric Coefficient of Variation 23.727 |
| Part A: Placebo | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 1 | 3552.46 Ratio | Geometric Coefficient of Variation 15.595 |
| Part A: Placebo | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 13 | 3167.19 Ratio | Geometric Coefficient of Variation 21.745 |
| Part A: Placebo | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 14 | 8026.26 Ratio | Geometric Coefficient of Variation 22.275 |
| Part A: Placebo | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 14 | 3179.51 Ratio | Geometric Coefficient of Variation 22.197 |
| Part A: Placebo | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-12, Day 7 | 3559.59 Ratio | Geometric Coefficient of Variation 27.687 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 13 | 14463.50 Ratio | Geometric Coefficient of Variation 29.668 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-12, Day 7 | 6413.05 Ratio | Geometric Coefficient of Variation 31.719 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 14 | 5723.55 Ratio | Geometric Coefficient of Variation 32.728 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 1 | 6439.56 Ratio | Geometric Coefficient of Variation 26.152 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 14 | 14356.75 Ratio | Geometric Coefficient of Variation 29.796 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 13 | 5869.82 Ratio | Geometric Coefficient of Variation 32.289 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 1 | 1868.87 Ratio | Geometric Coefficient of Variation 24.974 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-12, Day 7 | 9965.14 Ratio | Geometric Coefficient of Variation 27.26 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 1 | 3076.52 Ratio | Geometric Coefficient of Variation 23.023 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 13 | 7332.26 Ratio | Geometric Coefficient of Variation 32.746 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 14 | 7451.13 Ratio | Geometric Coefficient of Variation 37.067 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 1 | 11078.97 Ratio | Geometric Coefficient of Variation 24.411 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 13 | 18682.34 Ratio | Geometric Coefficient of Variation 32.153 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 14 | 19134.61 Ratio | Geometric Coefficient of Variation 34.542 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 14 | 5470.57 Ratio | Geometric Coefficient of Variation 23.708 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 14 | 10166.83 Ratio | Geometric Coefficient of Variation 26.747 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 13 | 9388.93 Ratio | Geometric Coefficient of Variation 26.616 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 13 | 5348.21 Ratio | Geometric Coefficient of Variation 22.627 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-10, Day 1 | 4003.80 Ratio | Geometric Coefficient of Variation 27.722 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-24, Day 1 | 7153.16 Ratio | Geometric Coefficient of Variation 34.663 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-10, AUC0-12 and AUC0-24 | AUC 0-12, Day 7 | 6268.95 Ratio | Geometric Coefficient of Variation 27.159 |
Primary
Part C: Summary of Change From Baseline in Fasted Glucose
Blood samples were collected fasting pre-breakfast and pre-morning dose (PD time 0) on Days -1, 13 and 14 and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (4 hour post-morning dose) samples were collected just before the meal and after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value minus post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Baseline (Day 1 pre-dose) and Day -1, 13 and 14.
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 1 Hour | 4.60 Millimoles per Liter | Geometric Coefficient of Variation 73.478 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 10 Hours | 2.07 Millimoles per Liter | Geometric Coefficient of Variation 271.597 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 2 Hours | 4.71 Millimoles per Liter | Geometric Coefficient of Variation 150.72 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Glucose | Day 14, 24 Hours | 1.26 Millimoles per Liter | Geometric Coefficient of Variation -1044.892 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 4 Hours | 1.85 Millimoles per Liter | Geometric Coefficient of Variation -482.69 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 12 Hours | 3.66 Millimoles per Liter | Geometric Coefficient of Variation 105.362 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 6 Hours | 4.98 Millimoles per Liter | Geometric Coefficient of Variation 75.579 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 2 Hours | 3.65 Millimoles per Liter | Geometric Coefficient of Variation 82.667 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 6 Hours | 3.72 Millimoles per Liter | Geometric Coefficient of Variation 67.064 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 4 Hours | 1.11 Millimoles per Liter | Geometric Coefficient of Variation -606.064 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 10 Hours | 1.91 Millimoles per Liter | Geometric Coefficient of Variation 166.934 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 1 Hour | 4.93 Millimoles per Liter | Geometric Coefficient of Variation 41.905 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 14, 24 Hours | 1.09 Millimoles per Liter | Geometric Coefficient of Variation 3884.234 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 12 Hours | 2.42 Millimoles per Liter | Geometric Coefficient of Variation 71.838 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 4 Hours | 1.13 Millimoles per Liter | Geometric Coefficient of Variation 270.863 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 2 Hours | 5.00 Millimoles per Liter | Geometric Coefficient of Variation 45.953 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 1 Hour | 7.39 Millimoles per Liter | Geometric Coefficient of Variation 36.73 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 10 Hours | 3.18 Millimoles per Liter | Geometric Coefficient of Variation 83.271 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 12 Hours | 4.41 Millimoles per Liter | Geometric Coefficient of Variation 49.106 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 6 Hours | 6.16 Millimoles per Liter | Geometric Coefficient of Variation 51.414 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 14, 24 Hours | 1.34 Millimoles per Liter | Geometric Coefficient of Variation 179.562 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 6 Hours | 4.15 Millimoles per Liter | Geometric Coefficient of Variation 74.614 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 1 Hour | 5.17 Millimoles per Liter | Geometric Coefficient of Variation 57.754 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 2 Hours | 3.61 Millimoles per Liter | Geometric Coefficient of Variation 75.258 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 4 Hours | 2.05 Millimoles per Liter | Geometric Coefficient of Variation 685.731 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 10 Hours | 3.13 Millimoles per Liter | Geometric Coefficient of Variation 133.236 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 12 Hours | 3.53 Millimoles per Liter | Geometric Coefficient of Variation 82.377 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 14, 24 Hours | 1.21 Millimoles per Liter | Geometric Coefficient of Variation 2819.22 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 4 Hours | 0.95 Millimoles per Liter | Geometric Coefficient of Variation -223.367 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 2 Hours | 2.59 Millimoles per Liter | Geometric Coefficient of Variation 60.658 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 14, 24 Hours | 1.52 Millimoles per Liter | Geometric Coefficient of Variation 565.287 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 1 Hour | 5.51 Millimoles per Liter | Geometric Coefficient of Variation 38.497 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 12 Hours | 3.77 Millimoles per Liter | Geometric Coefficient of Variation 60.67 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 6 Hours | 3.93 Millimoles per Liter | Geometric Coefficient of Variation 62.647 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 10 Hours | 2.06 Millimoles per Liter | Geometric Coefficient of Variation 228.901 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 14, 24 Hours | 2.08 Millimoles per Liter | Geometric Coefficient of Variation -323.555 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 10 Hours | 5.17 Millimoles per Liter | Geometric Coefficient of Variation -1115.737 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 4 Hours | 2.13 Millimoles per Liter | Geometric Coefficient of Variation -188.101 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 2 Hours | 3.17 Millimoles per Liter | Geometric Coefficient of Variation 152.623 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 12 Hours | 3.33 Millimoles per Liter | Geometric Coefficient of Variation 119.827 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 1 Hour | 4.09 Millimoles per Liter | Geometric Coefficient of Variation 70.342 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Glucose | Day 7, 6 Hours | 3.70 Millimoles per Liter | Geometric Coefficient of Variation 270.326 |
95% CI: [-3.04, 2]
95% CI: [-3.07, 1.94]
95% CI: [-0.45, 4.57]
95% CI: [-2.19, 2.82]
95% CI: [-3.99, 1.02]
95% CI: [-3.27, 1.68]
95% CI: [-2.78, 2.15]
95% CI: [-0.03, 4.91]
95% CI: [-1.58, 3.34]
95% CI: [-3.69, 1.24]
95% CI: [-2.06, 2.03]
95% CI: [-1.56, 2.51]
95% CI: [-0.53, 3.55]
95% CI: [-0.8, 3.26]
95% CI: [-3.05, 1.02]
95% CI: [-3.05, 2.67]
95% CI: [-2.39, 3.3]
95% CI: [-0.14, 5.56]
95% CI: [-1.78, 3.91]
95% CI: [-5.55, 0.14]
95% CI: [-2.41, 2.7]
95% CI: [-2.09, 2.99]
95% CI: [-0.13, 4.96]
95% CI: [-1.47, 3.6]
95% CI: [-4.05, 1.03]
95% CI: [-4.2, 1.6]
95% CI: [-4.21, 1.56]
95% CI: [-1.89, 3.89]
95% CI: [-3.14, 2.62]
95% CI: [-3.4, 2.37]
95% CI: [-2.29, 1.26]
95% CI: [-1.99, 1.55]
95% CI: [-1.28, 2.28]
95% CI: [-1.98, 1.65]
95% CI: [-2.81, 0.73]
Primary
Part C: Summary of Change From Baseline in Fasted Insulin
Blood samples were collected fasting pre-breakfast and pre-morning dose (PD time 0) on Days -1, 13 and 14 and then at 10, 20, 30, 60, 90, 120, 180 min after eating the standardized breakfast meal tolerance test. For lunch (4 hour post-morning dose) samples were collected just before the meal and after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (10 hour post-morning dose), BID dosing groups followed the sequence of sampling, food and dosing as for breakfast (PD sample immediately before meal, eat and then dose), then 0.5, 1, 1.5, 2 and 3 hours post-dinner. A sample was also collected 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value minus post-Baseline value. The point estimates and corresponding 95% CI for treatment ratios were calculated for treatment comparisons versus placebo.
Time frame: Baseline (Day 1 pre-dose) and Day -1, 13 and 14
Population: The PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 1 Hour | 158.91 Millimoles per Liter | Geometric Coefficient of Variation 115.808 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 10 Hours | 68.08 Millimoles per Liter | Geometric Coefficient of Variation 129.341 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 2 Hours | 92.17 Millimoles per Liter | Geometric Coefficient of Variation 99.479 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Insulin | Day 14, 24 Hours | 12.45 Millimoles per Liter | Geometric Coefficient of Variation -180.869 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 4 Hours | 35.05 Millimoles per Liter | Geometric Coefficient of Variation 650.532 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 12 Hours | 107.52 Millimoles per Liter | Geometric Coefficient of Variation 77.742 |
| Part A: Placebo | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 6 Hours | 103.52 Millimoles per Liter | Geometric Coefficient of Variation 76.383 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 2 Hours | 94.18 Millimoles per Liter | Geometric Coefficient of Variation 55.907 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 6 Hours | 88.70 Millimoles per Liter | Geometric Coefficient of Variation 70.484 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 4 Hours | 20.10 Millimoles per Liter | Geometric Coefficient of Variation 354.147 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 10 Hours | 55.28 Millimoles per Liter | Geometric Coefficient of Variation 131.603 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 1 Hour | 117.15 Millimoles per Liter | Geometric Coefficient of Variation 53.056 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 14, 24 Hours | 1.51 Millimoles per Liter | Geometric Coefficient of Variation -256.494 |
| Part A: GSK1292263 25 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 12 Hours | 95.16 Millimoles per Liter | Geometric Coefficient of Variation 69.323 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 4 Hours | 27.32 Millimoles per Liter | Geometric Coefficient of Variation 97.622 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 2 Hours | 143.75 Millimoles per Liter | Geometric Coefficient of Variation 108.953 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 1 Hour | 151.56 Millimoles per Liter | Geometric Coefficient of Variation 88.163 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 10 Hours | 55.40 Millimoles per Liter | Geometric Coefficient of Variation 86.768 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 12 Hours | 98.26 Millimoles per Liter | Geometric Coefficient of Variation 140.843 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 6 Hours | 136.15 Millimoles per Liter | Geometric Coefficient of Variation 92.906 |
| Part A: GSK1292263 150 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 14, 24 Hours | 3.54 Millimoles per Liter | Geometric Coefficient of Variation -116.769 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 6 Hours | 131.08 Millimoles per Liter | Geometric Coefficient of Variation 84.834 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 1 Hour | 129.44 Millimoles per Liter | Geometric Coefficient of Variation 101.186 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 2 Hours | 87.30 Millimoles per Liter | Geometric Coefficient of Variation 145.016 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 4 Hours | 21.93 Millimoles per Liter | Geometric Coefficient of Variation 337.965 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 10 Hours | 66.90 Millimoles per Liter | Geometric Coefficient of Variation 162.22 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 12 Hours | 114.93 Millimoles per Liter | Geometric Coefficient of Variation 81.742 |
| Part A: GSK1292263 800 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 14, 24 Hours | 11.03 Millimoles per Liter | Geometric Coefficient of Variation -226.913 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 4 Hours | 19.41 Millimoles per Liter | Geometric Coefficient of Variation 150.506 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 2 Hours | 160.57 Millimoles per Liter | Geometric Coefficient of Variation 123.482 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 14, 24 Hours | 7.87 Millimoles per Liter | Geometric Coefficient of Variation -322.274 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 1 Hour | 216.95 Millimoles per Liter | Geometric Coefficient of Variation 91.593 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 12 Hours | 138.42 Millimoles per Liter | Geometric Coefficient of Variation 54.45 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 6 Hours | 142.10 Millimoles per Liter | Geometric Coefficient of Variation 74.418 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 10 Hours | 64.04 Millimoles per Liter | Geometric Coefficient of Variation 72.943 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 14, 24 Hours | 3.26 Millimoles per Liter | Geometric Coefficient of Variation -191.1 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 10 Hours | 39.35 Millimoles per Liter | Geometric Coefficient of Variation 76.204 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 4 Hours | 30.25 Millimoles per Liter | Geometric Coefficient of Variation 169.388 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 2 Hours | 163.46 Millimoles per Liter | Geometric Coefficient of Variation 80.53 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 12 Hours | 123.65 Millimoles per Liter | Geometric Coefficient of Variation 74.446 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 1 Hour | 162.83 Millimoles per Liter | Geometric Coefficient of Variation 62.028 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Change From Baseline in Fasted Insulin | Day 7, 6 Hours | 130.88 Millimoles per Liter | Geometric Coefficient of Variation 48.541 |
95% CI: [-214.72, 73.8]
95% CI: [-295.98, -7.46]
95% CI: [-213.48, 75.25]
95% CI: [-248.72, 39.78]
95% CI: [-263.93, 27.01]
95% CI: [-264.78, 36.1]
95% CI: [-266.9, 33.98]
95% CI: [-154.75, 146.35]
95% CI: [-198.7, 102.16]
95% CI: [-202.31, 101.1]
95% CI: [-40.84, 26.38]
95% CI: [-38.63, 28.58]
95% CI: [-24.11, 43.16]
95% CI: [-36.22, 30.99]
95% CI: [-13.09, 54.69]
95% CI: [-156.11, 38.38]
95% CI: [-175.15, 19.35]
95% CI: [-69, 125.65]
95% CI: [-121.74, 72.74]
95% CI: [-157.82, 38.31]
95% CI: [-69.85, 69.4]
95% CI: [-77.28, 61.98]
95% CI: [-62.55, 76.85]
95% CI: [-36.89, 102.36]
95% CI: [-81.01, 61.49]
95% CI: [-123.36, 84.18]
95% CI: [-150.69, 56.85]
95% CI: [-79.16, 128.59]
95% CI: [-111.73, 95.8]
95% CI: [-103.08, 109.29]
95% CI: [-25.12, 4.89]
95% CI: [-23.71, 6.28]
95% CI: [-15.63, 14.38]
95% CI: [-27.78, 2.88]
95% CI: [-24.02, 6.66]
Primary
Part C: Summary of Plasma Cmax
The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.
Time frame: Days 1, 7, 13 and 14
Population: Pharmacokinetic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Summary of Plasma Cmax | Day 1 | 219.36 Nanograms per millimeter | Geometric Coefficient of Variation 14.14 |
| Part A: Placebo | Part C: Summary of Plasma Cmax | Day 7 | 410.98 Nanograms per millimeter | Geometric Coefficient of Variation 25.083 |
| Part A: Placebo | Part C: Summary of Plasma Cmax | Day 13 | 433.12 Nanograms per millimeter | Geometric Coefficient of Variation 20.372 |
| Part A: Placebo | Part C: Summary of Plasma Cmax | Day 14 | 438.36 Nanograms per millimeter | Geometric Coefficient of Variation 19.487 |
| Part A: GSK1292263 25 mg | Part C: Summary of Plasma Cmax | Day 7 | 715.01 Nanograms per millimeter | Geometric Coefficient of Variation 26.989 |
| Part A: GSK1292263 25 mg | Part C: Summary of Plasma Cmax | Day 13 | 732.05 Nanograms per millimeter | Geometric Coefficient of Variation 29.116 |
| Part A: GSK1292263 25 mg | Part C: Summary of Plasma Cmax | Day 14 | 715.71 Nanograms per millimeter | Geometric Coefficient of Variation 30.769 |
| Part A: GSK1292263 25 mg | Part C: Summary of Plasma Cmax | Day 1 | 364.73 Nanograms per millimeter | Geometric Coefficient of Variation 29.202 |
| Part A: GSK1292263 150 mg | Part C: Summary of Plasma Cmax | Day 13 | 969.19 Nanograms per millimeter | Geometric Coefficient of Variation 31.059 |
| Part A: GSK1292263 150 mg | Part C: Summary of Plasma Cmax | Day 7 | 1149.32 Nanograms per millimeter | Geometric Coefficient of Variation 25.481 |
| Part A: GSK1292263 150 mg | Part C: Summary of Plasma Cmax | Day 14 | 950.52 Nanograms per millimeter | Geometric Coefficient of Variation 35.046 |
| Part A: GSK1292263 150 mg | Part C: Summary of Plasma Cmax | Day 1 | 584.32 Nanograms per millimeter | Geometric Coefficient of Variation 30.096 |
| Part A: GSK1292263 800 mg | Part C: Summary of Plasma Cmax | Day 14 | 772.89 Nanograms per millimeter | Geometric Coefficient of Variation 23.019 |
| Part A: GSK1292263 800 mg | Part C: Summary of Plasma Cmax | Day 7 | 813.03 Nanograms per millimeter | Geometric Coefficient of Variation 24.578 |
| Part A: GSK1292263 800 mg | Part C: Summary of Plasma Cmax | Day 1 | 721.18 Nanograms per millimeter | Geometric Coefficient of Variation 23.346 |
| Part A: GSK1292263 800 mg | Part C: Summary of Plasma Cmax | Day 13 | 831.23 Nanograms per millimeter | Geometric Coefficient of Variation 18.373 |
Primary
Part C: Summary of Time Invariance Ratio (Rs) of AUC0-10 for BID Dose of GSK1292263
The AUC0-10 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.
Time frame: Days 1, 7, 13 and 14
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Placebo | Part C: Summary of Time Invariance Ratio (Rs) of AUC0-10 for BID Dose of GSK1292263 | 2.8174 Ratio |
| Part A: GSK1292263 25 mg | Part C: Summary of Time Invariance Ratio (Rs) of AUC0-10 for BID Dose of GSK1292263 | 3.0033 Ratio |
| Part A: GSK1292263 150 mg | Part C: Summary of Time Invariance Ratio (Rs) of AUC0-10 for BID Dose of GSK1292263 | 2.4218 Ratio |
Primary
Part C: Summary of Time Invariance Ratio (Rs) of AUC0-24 for Once Daily Dose of GSK1292263
The AUC0-24 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.
Time frame: Days 1, 7, 13 and 14
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Part A: Placebo | Part C: Summary of Time Invariance Ratio (Rs) of AUC0-24 for Once Daily Dose of GSK1292263 | 1.2871 Ratio |
Primary
Part C: Summary of Time Invariance Ratio (Rs) of Cmax
The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (=post-breakfast), 1, 2, 4 (=pre lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected. Cmax for one participant from 50 BID x 14 day was not analyzed due to positive definite G Matrix.
Time frame: Days 1, 7, 13 and 14
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part A: Placebo | Part C: Summary of Time Invariance Ratio (Rs) of Cmax | 1.9186 Ratio |
| Part A: GSK1292263 25 mg | Part C: Summary of Time Invariance Ratio (Rs) of Cmax | 1.6755 Ratio |
| Part A: GSK1292263 150 mg | Part C: Summary of Time Invariance Ratio (Rs) of Cmax | 1.1703 Ratio |
Primary
Part C: Summary of T-max and T-lag
The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (=immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.
Time frame: Days 1, 7, 13 and 14
Population: Pharmacokinetic Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Placebo | Part C: Summary of T-max and T-lag | T-max, Day 7 | 3.97 Hour |
| Part A: Placebo | Part C: Summary of T-max and T-lag | T-lag, Day 1 | 0.00 Hour |
| Part A: Placebo | Part C: Summary of T-max and T-lag | T-max, Day 13 | 3.97 Hour |
| Part A: Placebo | Part C: Summary of T-max and T-lag | T-max, Day 1 | 4.00 Hour |
| Part A: Placebo | Part C: Summary of T-max and T-lag | T-max, Day 14 | 4.01 Hour |
| Part A: GSK1292263 25 mg | Part C: Summary of T-max and T-lag | T-max, Day 7 | 3.97 Hour |
| Part A: GSK1292263 25 mg | Part C: Summary of T-max and T-lag | T-max, Day 1 | 12.00 Hour |
| Part A: GSK1292263 25 mg | Part C: Summary of T-max and T-lag | T-max, Day 13 | 3.98 Hour |
| Part A: GSK1292263 25 mg | Part C: Summary of T-max and T-lag | T-lag, Day 1 | 0.00 Hour |
| Part A: GSK1292263 25 mg | Part C: Summary of T-max and T-lag | T-max, Day 14 | 3.98 Hour |
| Part A: GSK1292263 150 mg | Part C: Summary of T-max and T-lag | T-lag, Day 1 | 0.00 Hour |
| Part A: GSK1292263 150 mg | Part C: Summary of T-max and T-lag | T-max, Day 1 | 12.00 Hour |
| Part A: GSK1292263 150 mg | Part C: Summary of T-max and T-lag | T-max, Day 7 | 3.97 Hour |
| Part A: GSK1292263 150 mg | Part C: Summary of T-max and T-lag | T-max, Day 13 | 3.97 Hour |
| Part A: GSK1292263 150 mg | Part C: Summary of T-max and T-lag | T-max, Day 14 | 3.98 Hour |
| Part A: GSK1292263 800 mg | Part C: Summary of T-max and T-lag | T-max, Day 13 | 3.97 Hour |
| Part A: GSK1292263 800 mg | Part C: Summary of T-max and T-lag | T-max, Day 1 | 3.97 Hour |
| Part A: GSK1292263 800 mg | Part C: Summary of T-max and T-lag | T-lag, Day 1 | 0.50 Hour |
| Part A: GSK1292263 800 mg | Part C: Summary of T-max and T-lag | T-max, Day 7 | 4.0 Hour |
| Part A: GSK1292263 800 mg | Part C: Summary of T-max and T-lag | T-max, Day 14 | 3.98 Hour |
Secondary
Part B: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI
Clinical chemistry parameters included BUN, potassium, AST, total and direct bilirubin, creatinine, chloride, ALT, uric acid, glucose fasting, GGT, albumin, sodium, magnesium, phosphorus inorganic, calcium, total CO2, ALP, triglycerides, total cholesterol, LDL cholesterol, free fatty acid (NEFA), HDL cholesterol and total protein. It was assessed on Screening, Day -1, 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters (Glucose, High) for which at least one value of PCI was reported are summarized. Null data is not presented.
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part B: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | 1 Participants |
| Part A: GSK1292263 25 mg | Part B: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI | 1 Participants |
Secondary
Part B: Number of Participants With Abnormal Hematology Parameters of PCI
Hematology parameters included platelet count, RBC count, MCV, total neutrophils, WBC absolute, MCH, lymphocytes, MCHC, monocytes, hemoglobin, eosinophils, hematocrit, reticulocytes and basophils. It was assessed on Screening, Day -1, 2 (of each treatment period) and Follow-up (7 to 10 days after final discharge). Only those parameters for which at least one value of PCI was reported are summarized. Null data is not presented.
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part B: Number of Participants With Abnormal Hematology Parameters of PCI | 0 Participants |
| Part A: GSK1292263 25 mg | Part B: Number of Participants With Abnormal Hematology Parameters of PCI | 0 Participants |
Secondary
Part B: Number of Participants With Abnormal Vital Signs of PCI
SBP, DBP and pulse rate measurements were recorded at each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 min. Participants with abnormal clinically significant vital signs findings is presented. It was assessed on Screening, Day -1, 1, 2 (pre-dose, 1, 3, 4, 6, 10, 16 and 24 hours of each treatment period) and Follow-up (7 -10 days after final discharge).
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part B: Number of Participants With Abnormal Vital Signs of PCI | 0 Participants |
| Part A: GSK1292263 25 mg | Part B: Number of Participants With Abnormal Vital Signs of PCI | 0 Participants |
Secondary
Part B: Number of Participants With AEs and SAEs
An AE was defined as any untoward MO in a participant temporally associated with the use of a MP, whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition.
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Placebo | Part B: Number of Participants With AEs and SAEs | Any AE | 0 Participants |
| Part A: Placebo | Part B: Number of Participants With AEs and SAEs | Any SAE | 0 Participants |
| Part A: GSK1292263 25 mg | Part B: Number of Participants With AEs and SAEs | Any AE | 1 Participants |
| Part A: GSK1292263 25 mg | Part B: Number of Participants With AEs and SAEs | Any SAE | 0 Participants |
Secondary
Part B: Number of Participants With Significant ECG Abnormalities
Twelve-lead ECGs was obtained in a supine position at each time point during the study using an ECG machine that automatically measured PR, QRS, QT and QTc intervals (QTcB and QTcF). Participants with abnormal clinically significant ECG findings is presented. It was assessed on Screening, Day 1 at pre-dose, 1, 2, 3, 4, 6, 10, 16, 24 hours and Follow-up (7 -10 days after final discharge).
Time frame: Up to Week 7
Population: Safety Population.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Placebo | Part B: Number of Participants With Significant ECG Abnormalities | 0 Participants |
| Part A: GSK1292263 25 mg | Part B: Number of Participants With Significant ECG Abnormalities | 0 Participants |
Secondary
Part B: Summary of AUC0-t and AUC0-24
The AUC 0-24 and AUC 0-t determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours.
Time frame: Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours on Day 1 of each treatment period
Population: PK Population.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Summary of AUC0-t and AUC0-24 | AUC 0-24 | 3370.43 Nanograms×hour per mL | Geometric Coefficient of Variation 21.507 |
| Part A: Placebo | Part B: Summary of AUC0-t and AUC0-24 | AUC 0-t | 3370.43 Nanograms×hour per mL | Geometric Coefficient of Variation 21.507 |
| Part A: GSK1292263 25 mg | Part B: Summary of AUC0-t and AUC0-24 | AUC 0-24 | 12639.84 Nanograms×hour per mL | Geometric Coefficient of Variation 27.622 |
| Part A: GSK1292263 25 mg | Part B: Summary of AUC0-t and AUC0-24 | AUC 0-t | 12659.88 Nanograms×hour per mL | Geometric Coefficient of Variation 27.391 |
Secondary
Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin
Blood samples for the determination of glucose and other PD markers were collected at pre-dose on Day 1 of each dosing period. For breakfast, lunch and evening meal in Part B, samples were collected just after the meal and at the following times after starting each meal: 0.5, 1 and 2 hours. Samples were also collected in Part B at 24 hours post-dose. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value from post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 1 (24 hours)
Population: PD Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | GLP-1 ACTIVE | 0.00 Pico moles per Liter | — |
| Part A: Placebo | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | GLUCAGON | 0.94 Pico moles per Liter | — |
| Part A: Placebo | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | GIP TOTAL | 2.23 Pico moles per Liter | Geometric Coefficient of Variation 38.211 |
| Part A: Placebo | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | INSULIN | 31.18 Pico moles per Liter | Geometric Coefficient of Variation 223.783 |
| Part A: Placebo | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | GLP-1 TOTAL | 0.56 Pico moles per Liter | Geometric Coefficient of Variation 384.9 |
| Part A: Placebo | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | PYY TOTAL | 3.05 Pico moles per Liter | Geometric Coefficient of Variation 99.436 |
| Part A: Placebo | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | C-PEPTIDE | 13.44 Pico moles per Liter | Geometric Coefficient of Variation 226.572 |
| Part A: GSK1292263 25 mg | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | PYY TOTAL | 4.55 Pico moles per Liter | Geometric Coefficient of Variation 181.246 |
| Part A: GSK1292263 25 mg | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | C-PEPTIDE | 55.83 Pico moles per Liter | Geometric Coefficient of Variation -507.439 |
| Part A: GSK1292263 25 mg | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | GIP TOTAL | 5.40 Pico moles per Liter | Geometric Coefficient of Variation -165.542 |
| Part A: GSK1292263 25 mg | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | GLP-1 ACTIVE | 0.00 Pico moles per Liter | — |
| Part A: GSK1292263 25 mg | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | GLP-1 TOTAL | 0.48 Pico moles per Liter | Geometric Coefficient of Variation 66.682 |
| Part A: GSK1292263 25 mg | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | GLUCAGON | 2.02 Pico moles per Liter | Geometric Coefficient of Variation 72.451 |
| Part A: GSK1292263 25 mg | Part B: Summary of Change From Baseline in Fasted Glucagon, GLP-1, C-peptide, Total GIP, Total PYY and Insulin | INSULIN | 7.19 Pico moles per Liter | Geometric Coefficient of Variation 7682.607 |
Secondary
Part B: Summary of Change From Baseline in Fasted Glucose
Blood samples for the determination of glucose were collected at pre-dose on Day 1 of each dosing period and immediately prior to and at 10, 20, 30, 60, 90, 120, 180 min after administration of the 75 grams glucose drink. For lunch and evening meal in Part A, samples were collected just before the meal and at the following times after starting each meal: 0.5, 1, 1.5 (except breakfast in Part B), 2 and 3 hours. When this results in multiple samples at the same time point, only one sample was collected. Change from Baseline was calculated by subtracting Baseline value from post-Baseline value.
Time frame: Baseline (Day 1 pre-dose) and Day 1 (24 hours)
Population: The PD Population included participants from the Safety Population who had any PD parameter estimates from any portion of the study.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Summary of Change From Baseline in Fasted Glucose | 0.40 Millimoles per Liter | Geometric Coefficient of Variation 62.025 |
| Part A: GSK1292263 25 mg | Part B: Summary of Change From Baseline in Fasted Glucose | 1.95 Millimoles per Liter | Geometric Coefficient of Variation -10966.01 |
Secondary
Part B: Summary of Plasma Cmax
The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours.
Time frame: Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours on Day 1 of each treatment period.
Population: PK Population.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part B: Summary of Plasma Cmax | 339.52 Nanograms per mL | Geometric Coefficient of Variation 32.581 |
| Part A: GSK1292263 25 mg | Part B: Summary of Plasma Cmax | 944.21 Nanograms per mL | Geometric Coefficient of Variation 47.33 |
Secondary
Part B: Summary of T-max and T-lag
The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. Blood samples for the determination of PK was collected at on Day 1 of each period: immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours.
Time frame: Pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13 and 24 hours on Day 1 of each treatment period
Population: PK Population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Placebo | Part B: Summary of T-max and T-lag | T-max | 2.00 Hour |
| Part A: Placebo | Part B: Summary of T-max and T-lag | T-lag | 0.00 Hour |
| Part A: GSK1292263 25 mg | Part B: Summary of T-max and T-lag | T-max | 4.98 Hour |
| Part A: GSK1292263 25 mg | Part B: Summary of T-max and T-lag | T-lag | 0.00 Hour |
Secondary
Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered
The AUC0-10, AUC0-12 and AUC0-24 determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post- breakfast), 1, 2, 4 (= pre lunch), 6, 10 (= immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.
Time frame: Days 1, 7, 13 and 14
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Placebo | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-24, Day 14 | 2701.81 Nanograms×hour per mL | Geometric Coefficient of Variation 16.951 |
| Part A: Placebo | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-t, Day 14 | 2701.79 Nanograms×hour per mL | Geometric Coefficient of Variation 16.955 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-24, Day 14 | 2585.15 Nanograms×hour per mL | Geometric Coefficient of Variation 18.942 |
| Part A: GSK1292263 25 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-t, Day 14 | 2585.10 Nanograms×hour per mL | Geometric Coefficient of Variation 18.944 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-24, Day 14 | 3338.49 Nanograms×hour per mL | Geometric Coefficient of Variation 25.396 |
| Part A: GSK1292263 150 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-t, Day 14 | 3338.27 Nanograms×hour per mL | Geometric Coefficient of Variation 25.407 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-24, Day 14 | 3012.70 Nanograms×hour per mL | Geometric Coefficient of Variation 19.602 |
| Part A: GSK1292263 800 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-t, Day 14 | 3012.70 Nanograms×hour per mL | Geometric Coefficient of Variation 19.602 |
| Part A: Sitagliptin 100 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-24, Day 14 | 2437.10 Nanograms×hour per mL | Geometric Coefficient of Variation 26.512 |
| Part A: Sitagliptin 100 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-t, Day 14 | 2436.88 Nanograms×hour per mL | Geometric Coefficient of Variation 26.52 |
| Part C: Sitagliptin 100 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-24, Day 14 | 3027.99 Nanograms×hour per mL | Geometric Coefficient of Variation 22.377 |
| Part C: Sitagliptin 100 mg | Part C: Summary of AUC0-24, AUC0-t of GSK1292263 and Sitagliptin When Co-administered | AUC 0-t, Day 14 | 3027.81 Nanograms×hour per mL | Geometric Coefficient of Variation 22.388 |
Secondary
Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered
The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (= immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.
Time frame: Days 1, 7, 13 and 14
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Placebo | Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered | 301.89 Nanograms per mL | Geometric Coefficient of Variation 20.128 |
| Part A: GSK1292263 25 mg | Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered | 284.59 Nanograms per mL | Geometric Coefficient of Variation 20.569 |
| Part A: GSK1292263 150 mg | Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered | 458.24 Nanograms per mL | Geometric Coefficient of Variation 39.382 |
| Part A: GSK1292263 800 mg | Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered | 378.12 Nanograms per mL | Geometric Coefficient of Variation 30.39 |
| Part A: Sitagliptin 100 mg | Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered | 307.45 Nanograms per mL | Geometric Coefficient of Variation 31.323 |
| Part C: Sitagliptin 100 mg | Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered | 360.91 Nanograms per mL | Geometric Coefficient of Variation 26.831 |
Secondary
Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered
The time at which Cmax was observed was determined directly from the raw concentration-time data. The lag time before observation of drug concentrations in sample matrix determined as the time of the sample preceding the first quantifiable concentration. When GSK1292263 was dosed once daily, blood samples were collected on Days 1, 13 and 14 immediately pre-dose (time 0) and at 0.5, 1, 1.5, 2, 3, 4, 6, 8, 14 and 24 hours post-dose. When GSK1292263 was dosed BID, blood samples were collected on Days 1, 13 and 14, at immediately pre-morning dose, 1,2, 4, 6, 8, 10, 11, 12, 14, 16, 18 and 24 hours post-morning dose. For once daily and BID dosing regimens on Day 7, blood samples were collected at pre-dose (= post-breakfast), 1, 2, 4 (= pre-lunch), 6, 10 (= immediately post-dinner) and 12 hours. When planned PK sampling results in multiple samples at the same time point, only one sample was collected.
Time frame: Days 1, 7, 13 and 14
Population: PK Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part A: Placebo | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-half, Day 14 | 7.60 Hour |
| Part A: Placebo | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-max, Day 14 | 2.00 Hour |
| Part A: GSK1292263 25 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-half, Day 14 | 7.24 Hour |
| Part A: GSK1292263 25 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-max, Day 14 | 2.00 Hour |
| Part A: GSK1292263 150 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-half, Day 14 | 7.38 Hour |
| Part A: GSK1292263 150 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-max, Day 14 | 2.00 Hour |
| Part A: GSK1292263 800 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-half, Day 14 | 7.22 Hour |
| Part A: GSK1292263 800 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-max, Day 14 | 2.00 Hour |
| Part A: Sitagliptin 100 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-half, Day 14 | 7.85 Hour |
| Part A: Sitagliptin 100 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-max, Day 14 | 2.00 Hour |
| Part C: Sitagliptin 100 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-half, Day 14 | 7.89 Hour |
| Part C: Sitagliptin 100 mg | Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered | T-max, Day 14 | 2.00 Hour |