Matching placebo to active drug GSK1292263

Sitagliptin (Januvia) 100mg tablets are beige, round, film-coated tablets with "277" on one side.

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).

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).

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.

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.

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.

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.

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.

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.

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).

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).

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.

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.

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.

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.

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.

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.

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.

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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).

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.

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.

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.

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.

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.

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.

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.

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.

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

For additional information about this study please refer to the GSK Clinical Study Register

In this part (Cohort 2), after the appropriate washout period, T2DM participants on monotherapy or sub-maximal anti-diabetic medications were randomized to receive 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 after breakfast and lunch and dinner was approximately 4 and 10 hours after dosing.

Participants were randomized to 14 days of dosing with 4 dose regimens of GSK1292263 (final doses were: 50 mg twice daily [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, pharmacokinetics (PK) and pharmacodynamics (PD) of GSK1292263 when dosed in a BID regimen and vice versa. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 150 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 800 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive sitagliptin 100 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 150 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 800 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive sitagliptin 100 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 800 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive sitagliptin 100 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 800 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive sitagliptin 100 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 800 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 800 mg orally 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.

In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 800 mg orally 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.

Participants were randomized to 14 days of dosing GSK1292263 300 mg BID. 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing GSK1292263 600 mg once daily. 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing with matching placebo (administered BID). 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing with 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing GSK1292263 300 mg BID. 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing GSK1292263 600 mg once daily. 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing with matching placebo (administered BID). 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing with 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing GSK1292263 300 mg BID. 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing GSK1292263 600 mg once daily. 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing with matching placebo (administered BID). 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.

Participants were randomized to 14 days of dosing with 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. For once daily dosing, study drug was administered immediately after breakfast. For BID dosing, study drug was administered immediately after breakfast and immediately after the evening meal, but prior to the 10 hour PK sample.