Trial Outcomes & Findings for A Study in Type 2 Diabetics of Single and Multiple Doses of Orally Administered GSK1292263 to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics (NCT NCT01119846)

NCT ID: NCT01119846

Last Updated: 2018-01-17

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 100 participants
• Primary outcome timeframe: Up to Week 10
• Results posted on: 2018-01-17

Participant Flow

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.

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.

Participant milestones

Measure	Part A In this part (Cohort 1), drug naïve T2DM participants were randomized to receive escalating doses of GSK1292263 25 milligrams (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 oral glucose tolerance test (OGTT).	Part B 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.	Part C 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.
Overall Study STARTED	13	4	83
Overall Study COMPLETED	11	4	72
Overall Study NOT COMPLETED	2	0	11

Reasons for withdrawal

Measure	Part A In this part (Cohort 1), drug naïve T2DM participants were randomized to receive escalating doses of GSK1292263 25 milligrams (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 oral glucose tolerance test (OGTT).	Part B 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.	Part C 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.
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

A Study in Type 2 Diabetics of Single and Multiple Doses of Orally Administered GSK1292263 to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics

Baseline characteristics by cohort

Measure	Part A n=13 Participants 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.	Part B n=4 Participants 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.	Part C n=83 Participants 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.	Total n=100 Participants Total of all reporting groups
Age, Customized 18-60 Years	13 Participants n=5 Participants	4 Participants n=7 Participants	83 Participants n=5 Participants	100 Participants n=4 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	1 Participants n=7 Participants	22 Participants n=5 Participants	27 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	3 Participants n=7 Participants	61 Participants n=5 Participants	73 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	6 Participants n=5 Participants	8 Participants n=4 Participants
Race (NIH/OMB) White	12 Participants n=5 Participants	3 Participants n=7 Participants	75 Participants n=5 Participants	90 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	2 Participants	2 Participants	2 Participants	4 Participants	2 Participants	—
Part A: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Week 10

Population: Safety Population.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Number of Participants With Abnormal Hematology Parameters of Potential Clinical Importance (PCI)	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	—

PRIMARY outcome

Timeframe: Up to Week 10

Population: Safety Population.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI CO2, Low	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—
Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI Magnesium, High	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Part A: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI Glucose, High	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Week 10

Population: Safety Population.

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).

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Number of Participants With Abnormal Electrocardiogram (ECG) Findings	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Week 10.

Population: Safety Population.

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).

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Number of Participants With Abnormal Vital Signs of PCI	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=11 Participants 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part A: Summary of Maximum Plasma Concentration (Cmax)	52.04 Nanograms per milliliters Geometric Coefficient of Variation 17.147	165.62 Nanograms per milliliters Geometric Coefficient of Variation 37.467	379.79 Nanograms per milliliters Geometric Coefficient of Variation 28.171	—	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=11 Participants 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
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 Interval 1.0 to 6.0	3.00 Hour Interval 2.0 to 8.0	3.00 Hour Interval 1.9 to 6.0	—	—	—
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 Interval 0.0 to 1.0	0.00 Hour Interval 0.0 to 0.5	0.00 Hour Interval 0.0 to 0.5	—	—	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=11 Participants 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
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	1684.86 Nanograms×hour per milliliters Geometric Coefficient of Variation 31.009	3985.72 Nanograms×hour per milliliters Geometric Coefficient of Variation 28.449	—	—	—
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	1685.44 Nanograms×hour per milliliters Geometric Coefficient of Variation 31.015	3979.35 Nanograms×hour per milliliters Geometric Coefficient of Variation 27.457	—	—	—

PRIMARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=16 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=14 Participants 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.	Part A: Sitagliptin 100 mg n=15 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
Part C: Number of Participants With AEs and SAEs Any AE	4 Participants	5 Participants	1 Participants	4 Participants	4 Participants	2 Participants
Part C: Number of Participants With AEs and SAEs Any SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=16 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=14 Participants 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.	Part A: Sitagliptin 100 mg n=15 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
Part C: Number of Participants With Abnormal Hematology Parameters of PCI Total neutrophils, Low	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants
Part C: Number of Participants With Abnormal Hematology Parameters of PCI Hematocrit, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Part C: Number of Participants With Abnormal Hematology Parameters of PCI Hemoglobin, High	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	2 Participants

PRIMARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=14 Participants 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.	Part A: Sitagliptin 100 mg n=16 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI Phosphorus inorganic, Low	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI CO2, High	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI Glucose, High	5 Participants	1 Participants	4 Participants	4 Participants	3 Participants	3 Participants
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI CO2, Low	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI Albumin, Low	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI Calcium, Low	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI Potassium, Low	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI ALT, High	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Part C: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI Sodium, Low	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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).

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=14 Participants 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.	Part A: Sitagliptin 100 mg n=16 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
Part C: Number of Participants With Significant ECG Abnormalities	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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).

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=14 Participants 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.	Part A: Sitagliptin 100 mg n=16 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
Part C: Number of Participants With Abnormal Vital Signs of PCI SBP, Low	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Part C: Number of Participants With Abnormal Vital Signs of PCI Pulse rate, High	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Part C: Number of Participants With Abnormal Vital Signs of PCI SBP, High	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	0 Participants

PRIMARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: Pharmacokinetic Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=13 Participants 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part C: Summary of Plasma Cmax Day 7	410.98 Nanograms per millimeter Geometric Coefficient of Variation 25.083	715.01 Nanograms per millimeter Geometric Coefficient of Variation 26.989	1149.32 Nanograms per millimeter Geometric Coefficient of Variation 25.481	813.03 Nanograms per millimeter Geometric Coefficient of Variation 24.578	—	—
Part C: Summary of Plasma Cmax Day 14	438.36 Nanograms per millimeter Geometric Coefficient of Variation 19.487	715.71 Nanograms per millimeter Geometric Coefficient of Variation 30.769	950.52 Nanograms per millimeter Geometric Coefficient of Variation 35.046	772.89 Nanograms per millimeter Geometric Coefficient of Variation 23.019	—	—
Part C: Summary of Plasma Cmax Day 1	219.36 Nanograms per millimeter Geometric Coefficient of Variation 14.140	364.73 Nanograms per millimeter Geometric Coefficient of Variation 29.202	584.32 Nanograms per millimeter Geometric Coefficient of Variation 30.096	721.18 Nanograms per millimeter Geometric Coefficient of Variation 23.346	—	—
Part C: Summary of Plasma Cmax Day 13	433.12 Nanograms per millimeter Geometric Coefficient of Variation 20.372	732.05 Nanograms per millimeter Geometric Coefficient of Variation 29.116	969.19 Nanograms per millimeter Geometric Coefficient of Variation 31.059	831.23 Nanograms per millimeter Geometric Coefficient of Variation 18.373	—	—

PRIMARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: Pharmacokinetic Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=13 Participants 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part C: Summary of T-max and T-lag T-lag, Day 1	0.00 Hour Interval 0.0 to 0.0	0.00 Hour Interval 0.0 to 0.0	0.00 Hour Interval 0.0 to 0.0	0.50 Hour Interval 0.0 to 0.5	—	—
Part C: Summary of T-max and T-lag T-max, Day 1	4.00 Hour Interval 4.0 to 12.0	12.00 Hour Interval 2.0 to 12.0	12.00 Hour Interval 2.0 to 12.0	3.97 Hour Interval 1.5 to 14.0	—	—
Part C: Summary of T-max and T-lag T-max, Day 7	3.97 Hour Interval 2.0 to 12.0	3.97 Hour Interval 0.0 to 12.0	3.97 Hour Interval 0.0 to 12.0	4.0 Hour Interval 4.0 to 6.0	—	—
Part C: Summary of T-max and T-lag T-max, Day 14	4.01 Hour Interval 4.0 to 12.0	3.98 Hour Interval 1.0 to 6.0	3.98 Hour Interval 1.0 to 12.0	3.98 Hour Interval 3.9 to 4.0	—	—
Part C: Summary of T-max and T-lag T-max, Day 13	3.97 Hour Interval 2.0 to 12.0	3.98 Hour Interval 2.0 to 12.0	3.97 Hour Interval 0.0 to 12.0	3.97 Hour Interval 2.0 to 6.0	—	—

PRIMARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: PK Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=13 Participants 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
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	1868.87 Ratio Geometric Coefficient of Variation 24.974	3076.52 Ratio Geometric Coefficient of Variation 23.023	4003.80 Ratio Geometric Coefficient of Variation 27.722	—	—
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	5869.82 Ratio Geometric Coefficient of Variation 32.289	7332.26 Ratio Geometric Coefficient of Variation 32.746	5348.21 Ratio Geometric Coefficient of Variation 22.627	—	—
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	5723.55 Ratio Geometric Coefficient of Variation 32.728	7451.13 Ratio Geometric Coefficient of Variation 37.067	5470.57 Ratio Geometric Coefficient of Variation 23.708	—	—
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	14356.75 Ratio Geometric Coefficient of Variation 29.796	19134.61 Ratio Geometric Coefficient of Variation 34.542	10166.83 Ratio Geometric Coefficient of Variation 26.747	—	—
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	6413.05 Ratio Geometric Coefficient of Variation 31.719	9965.14 Ratio Geometric Coefficient of Variation 27.260	6268.95 Ratio Geometric Coefficient of Variation 27.159	—	—
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	6439.56 Ratio Geometric Coefficient of Variation 26.152	11078.97 Ratio Geometric Coefficient of Variation 24.411	7153.16 Ratio Geometric Coefficient of Variation 34.663	—	—
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	14463.50 Ratio Geometric Coefficient of Variation 29.668	18682.34 Ratio Geometric Coefficient of Variation 32.153	9388.93 Ratio Geometric Coefficient of Variation 26.616	—	—

PRIMARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: PK Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=13 Participants 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part C: Summary of Accumulation Ratio (Ro) Day 14	2.29 Ratio Geometric Coefficient of Variation 19.681	2.15 Ratio Geometric Coefficient of Variation 20.319	1.77 Ratio Geometric Coefficient of Variation 31.510	1.39 Ratio Geometric Coefficient of Variation 39.448	—	—
Part C: Summary of Accumulation Ratio (Ro) Day 13	2.22 Ratio Geometric Coefficient of Variation 21.131	2.17 Ratio Geometric Coefficient of Variation 19.972	1.72 Ratio Geometric Coefficient of Variation 31.647	1.29 Ratio Geometric Coefficient of Variation 40.690	—	—

PRIMARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: PK Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part C: Summary of Time Invariance Ratio (Rs) of AUC0-10 for BID Dose of GSK1292263	2.8174 Ratio Interval 2.5262 to 3.1422	3.0033 Ratio Interval 2.6743 to 3.3727	2.4218 Ratio Interval 2.0455 to 2.8673	—	—	—

PRIMARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: PK Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part C: Summary of Time Invariance Ratio (Rs) of AUC0-24 for Once Daily Dose of GSK1292263	1.2871 Ratio Interval 1.0392 to 1.5941	—	—	—	—	—

PRIMARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: PK Population.

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.

Outcome measures

Measure	Part A: Placebo n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=13 Participants 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part C: Summary of Time Invariance Ratio (Rs) of Cmax	1.9186 Ratio Interval 1.6979 to 2.168	1.6755 Ratio Interval 1.4769 to 1.9007	1.1703 Ratio Interval 1.0414 to 1.3152	—	—	—

PRIMARY outcome

Timeframe: 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.

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).

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=12 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Relationships Between GSK1292263 Drug Exposures and Insulin Sensitivity	1.4 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 98	2.1 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 67	2.3 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 51	2.8 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 86	2.7 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 86	—

PRIMARY outcome

Timeframe: Day -1, 13 and 14

Population: PK/PD Population.

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).

Outcome measures

Measure	Part A: Placebo n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=12 Participants 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.	Part A: Sitagliptin 100 mg n=12 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
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	8.6 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 50	8.7 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 99	7.2 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 72	6.6 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 59	7.4 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 122
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	9.0 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 52	7.3 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 90	8.0 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 75	6.8 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 91	5.7 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 124
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	9.8 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 100	9.2 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 80	8.0 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 96	6.6 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 79	7.0 mL/min×1/µIU×10^4 Geometric Coefficient of Variation 107

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Summary of Change From Baseline in Fasted Glucose	0.52 Millimoles per Liter Geometric Coefficient of Variation 795.822	1.49 Millimoles per Liter Geometric Coefficient of Variation 848.906	0.53 Millimoles per Liter Geometric Coefficient of Variation 533.024	0.87 Millimoles per Liter Geometric Coefficient of Variation 653.005	0.58 Millimoles per Liter Geometric Coefficient of Variation -220.270	—

PRIMARY outcome

Timeframe: Up to Day 1 (24 hours)

Population: PD Population.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
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	1.35 Millimoles per Liter Geometric Coefficient of Variation 62.815	1.48 Millimoles per Liter Geometric Coefficient of Variation 59.021	1.78 Millimoles per Liter Geometric Coefficient of Variation 64.653	1.48 Millimoles per Liter Geometric Coefficient of Variation 97.908	—
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	1.04 Millimoles per Liter Geometric Coefficient of Variation 96.395	1.44 Millimoles per Liter Geometric Coefficient of Variation 137.548	0.90 Millimoles per Liter Geometric Coefficient of Variation 141.078	0.53 Millimoles per Liter Geometric Coefficient of Variation 188.368	—
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	9.44 Millimoles per Liter Geometric Coefficient of Variation 24.357	9.15 Millimoles per Liter Geometric Coefficient of Variation 21.389	8.64 Millimoles per Liter Geometric Coefficient of Variation 20.241	9.23 Millimoles per Liter Geometric Coefficient of Variation 39.431	—
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	9.17 Millimoles per Liter Geometric Coefficient of Variation 22.684	9.03 Millimoles per Liter Geometric Coefficient of Variation 20.928	8.67 Millimoles per Liter Geometric Coefficient of Variation 18.128	8.95 Millimoles per Liter Geometric Coefficient of Variation 33.715	—

PRIMARY outcome

Timeframe: Up to Day 1 (24 hours)

Population: PD Population.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
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	1518.81 Pico moles per Liter Geometric Coefficient of Variation 31.728	1523.99 Pico moles per Liter Geometric Coefficient of Variation 26.370	1513.90 Pico moles per Liter Geometric Coefficient of Variation 23.322	1418.12 Pico moles per Liter Geometric Coefficient of Variation 31.849	—
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	874.41 Pico moles per Liter Geometric Coefficient of Variation 39.842	821.46 Pico moles per Liter Geometric Coefficient of Variation 34.785	846.34 Pico moles per Liter Geometric Coefficient of Variation 29.692	836.98 Pico moles per Liter Geometric Coefficient of Variation 35.373	—
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	0.06 Pico moles per Liter Geometric Coefficient of Variation 346.410	0.12 Pico moles per Liter Geometric Coefficient of Variation 153.295	0.07 Pico moles per Liter Geometric Coefficient of Variation 191.029	3.05 Pico moles per Liter Geometric Coefficient of Variation 50.439	—
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	5.83 Pico moles per Liter Geometric Coefficient of Variation 41.037	6.13 Pico moles per Liter Geometric Coefficient of Variation 29.049	7.44 Pico moles per Liter Geometric Coefficient of Variation 39.162	4.04 Pico moles per Liter Geometric Coefficient of Variation 39.915	—
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	3.34 Pico moles per Liter Geometric Coefficient of Variation 57.021	3.64 Pico moles per Liter Geometric Coefficient of Variation 42.846	4.33 Pico moles per Liter Geometric Coefficient of Variation 41.068	2.36 Pico moles per Liter Geometric Coefficient of Variation 71.247	—
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	9.55 Pico moles per Liter Geometric Coefficient of Variation 39.783	10.62 Pico moles per Liter Geometric Coefficient of Variation 37.541	9.34 Pico moles per Liter Geometric Coefficient of Variation 52.831	7.44 Pico moles per Liter Geometric Coefficient of Variation 37.297	—
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	2.81 Pico moles per Liter Geometric Coefficient of Variation 194.661	2.60 Pico moles per Liter Geometric Coefficient of Variation 148.080	1.97 Pico moles per Liter Geometric Coefficient of Variation 83.805	1.86 Pico moles per Liter Geometric Coefficient of Variation 50.802	—
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	272.04 Pico moles per Liter Geometric Coefficient of Variation 45.425	277.10 Pico moles per Liter Geometric Coefficient of Variation 53.966	280.90 Pico moles per Liter Geometric Coefficient of Variation 46.494	210.66 Pico moles per Liter Geometric Coefficient of Variation 48.374	—
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	29.72 Pico moles per Liter Geometric Coefficient of Variation 26.567	30.46 Pico moles per Liter Geometric Coefficient of Variation 34.393	35.38 Pico moles per Liter Geometric Coefficient of Variation 34.413	17.67 Pico moles per Liter Geometric Coefficient of Variation 32.393	—
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	15.04 Pico moles per Liter Geometric Coefficient of Variation 38.723	15.56 Pico moles per Liter Geometric Coefficient of Variation 54.028	17.74 Pico moles per Liter Geometric Coefficient of Variation 43.836	3.79 Pico moles per Liter Geometric Coefficient of Variation 105.916	—
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	44.91 Pico moles per Liter Geometric Coefficient of Variation 28.596	44.07 Pico moles per Liter Geometric Coefficient of Variation 26.903	51.21 Pico moles per Liter Geometric Coefficient of Variation 26.338	32.76 Pico moles per Liter Geometric Coefficient of Variation 28.341	—
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	38.77 Pico moles per Liter Geometric Coefficient of Variation 29.579	38.52 Pico moles per Liter Geometric Coefficient of Variation 28.757	42.15 Pico moles per Liter Geometric Coefficient of Variation 24.080	28.03 Pico moles per Liter Geometric Coefficient of Variation 31.909	—
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	2.12 Pico moles per Liter Geometric Coefficient of Variation 0.815	2.26 Pico moles per Liter Geometric Coefficient of Variation 10.182	2.20 Pico moles per Liter Geometric Coefficient of Variation 7.629	5.35 Pico moles per Liter Geometric Coefficient of Variation 30.858	—
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	199.42 Pico moles per Liter Geometric Coefficient of Variation 46.245	207.02 Pico moles per Liter Geometric Coefficient of Variation 55.393	208.19 Pico moles per Liter Geometric Coefficient of Variation 50.315	151.53 Pico moles per Liter Geometric Coefficient of Variation 51.789	—

PRIMARY outcome

Timeframe: Up to Day 1 (24 hours)

Population: PD Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
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 14.080	12.79 Millimoles per Liter Geometric Coefficient of Variation 18.904	12.12 Millimoles per Liter Geometric Coefficient of Variation 16.572	11.26 Millimoles per Liter Geometric Coefficient of Variation 16.651	11.97 Millimoles per Liter Geometric Coefficient of Variation 25.950	—
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	5.17 Millimoles per Liter Geometric Coefficient of Variation 19.811	4.78 Millimoles per Liter Geometric Coefficient of Variation 20.419	4.25 Millimoles per Liter Geometric Coefficient of Variation 27.727	4.43 Millimoles per Liter Geometric Coefficient of Variation 28.677	—

PRIMARY outcome

Timeframe: Up to Day 1 (24 hours)

Population: PD Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
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	230.91 Pico moles per Liter Geometric Coefficient of Variation 39.743	235.88 Pico moles per Liter Geometric Coefficient of Variation 42.743	254.61 Pico moles per Liter Geometric Coefficient of Variation 50.810	213.17 Pico moles per Liter Geometric Coefficient of Variation 49.480	—
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	156.32 Pico moles per Liter Geometric Coefficient of Variation 41.131	161.05 Pico moles per Liter Geometric Coefficient of Variation 45.743	179.93 Pico moles per Liter Geometric Coefficient of Variation 58.350	150.33 Pico moles per Liter Geometric Coefficient of Variation 56.399	—
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	19.30 Pico moles per Liter Geometric Coefficient of Variation 42.059	22.45 Pico moles per Liter Geometric Coefficient of Variation 39.164	23.42 Pico moles per Liter Geometric Coefficient of Variation 25.206	13.93 Pico moles per Liter Geometric Coefficient of Variation 35.971	—
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	4.66 Pico moles per Liter Geometric Coefficient of Variation 95.556	6.81 Pico moles per Liter Geometric Coefficient of Variation 74.605	5.59 Pico moles per Liter Geometric Coefficient of Variation 62.823	1.25 Pico moles per Liter Geometric Coefficient of Variation 162.044	—
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	676.24 Pico moles per Liter Geometric Coefficient of Variation 40.442	620.95 Pico moles per Liter Geometric Coefficient of Variation 41.762	695.31 Pico moles per Liter Geometric Coefficient of Variation 43.060	692.11 Pico moles per Liter Geometric Coefficient of Variation 45.456	—
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	37.86 Pico moles per Liter Geometric Coefficient of Variation 26.719	34.82 Pico moles per Liter Geometric Coefficient of Variation 34.834	42.25 Pico moles per Liter Geometric Coefficient of Variation 34.507	26.57 Pico moles per Liter Geometric Coefficient of Variation 40.429	—
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	2.12 Pico moles per Liter Geometric Coefficient of Variation 0.000	2.18 Pico moles per Liter Geometric Coefficient of Variation 4.606	2.14 Pico moles per Liter Geometric Coefficient of Variation 2.540	4.73 Pico moles per Liter Geometric Coefficient of Variation 22.230	—
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	NA Pico moles per Liter Geometric Coefficient of Variation NA NA indicates data not evaluable.	0.18 Pico moles per Liter Geometric Coefficient of Variation 158.801	0.18 Pico moles per Liter Geometric Coefficient of Variation 331.662	2.47 Pico moles per Liter Geometric Coefficient of Variation 38.584	—
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	0.24 Pico moles per Liter Geometric Coefficient of Variation -157.518	0.62 Pico moles per Liter Geometric Coefficient of Variation -157.616	0.73 Pico moles per Liter Geometric Coefficient of Variation -122.368	0.39 Pico moles per Liter Geometric Coefficient of Variation -121.494	—
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	1352.32 Pico moles per Liter Geometric Coefficient of Variation 28.098	1357.81 Pico moles per Liter Geometric Coefficient of Variation 20.421	1387.78 Pico moles per Liter Geometric Coefficient of Variation 25.473	1287.66 Pico moles per Liter Geometric Coefficient of Variation 34.527	—
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	31.50 Pico moles per Liter Geometric Coefficient of Variation 30.146	29.27 Pico moles per Liter Geometric Coefficient of Variation 37.728	33.51 Pico moles per Liter Geometric Coefficient of Variation 29.808	21.79 Pico moles per Liter Geometric Coefficient of Variation 45.161	—
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	4.51 Pico moles per Liter Geometric Coefficient of Variation 36.731	5.02 Pico moles per Liter Geometric Coefficient of Variation 27.985	5.59 Pico moles per Liter Geometric Coefficient of Variation 37.459	2.97 Pico moles per Liter Geometric Coefficient of Variation 34.891	—
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	1.66 Pico moles per Liter Geometric Coefficient of Variation 80.669	2.40 Pico moles per Liter Geometric Coefficient of Variation 51.939	2.38 Pico moles per Liter Geometric Coefficient of Variation 49.604	1.26 Pico moles per Liter Geometric Coefficient of Variation 63.785	—
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	4.77 Pico moles per Liter Geometric Coefficient of Variation 40.537	6.08 Pico moles per Liter Geometric Coefficient of Variation 39.006	4.49 Pico moles per Liter Geometric Coefficient of Variation 44.216	3.85 Pico moles per Liter Geometric Coefficient of Variation 62.260	—

PRIMARY outcome

Timeframe: Up to Day 1 (24 hours)

Population: PD Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Summary of the OGTT Derived Parameters: Disposition Index	0.87 [(µIU/mL)/(mg/deciliter [dL])]^2 Geometric Coefficient of Variation 201.883	0.76 [(µIU/mL)/(mg/deciliter [dL])]^2 Geometric Coefficient of Variation 65.975	1.07 [(µIU/mL)/(mg/deciliter [dL])]^2 Geometric Coefficient of Variation 78.991	0.94 [(µIU/mL)/(mg/deciliter [dL])]^2 Geometric Coefficient of Variation 62.371	0.86 [(µIU/mL)/(mg/deciliter [dL])]^2 Geometric Coefficient of Variation 95.526	—

PRIMARY outcome

Timeframe: Up to Day 1 (24 hours)

Population: PD Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
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	0.06 Ratio Geometric Coefficient of Variation 73.172	0.05 Ratio Geometric Coefficient of Variation 61.602	0.04 Ratio Geometric Coefficient of Variation 56.203	0.06 Ratio Geometric Coefficient of Variation 154.204	—
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	18.05 Ratio Geometric Coefficient of Variation 40.272	19.46 Ratio Geometric Coefficient of Variation 50.494	22.61 Ratio Geometric Coefficient of Variation 60.152	17.80 Ratio Geometric Coefficient of Variation 54.449	—

PRIMARY outcome

Timeframe: Up to Day 1 (24 hours)

Population: PD Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
Part A: Summary of the OGTT Derived Parameters: Insulin Glucose Index	0.23 µIU/mL/mg/dL Geometric Coefficient of Variation 144.722	0.22 µIU/mL/mg/dL Geometric Coefficient of Variation 54.340	0.28 µIU/mL/mg/dL Geometric Coefficient of Variation 67.645	0.26 µIU/mL/mg/dL Geometric Coefficient of Variation 64.622	0.21 µIU/mL/mg/dL Geometric Coefficient of Variation 75.325	—

PRIMARY outcome

Timeframe: Up to Day 1 (24 hours)

Population: PD Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=11 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=11 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg 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.
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	3.47 1/(mg/dL)×1/(µIU/mL) Geometric Coefficient of Variation 45.993	3.87 1/(mg/dL)×1/(µIU/mL) Geometric Coefficient of Variation 42.720	3.60 1/(mg/dL)×1/(µIU/mL) Geometric Coefficient of Variation 37.292	4.01 1/(mg/dL)×1/(µIU/mL) Geometric Coefficient of Variation 47.046	—

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=12 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
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	4.93 Millimoles per Liter Geometric Coefficient of Variation 41.905	7.39 Millimoles per Liter Geometric Coefficient of Variation 36.730	5.17 Millimoles per Liter Geometric Coefficient of Variation 57.754	5.51 Millimoles per Liter Geometric Coefficient of Variation 38.497	4.09 Millimoles per Liter Geometric Coefficient of Variation 70.342
Part C: Summary of Change From Baseline in Fasted Glucose Day 7, 2 Hours	4.71 Millimoles per Liter Geometric Coefficient of Variation 150.720	3.65 Millimoles per Liter Geometric Coefficient of Variation 82.667	5.00 Millimoles per Liter Geometric Coefficient of Variation 45.953	3.61 Millimoles per Liter Geometric Coefficient of Variation 75.258	2.59 Millimoles per Liter Geometric Coefficient of Variation 60.658	3.17 Millimoles per Liter Geometric Coefficient of Variation 152.623
Part C: Summary of Change From Baseline in Fasted Glucose Day 7, 4 Hours	1.85 Millimoles per Liter Geometric Coefficient of Variation -482.690	1.11 Millimoles per Liter Geometric Coefficient of Variation -606.064	1.13 Millimoles per Liter Geometric Coefficient of Variation 270.863	2.05 Millimoles per Liter Geometric Coefficient of Variation 685.731	0.95 Millimoles per Liter Geometric Coefficient of Variation -223.367	2.13 Millimoles per Liter Geometric Coefficient of Variation -188.101
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	3.72 Millimoles per Liter Geometric Coefficient of Variation 67.064	6.16 Millimoles per Liter Geometric Coefficient of Variation 51.414	4.15 Millimoles per Liter Geometric Coefficient of Variation 74.614	3.93 Millimoles per Liter Geometric Coefficient of Variation 62.647	3.70 Millimoles per Liter Geometric Coefficient of Variation 270.326
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	1.91 Millimoles per Liter Geometric Coefficient of Variation 166.934	3.18 Millimoles per Liter Geometric Coefficient of Variation 83.271	3.13 Millimoles per Liter Geometric Coefficient of Variation 133.236	2.06 Millimoles per Liter Geometric Coefficient of Variation 228.901	5.17 Millimoles per Liter Geometric Coefficient of Variation -1115.737
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	2.42 Millimoles per Liter Geometric Coefficient of Variation 71.838	4.41 Millimoles per Liter Geometric Coefficient of Variation 49.106	3.53 Millimoles per Liter Geometric Coefficient of Variation 82.377	3.77 Millimoles per Liter Geometric Coefficient of Variation 60.670	3.33 Millimoles per Liter Geometric Coefficient of Variation 119.827
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	1.09 Millimoles per Liter Geometric Coefficient of Variation 3884.234	1.34 Millimoles per Liter Geometric Coefficient of Variation 179.562	1.21 Millimoles per Liter Geometric Coefficient of Variation 2819.220	1.52 Millimoles per Liter Geometric Coefficient of Variation 565.287	2.08 Millimoles per Liter Geometric Coefficient of Variation -323.555

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=12 Participants 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.	Part A: Sitagliptin 100 mg n=13 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
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	117.15 Millimoles per Liter Geometric Coefficient of Variation 53.056	151.56 Millimoles per Liter Geometric Coefficient of Variation 88.163	129.44 Millimoles per Liter Geometric Coefficient of Variation 101.186	216.95 Millimoles per Liter Geometric Coefficient of Variation 91.593	162.83 Millimoles per Liter Geometric Coefficient of Variation 62.028
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	94.18 Millimoles per Liter Geometric Coefficient of Variation 55.907	143.75 Millimoles per Liter Geometric Coefficient of Variation 108.953	87.30 Millimoles per Liter Geometric Coefficient of Variation 145.016	160.57 Millimoles per Liter Geometric Coefficient of Variation 123.482	163.46 Millimoles per Liter Geometric Coefficient of Variation 80.530
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	95.16 Millimoles per Liter Geometric Coefficient of Variation 69.323	98.26 Millimoles per Liter Geometric Coefficient of Variation 140.843	114.93 Millimoles per Liter Geometric Coefficient of Variation 81.742	138.42 Millimoles per Liter Geometric Coefficient of Variation 54.450	123.65 Millimoles per Liter Geometric Coefficient of Variation 74.446
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	1.51 Millimoles per Liter Geometric Coefficient of Variation -256.494	3.54 Millimoles per Liter Geometric Coefficient of Variation -116.769	11.03 Millimoles per Liter Geometric Coefficient of Variation -226.913	7.87 Millimoles per Liter Geometric Coefficient of Variation -322.274	3.26 Millimoles per Liter Geometric Coefficient of Variation -191.100
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	20.10 Millimoles per Liter Geometric Coefficient of Variation 354.147	27.32 Millimoles per Liter Geometric Coefficient of Variation 97.622	21.93 Millimoles per Liter Geometric Coefficient of Variation 337.965	19.41 Millimoles per Liter Geometric Coefficient of Variation 150.506	30.25 Millimoles per Liter Geometric Coefficient of Variation 169.388
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	88.70 Millimoles per Liter Geometric Coefficient of Variation 70.484	136.15 Millimoles per Liter Geometric Coefficient of Variation 92.906	131.08 Millimoles per Liter Geometric Coefficient of Variation 84.834	142.10 Millimoles per Liter Geometric Coefficient of Variation 74.418	130.88 Millimoles per Liter Geometric Coefficient of Variation 48.541
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	55.28 Millimoles per Liter Geometric Coefficient of Variation 131.603	55.40 Millimoles per Liter Geometric Coefficient of Variation 86.768	66.90 Millimoles per Liter Geometric Coefficient of Variation 162.220	64.04 Millimoles per Liter Geometric Coefficient of Variation 72.943	39.35 Millimoles per Liter Geometric Coefficient of Variation 76.204

SECONDARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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.

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Number of Participants With AEs and SAEs Any AE	0 Participants	1 Participants	—	—	—	—
Part B: Number of Participants With AEs and SAEs Any SAE	0 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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.

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Number of Participants With Abnormal Hematology Parameters of PCI	0 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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.

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Number of Participants With Abnormal Clinical Chemistry Parameters of PCI	1 Participants	1 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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).

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Number of Participants With Significant ECG Abnormalities	0 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: Up to Week 7

Population: Safety Population.

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).

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Number of Participants With Abnormal Vital Signs of PCI	0 Participants	0 Participants	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Summary of Plasma Cmax	339.52 Nanograms per mL Geometric Coefficient of Variation 32.581	944.21 Nanograms per mL Geometric Coefficient of Variation 47.330	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Summary of T-max and T-lag T-max	2.00 Hour Interval 2.0 to 4.0	4.98 Hour Interval 4.0 to 13.1	—	—	—	—
Part B: Summary of T-max and T-lag T-lag	0.00 Hour Interval 0.0 to 0.5	0.00 Hour Interval 0.0 to 0.0	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Summary of AUC0-t and AUC0-24 AUC 0-t	3370.43 Nanograms×hour per mL Geometric Coefficient of Variation 21.507	12659.88 Nanograms×hour per mL Geometric Coefficient of Variation 27.391	—	—	—	—
Part B: Summary of AUC0-t and AUC0-24 AUC 0-24	3370.43 Nanograms×hour per mL Geometric Coefficient of Variation 21.507	12639.84 Nanograms×hour per mL Geometric Coefficient of Variation 27.622	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
Part B: Summary of Change From Baseline in Fasted Glucose	0.40 Millimoles per Liter Geometric Coefficient of Variation 62.025	1.95 Millimoles per Liter Geometric Coefficient of Variation -10966.01	—	—	—	—

SECONDARY outcome

Timeframe: Baseline (Day 1 pre-dose) and Day 1 (24 hours)

Population: PD Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=4 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg 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.	Part A: GSK1292263 800 mg 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.	Part A: Sitagliptin 100 mg 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.	Part C: Sitagliptin 100 mg 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.
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	55.83 Pico moles per Liter Geometric Coefficient of Variation -507.439	—	—	—	—
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 Geometric Coefficient of Variation NA NA indicates: The mean change from Baseline is 0.00, hence measure dispersion could not be calculated.	0.00 Pico moles per Liter Geometric Coefficient of Variation NA NA indicates: The mean change from Baseline is 0.00, hence measure dispersion could not be calculated.	—	—	—	—
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	5.40 Pico moles per Liter Geometric Coefficient of Variation -165.542	—	—	—	—
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 384.900	0.48 Pico moles per Liter Geometric Coefficient of Variation 66.682	—	—	—	—
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 Geometric Coefficient of Variation NA NA signifies measure dispersion was not calculated as only one participant was available.	2.02 Pico moles per Liter Geometric Coefficient of Variation 72.451	—	—	—	—
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	7.19 Pico moles per Liter Geometric Coefficient of Variation 7682.607	—	—	—	—
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	4.55 Pico moles per Liter Geometric Coefficient of Variation 181.246	—	—	—	—

SECONDARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: PK Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=12 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=11 Participants 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.	Part A: GSK1292263 800 mg n=10 Participants 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.	Part A: Sitagliptin 100 mg n=12 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
Part C: Summary of Cmax of GSK1292263 and Sitagliptin When Co-administered	301.89 Nanograms per mL Geometric Coefficient of Variation 20.128	284.59 Nanograms per mL Geometric Coefficient of Variation 20.569	458.24 Nanograms per mL Geometric Coefficient of Variation 39.382	378.12 Nanograms per mL Geometric Coefficient of Variation 30.390	307.45 Nanograms per mL Geometric Coefficient of Variation 31.323	360.91 Nanograms per mL Geometric Coefficient of Variation 26.831

SECONDARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: PK Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=13 Participants 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.	Part A: Sitagliptin 100 mg n=12 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered T-half, Day 14	7.60 Hour Interval 6.3 to 10.4	7.24 Hour Interval 6.2 to 9.1	7.38 Hour Interval 5.9 to 8.1	7.22 Hour Interval 4.9 to 9.1	7.85 Hour Interval 6.3 to 8.9	7.89 Hour Interval 7.1 to 9.7
Part C: Summary of T-half and Tmax of GSK1292263 and Sitagliptin When Co-administered T-max, Day 14	2.00 Hour Interval 1.0 to 4.0	2.00 Hour Interval 2.0 to 4.0	2.00 Hour Interval 1.0 to 4.0	2.00 Hour Interval 0.5 to 3.0	2.00 Hour Interval 1.0 to 4.0	2.00 Hour Interval 0.5 to 4.0

SECONDARY outcome

Timeframe: Days 1, 7, 13 and 14

Population: PK Population. Only those participants available at the specified time points were analyzed.

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.

Outcome measures

Measure	Part A: Placebo n=14 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive placebo 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.	Part A: GSK1292263 25 mg n=15 Participants In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg n=12 Participants 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.	Part A: GSK1292263 800 mg n=13 Participants 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.	Part A: Sitagliptin 100 mg n=12 Participants 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.	Part C: Sitagliptin 100 mg n=12 Participants 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.
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	2585.15 Nanograms×hour per mL Geometric Coefficient of Variation 18.942	3338.49 Nanograms×hour per mL Geometric Coefficient of Variation 25.396	3012.70 Nanograms×hour per mL Geometric Coefficient of Variation 19.602	2437.10 Nanograms×hour per mL Geometric Coefficient of Variation 26.512	3027.99 Nanograms×hour per mL Geometric Coefficient of Variation 22.377
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	2585.10 Nanograms×hour per mL Geometric Coefficient of Variation 18.944	3338.27 Nanograms×hour per mL Geometric Coefficient of Variation 25.407	3012.70 Nanograms×hour per mL Geometric Coefficient of Variation 19.602	2436.88 Nanograms×hour per mL Geometric Coefficient of Variation 26.520	3027.81 Nanograms×hour per mL Geometric Coefficient of Variation 22.388

Adverse Events

Part A: Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: GSK1292263 25 mg Orally

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: GSK1292263 150 mg Orally

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part A: GSK1292263 800 mg Orally

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part A: Sitagliptin 100 mg Orally

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B: GSK1292263 800 mg Fasted Condition Orally

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part B: GSK1292263 800 mg Fed Condition Orally

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part C: GSK1292263 50 mg BID Orally

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part C: GSK1292263 150 mg BID Orally

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Part C: GSK1292263 300 mg BID Orally

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Part C: GSK1292263 600 mg Once Daily Orally

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part C: Placebo Orally

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Part C: Sitagliptin 100 mg Once Daily Orally

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Part A: Placebo n=11 participants at risk In this part (Cohort 1), drug naïve T2DM participants were randomized to receive matching placebo 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.	Part A: GSK1292263 25 mg Orally n=12 participants at risk In this part (Cohort 1), drug naïve T2DM participants were randomized to receive GSK1292263 25 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.	Part A: GSK1292263 150 mg Orally n=12 participants at risk 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.	Part A: GSK1292263 800 mg Orally n=11 participants at risk 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.	Part A: Sitagliptin 100 mg Orally n=13 participants at risk 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.	Part B: GSK1292263 800 mg Fasted Condition Orally n=4 participants at risk 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 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 min after breakfast and lunch and dinner was approximately 4 and 10 hours after dosing.	Part B: GSK1292263 800 mg Fed Condition Orally n=4 participants at risk 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 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 min after breakfast and lunch and dinner was approximately 4 and 10 hours after dosing.	Part C: GSK1292263 50 mg BID Orally n=14 participants at risk Participants were randomized to 14 days of dosing with GSK1292263 50 mg BID 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.	Part C: GSK1292263 150 mg BID Orally n=16 participants at risk Participants were randomized to 14 days of dosing with GSK1292263 150 mg BID 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.	Part C: GSK1292263 300 mg BID Orally n=12 participants at risk 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.	Part C: GSK1292263 600 mg Once Daily Orally n=14 participants at risk 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.	Part C: Placebo Orally n=15 participants at risk 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.	Part C: Sitagliptin 100 mg Once Daily Orally n=12 participants at risk 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.
Blood and lymphatic system disorders Iron deficiency	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Nervous system disorders Headache	18.2% 2/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	18.2% 2/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	25.0% 1/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	13.3% 2/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Nervous system disorders Dizziness	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	16.7% 2/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	9.1% 1/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Eye disorders Vision blurred	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	9.1% 1/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.7% 1/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
General disorders Chest pain	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
General disorders Fatigue	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Gastrointestinal disorders Constipation	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	12.5% 2/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Gastrointestinal disorders Vomiting	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	13.3% 2/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Gastrointestinal disorders Diarrhoea	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	13.3% 2/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Gastrointestinal disorders Nausea	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	13.3% 2/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Gastrointestinal disorders Abdominal pain	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.7% 1/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Gastrointestinal disorders Dyspepsia	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Gastrointestinal disorders Flatulence	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
General disorders Chills	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.7% 1/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
General disorders Oedema peripheral	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
General disorders Pain	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
General disorders Pyrexia	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.7% 1/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	14.3% 2/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	12.5% 2/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Infections and infestations Upper respiratory tract infection	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Infections and infestations Rhinitis	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Injury, poisoning and procedural complications Fall	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.7% 1/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Injury, poisoning and procedural complications Tooth fracture	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	6.2% 1/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	7.1% 1/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Renal and urinary disorders Dysuria	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Respiratory, thoracic and mediastinal disorders Throat irritation	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.
Skin and subcutaneous tissue disorders Rash erythematous	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/11 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/13 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/4 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/16 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/14 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	0.00% 0/15 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.	8.3% 1/12 • AEs and SAEs were reported throughout the study (approximately up to Week 62). ITT analysis set was used for reporting AE and SAE.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.
• Publication restrictions are in place

Restriction type: OTHER