Trial Outcomes & Findings for A Study in Type 2 Diabetic Subjects on Stable Metformin Therapy to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Co-administering Single and Multiple Oral Doses of GSK1292263 (NCT NCT01128621)

Results Overview

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

66 participants

Primary outcome timeframe

Up to 10 days after discharge (Day 2) in Part A

Results posted on

2017-10-16

Participant Flow

The study was conducted at two study centers in the United States from 23 November 2009 up to 12 April 2010. The study consisted of open label Part A and single-blind Part B. Total 6 participants were randomized in Part A whereas total 67 participants were randomized in Part B.

Participant milestones

Participant milestones
Measure	Part A: GSK1292263 300 mg Participants received a single dose of oral 300 milligrams (mg) tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	Part B: GSK1292263 75 mg/300 mg/ 600 mg Participants received one of three dosing regimens of GSK1292263: 75 mg twice daily (BID) (as 1 x 75 mg tablet GSK1292263 + 2 placebo tablets in morning and evening), 300 mg BID (as 1 x 200 mg tablet + 1 x 75 mg tablet + 1 x 25 mg tablet GSK1292263 in morning and evening) and 600 mg once daily (QD) (as 3 x 200 mg tablets GSK1292263 in morning + 3 x placebo tablets in evening) or matching placebo BID (as 3 x placebo tablets in morning and evening), or open-label sitagliptin 50 mg BID for 14 days. Seven days before enrollment in Part B, participants taking metformin three times daily (TID) or using an extended-release formulation were converted to the equivalent total daily dose of immediate release metformin administered BID.
Part A: GSK1292263 300 mg STARTED	6	0
Part A: GSK1292263 300 mg COMPLETED	6	0
Part A: GSK1292263 300 mg NOT COMPLETED	0	0
Part B: GSK1292263 75 mg/300 mg/ 600 mg STARTED	0	67
Part B: GSK1292263 75 mg/300 mg/ 600 mg COMPLETED	0	65
Part B: GSK1292263 75 mg/300 mg/ 600 mg NOT COMPLETED	0	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Part A: GSK1292263 300 mg Participants received a single dose of oral 300 milligrams (mg) tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	Part B: GSK1292263 75 mg/300 mg/ 600 mg Participants received one of three dosing regimens of GSK1292263: 75 mg twice daily (BID) (as 1 x 75 mg tablet GSK1292263 + 2 placebo tablets in morning and evening), 300 mg BID (as 1 x 200 mg tablet + 1 x 75 mg tablet + 1 x 25 mg tablet GSK1292263 in morning and evening) and 600 mg once daily (QD) (as 3 x 200 mg tablets GSK1292263 in morning + 3 x placebo tablets in evening) or matching placebo BID (as 3 x placebo tablets in morning and evening), or open-label sitagliptin 50 mg BID for 14 days. Seven days before enrollment in Part B, participants taking metformin three times daily (TID) or using an extended-release formulation were converted to the equivalent total daily dose of immediate release metformin administered BID.
Part B: GSK1292263 75 mg/300 mg/ 600 mg Reached defined stopping criteria	0	2

Baseline Characteristics

A Study in Type 2 Diabetic Subjects on Stable Metformin Therapy to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Co-administering Single and Multiple Oral Doses of GSK1292263

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part A: GSK1292263 300 mg n=6 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	Part B: GSK1292263 75 mg/300 mg/ 600 mg n=67 Participants Participants received one of three dosing regimens of GSK1292263: 75 mg twice daily (BID) (as 1 x 75 mg tablet GSK1292263 + 2 placebo tablets in morning and evening), 300 mg BID (as 1 x 200 mg tablet + 1 x 75 mg tablet + 1 x 25 mg tablet GSK1292263 in morning and evening) and 600 mg once daily (QD) (as 3 x 200 mg tablets GSK1292263 in morning + 3 x placebo tablets in evening) or matching placebo BID (as 3 x placebo tablets in morning and evening), or open-label sitagliptin 50 mg BID for 14 days. Seven days before enrollment in Part B, participants taking metformin three times daily (TID) or using an extended-release formulation were converted to the equivalent total daily dose of immediate release metformin administered BID.	Total n=73 Participants Total of all reporting groups
Age, Customized 36 to 65 Years	6 Participants n=5 Participants	67 Participants n=7 Participants	73 Participants n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	28 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	39 Participants n=7 Participants	44 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	6 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	61 Participants n=7 Participants	65 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population consisted of all participants enrolled in the study and who had received at least one dose of study drug.

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Outcome measures

Outcome measures
Measure	Part A n=6 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (Part A) Any AE	0 Participants	—	—	—	—
Number of Participants With Any Adverse Events (AEs) and Serious Adverse Events (SAEs) (Part A) Any SAE	0 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

Population: Safety Population

An AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) Any AE	2 Participants	3 Participants	3 Participants	4 Participants	5 Participants
Number of Participants With Any AEs and Serious Adverse Events SAEs (Part B) Any SAE	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population

Blood samples for hematology assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Hematology parameter: Total Neutrophil count was assessed for abnormal value of PCI. The range of PCI value was: \<0.83 x lower limit normal (LLN) with unit x10\^9 per liter

Outcome measures

Outcome measures
Measure	Part A n=6 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Hematology Values of Potential Clinical Importance (PCI) (Part A)	1 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

Population: Safety Population

Blood samples for hematology assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Hematology parameters: Hematocrit (unit: ratio) and hemoglobin (unit: grams per liter \[g/L\]), were assessed for abnormal values of PCI. The PCI range for hematocrit was: \>0.075 decrease from Baseline (low), \>1.02 x upper limit normal (ULN) (high-male), \>1.17 x ULN (high-female). The PCI range for hemoglobin was: \>25 decrease from Baseline (low), \>1.03 x ULN (high-male), \>1.13 x ULN (high-female). Data has been presented for the number of participants with hematology data values high from the PCI range in a consolidated format.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Hematology Values of PCI (Part B) Hematocrit, high	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Hematology Values of PCI (Part B) Hemoglobin, high	0 Participants	1 Participants	1 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population

Blood samples for chemistry assessments were collected at screening, fasting (Day -1), at 24hr post- dose (morning of Day 2), and at follow-up. Clinical chemistry parameter: Glucose (unit: millimoles per liter \[mmol/L\]) was assessed for abnormal high value of PCI. The normal range was 3.6 to 5.5 mmol/L

Outcome measures

Outcome measures
Measure	Part A n=6 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part A)	1 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

Population: Safety Population

Blood samples for chemistry assessments were collected at screening, on Day -2 (non-fasting), and prior to breakfast (early in the morning, fasting) on Days 1, 7, and on Day 15 prior to checkout, (=24hrs post-dose), and at follow-up. Clinical chemistry parameters: Aspartate amino transferase (unit: international unit per liter \[IU/L\]) and Total bilirubin (unit: micromoles per liter (µmol/L) were assessed for abnormal values of PCI. For aspartate aminotransferase the PCI range was \>=2 x ULN (high). For total bilirubin the PCI range was \>=1.5 x ULN (high).

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) Aspartate aminotransferase, high	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Chemistry Values of PCI (Part B) Total bilirubin, high	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population

Urinalysis parameters: Urine occult blood, Urine Glucose, Urine ketones and Urine protein were assessed for abnormal findings by dipstick analysis. The abnormalities were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome.

Outcome measures

Outcome measures
Measure	Part A n=6 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) Urine occult blood, Day 1, 24 hours, trace	1 Participants	—	—	—	—
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) Urine occult blood, follow up, trace	1 Participants	—	—	—	—
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) Urine glucose, Day 1, 24 hours, 3+	1 Participants	—	—	—	—
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) Urine glucose, follow up, 3+	1 Participants	—	—	—	—
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) Urine glucose, follow up, trace	2 Participants	—	—	—	—
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) Urine ketones, follow up, trace	2 Participants	—	—	—	—
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) Urine protein, Day 1, 24 hours, trace	1 Participants	—	—	—	—
Number of Participants With Abnormal Urinalysis Data Values by Dipstick Method (Part A) Urine protein, follow up, trace	2 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

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

Urinalysis parameters: Urine occult blood, Urine glucose, Urine ketones, Urine protein, White blood cells were assessed for abnormal findings by dipstick analysis. The abnormal findings were presented as trace, 1+, 2+ and 3+. Trace indicates lowest concentration of the mentioned parameters in urine and 3+ indicates highest concentration. Concentration of 3+ indicates worse outcome.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine ketones, follow up, trace	0 Participants	0 Participants	1 Participants	4 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, Day 7, pre-breakfast, 1+	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, Day 7, pre-breakfast, trace	1 Participants	1 Participants	2 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, Day 14, 24 hours, 1+	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, Day 14, 24 hours, trace	5 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, follow up, 1+	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, follow up, 2+	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, follow up, trace	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine occult blood, Day 1, pre-breakfast, 3+	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine occult blood, Day 1, pre-breakfast, trace	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine occult blood, Day 7, pre-breakfast, trace	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine occult blood, Day 14, 24 hours, trace	2 Participants	2 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine occult blood, follow up, trace	0 Participants	2 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 1, pre-breakfast, 1+	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 1, pre-breakfast, 2+	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 1, pre-breakfast, 3+	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 1, pre-breakfast, trace	0 Participants	2 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 7, pre-breakfast, 1+	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 7, pre-breakfast, 2+	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 7, pre-breakfast, trace	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 14, 24 hours, 3+	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, Day 14, 24 hours, trace	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, follow up, 1+	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, follow up, 2+	1 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, follow up, 3+	1 Participants	0 Participants	4 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine glucose, follow up, trace	2 Participants	2 Participants	1 Participants	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine ketones, Day 1, pre-breakfast, trace	0 Participants	1 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine ketones, Day 7, pre-breakfast, trace	0 Participants	0 Participants	1 Participants	2 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine ketones, Day 14, 24 hours, trace	0 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine ketones, follow up, 1+	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine protein, Day 1, pre-breakfast, trace	0 Participants	2 Participants	0 Participants	2 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine protein, Day 7, pre-breakfast, 1+	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine protein, Day 7, pre-breakfast, trace	1 Participants	2 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine protein, Day 14, 24 hours, trace	0 Participants	2 Participants	3 Participants	1 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine protein, follow up, 1+	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine protein, follow up, 2+	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) Urine protein, follow up, trace	3 Participants	3 Participants	4 Participants	4 Participants	1 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, Day 1, pre-breakfast, 1+	2 Participants	1 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Urinalysis Data Values (Part B) White blood cells, Day 1, pre-breakfast, trace	2 Participants	1 Participants	1 Participants	1 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.

Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urine albumin was assessed using quantitative analysis.

Outcome measures

Outcome measures
Measure	Part A n=1 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Value of Urine Albumin at Follow up (Part A)	6.0 milligrams per liter (mg/L) Standard Deviation NA Not available as only 1 participant was analyzed	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

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

Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urine albumin was assessed using quantitative analysis.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Value of Urine Albumin (Part B) Day 1, pre-breakfast	15.3 mg/L Standard Deviation 11.30	17.7 mg/L Standard Deviation 11.50	8.7 mg/L Standard Deviation 5.51	15.7 mg/L Standard Deviation 8.33	6.6 mg/L Standard Deviation 0.89
Mean Value of Urine Albumin (Part B) Day 7, pre-breakfast	8.0 mg/L Standard Deviation 1.73	19.5 mg/L Standard Deviation 27.67	24.5 mg/L Standard Deviation 20.51	24.0 mg/L Standard Deviation 22.60	7.3 mg/L Standard Deviation 1.53
Mean Value of Urine Albumin (Part B) Day 14, 24 hours	7.8 mg/L Standard Deviation 2.50	28.3 mg/L Standard Deviation 34.53	11.4 mg/L Standard Deviation 6.31	11.0 mg/L Standard Deviation 3.56	10.4 mg/L Standard Deviation 8.88
Mean Value of Urine Albumin (Part B) Follow up	54.0 mg/L Standard Deviation 78.01	26.1 mg/L Standard Deviation 35.34	17.6 mg/L Standard Deviation 13.87	29.5 mg/L Standard Deviation 34.65	11.2 mg/L Standard Deviation 5.17

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population

Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral.

Outcome measures

Outcome measures
Measure	Part A n=6 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Value of Urine pH (Part A) Day 1, 24 hours	6.17 pH Standard Deviation 0.258	—	—	—	—
Mean Value of Urine pH (Part A) Follow up	5.92 pH Standard Deviation 0.376	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

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

Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameters included urine pH assessed using dipstick analysis. pH is calculated on a scale of 0 to 14, such that, the lower the number, more acidic the urine and higher the number, more alkaline the urine with 7 being neutral.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Value of Urine pH (Part B) Day 1, pre-breakfast	6.04 pH Standard Deviation 0.499	6.04 pH Standard Deviation 0.431	6.04 pH Standard Deviation 0.257	6.03 pH Standard Deviation 0.399	5.92 pH Standard Deviation 0.344
Mean Value of Urine pH (Part B) Day 7, pre-breakfast	6.11 pH Standard Deviation 0.446	5.85 pH Standard Deviation 0.240	6.00 pH Standard Deviation 0.369	6.07 pH Standard Deviation 0.458	6.04 pH Standard Deviation 0.380
Mean Value of Urine pH (Part B) Day 14, 24 hours	5.96 pH Standard Deviation 0.414	6.04 pH Standard Deviation 0.247	6.17 pH Standard Deviation 0.326	6.07 pH Standard Deviation 0.267	6.08 pH Standard Deviation 0.277
Mean Value of Urine pH (Part B) Follow up	6.15 pH Standard Deviation 0.747	5.88 pH Standard Deviation 0.483	5.96 pH Standard Deviation 0.396	6.08 pH Standard Deviation 0.572	5.88 pH Standard Deviation 0.311

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population. Only those participants with data available at the indicated time points were analyzed.

Urine samples were collected at screening, Day -1, at 24hr post- dose (Day 2), and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine .

Outcome measures

Outcome measures
Measure	Part A n=5 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Value of Urine Specific Gravity (Part A) Day 1, 24 hours	1.0150 Ratio Standard Deviation 0.00500	—	—	—	—
Mean Value of Urine Specific Gravity (Part A) Follow up	1.0210 Ratio Standard Deviation 0.00224	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

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

Urine samples were collected at screening, on Day -2, and on Days 1, 7, 15 and at follow-up. Urinalysis parameter include urine specific gravity. Urinary specific gravity is a measure of the concentration of solutes in the urine . It measures the ratio of urine density compared with water density and provides information on the kidney's ability to concentrate urine .

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Value of Urine Specific Gravity (Part B) Day 1, pre-breakfast	1.0127 Ratio Standard Deviation 0.00518	1.0144 Ratio Standard Deviation 0.00417	1.0125 Ratio Standard Deviation 0.00418	1.0132 Ratio Standard Deviation 0.00513	1.0135 Ratio Standard Deviation 0.00580
Mean Value of Urine Specific Gravity (Part B) Day 7, pre-breakfast	1.0144 Ratio Standard Deviation 0.00464	1.0177 Ratio Standard Deviation 0.00564	1.0150 Ratio Standard Deviation 0.00447	1.0125 Ratio Standard Deviation 0.00380	1.0141 Ratio Standard Deviation 0.00539
Mean Value of Urine Specific Gravity (Part B) Day 14, 24 hours	1.0170 Ratio Standard Deviation 0.00587	1.0161 Ratio Standard Deviation 0.00651	1.0143 Ratio Standard Deviation 0.00607	1.0127 Ratio Standard Deviation 0.00410	1.0138 Ratio Standard Deviation 0.00433
Mean Value of Urine Specific Gravity (Part B) Follow up	1.0200 Ratio Standard Deviation 0.00661	1.0163 Ratio Standard Deviation 0.00443	1.0185 Ratio Standard Deviation 0.00669	1.0172 Ratio Standard Deviation 0.00618	1.0165 Ratio Standard Deviation 0.00669

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population

Assessment of vital signs (including systolic, diastolic blood pressure and heart rate) was performed at one time point at Screening, at follow-up and pre-breakfast on Day -1. On Day 1, they were taken at pre-breakfast, 1 hour, 3, 4, 6, 10, 16 and 24 hours post-dose. Assessments were made in triplicate at the pre-breakfast time point, and single assessments were made at all other times. Assessments were performed after resting in a supine or semi-supine position for at least 10 minutes. PCI value of systolic blood pressure: \<85 and \>160 millimeter of mercury (mmHg). PCI value of diastolic blood pressure: \<45 and \>100 mmHg. PCI value of heart rate: \<40 and \>110 beats per minute.

Outcome measures

Outcome measures
Measure	Part A n=6 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Vital Signs of PCI (Part A) Blood pressure (systolic and diastolic)	0 Participants	—	—	—	—
Number of Participants With Abnormal Vital Signs of PCI (Part A) Heart rate, high	1 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

Population: Safety Population.

Assessment of vital signs (including systolic and diastolic blood pressure and heart rate) was performed at Screening, pre-breakfast on Days -1 to 14 in a fasting state early in the morning (prior to morning dosing on Days 1-14), and at Follow-up. On Days 1, 7 and 14, they were taken at 1, 3, 6, 9, 12 and 24 hours after the morning dose. At each time point, assessment was performed after resting in a supine or semi-supine position for at least 10 minutes.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Vital Signs of PCI (Part B) Systolic blood pressure, high	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Vital Signs of PCI (Part B) Heart rate	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 2) in Part A

Population: Safety Population.

ECGs were taken at Screening, pre-breakfast on Day -1, on Day 1 (pre-breakfast, 1 hour, 2, 3, 4, 6, 8, 13, 24hours post-dose), and at follow-up. Assessments were made in triplicate on Day 1 at the pre-breakfast time point, and single assessments were made at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS).

Outcome measures

Outcome measures
Measure	Part A n=6 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, pre-breakfast 1, abnormal-NCS	3 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, pre-breakfast 2, abnormal-NCS	2 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, pre-breakfast 3, abnormal-NCS	2 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, 1 hour, abnormal-NCS	1 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, 2 hour, abnormal-NCS	3 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, 13 hour, abnormal-NCS	1 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, 24 hour, abnormal-NCS	2 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, 3 hour, abnormal-NCS	3 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, 4 hour, abnormal-NCS	2 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, 6 hour, abnormal-NCS	1 Participants	—	—	—	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part A) Day 1, 8 hour, abnormal-NCS	3 Participants	—	—	—	—

PRIMARY outcome

Timeframe: Up to 10 days after discharge (Day 15) in Part B

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

ECGs were taken at Screening, pre-breakfast on Day -1 and at Follow-up. On Days 1, 7 and 14 ECGs were taken pre-breakfast (fasting) and at 1, 2, 4, 6, 8, 12 and 24hours post-dose. Triplicate ECGs were taken at the pre-breakfast time point, and single assessments were taken at all other times. ECGs were taken in supine position. The data has been presented as abnormal- not clinically significant (NCS) and abnormal-clinically significant (CS).

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=15 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, pre-breakfast 1, abnormal-NCS	2 Participants	2 Participants	4 Participants	3 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, pre-breakfast 2, abnormal-NCS	1 Participants	2 Participants	5 Participants	2 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, pre-breakfast 3, abnormal-NCS	1 Participants	2 Participants	5 Participants	2 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, 1 hour, abnormal-NCS	1 Participants	1 Participants	4 Participants	6 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, 1 hour, abnormal-CS	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, 2 hour, abnormal-NCS	1 Participants	1 Participants	3 Participants	4 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, 8 hour, abnormal-NCS	1 Participants	4 Participants	4 Participants	4 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, 12 hour, abnormal-NCS	1 Participants	3 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, 24 hour, abnormal-NCS	3 Participants	2 Participants	3 Participants	3 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, pre-breakfast 1, abnormal-NCS	1 Participants	2 Participants	4 Participants	3 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, pre-breakfast 2, abnormal-NCS	2 Participants	3 Participants	4 Participants	3 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, 4 hour, abnormal-NCS	1 Participants	2 Participants	4 Participants	4 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 1, 6 hour, abnormal-NCS	2 Participants	2 Participants	4 Participants	4 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Follow up-NCS	1 Participants	2 Participants	2 Participants	3 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, pre-breakfast 3, abnormal-NCS	1 Participants	3 Participants	3 Participants	2 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, 1 hour, abnormal-NCS	0 Participants	1 Participants	5 Participants	2 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, 2 hour, abnormal-NCS	0 Participants	3 Participants	5 Participants	3 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, 4 hour, abnormal-NCS	0 Participants	2 Participants	4 Participants	3 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, 6 hour, abnormal-NCS	0 Participants	3 Participants	3 Participants	2 Participants	5 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, 8 hour, abnormal-NCS	1 Participants	4 Participants	4 Participants	2 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, 12 hour, abnormal-NCS	2 Participants	2 Participants	3 Participants	2 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 7, 24 hour, abnormal-NCS	1 Participants	3 Participants	4 Participants	3 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, pre-breakfast 1, abnormal-NCS	1 Participants	1 Participants	4 Participants	3 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, pre-breakfast 2, abnormal-NCS	1 Participants	2 Participants	5 Participants	3 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, pre-breakfast 3, abnormal-NCS	1 Participants	1 Participants	4 Participants	3 Participants	4 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, 1 hour, abnormal-NCS	1 Participants	3 Participants	5 Participants	2 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, 2 hour, abnormal-NCS	1 Participants	2 Participants	4 Participants	3 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, 4 hour, abnormal-NCS	0 Participants	2 Participants	3 Participants	3 Participants	3 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, 6 hour, abnormal-NCS	0 Participants	2 Participants	4 Participants	2 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, 8 hour, abnormal-NCS	1 Participants	1 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, 12 hour, abnormal-NCS	1 Participants	2 Participants	5 Participants	3 Participants	2 Participants
Number of Participants With Abnormal Electrocardiogram (ECG) Findings (Part B) Day 14, 24 hour, abnormal-NCS	1 Participants	1 Participants	5 Participants	3 Participants	3 Participants

PRIMARY outcome

Timeframe: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.

Population: The PK Population included participants from the Safety Population who had any PK parameter estimated. Only those participants with data available at the indicated time points were analyzed.

Blood samples for the determination of pharmacokinetics (PK) were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-last) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

Outcome measures

Outcome measures
Measure	Part A n=4 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours [AUC (0-24)] and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-last)] Following a Single Dose of GSK1292263 (Part A) AUC (0-24)	7046.25 nanograms hour per milliliter (ng*hr/mL) Geometric Coefficient of Variation 11.090	—	—	—	—
Area Under the Concentration-time Curve From Zero (Pre-dose) to 24 Hours [AUC (0-24)] and AUC From Time Zero (Pre-dose) to Last Time of Quantifiable Concentration (AUC [0-last)] Following a Single Dose of GSK1292263 (Part A) AUC (0-last)	10099.35 nanograms hour per milliliter (ng*hr/mL) Geometric Coefficient of Variation 14.332	—	—	—	—

PRIMARY outcome

Timeframe: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.

Population: PK Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data.

Outcome measures

Outcome measures
Measure	Part A n=4 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Maximum Observed Concentration (Cmax) Following a Single Dose of GSK1292263 (Part A)	582.619 nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 28.0710	—	—	—	—

PRIMARY outcome

Timeframe: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.

Population: PK Population. Only those participants with data available at the indicated time points were analyzed.

Blood samples for the determination of PK were collected on Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose. PK samples for 2 participants were not analyzed. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only.

Outcome measures

Outcome measures
Measure	Part A n=4 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) and Time of Occurrence of Cmax (Tmax) Following a Single Dose of GSK1292263 (Part A) Tlag	0.000 hour Interval 0.0 to 0.5	—	—	—	—
Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) and Time of Occurrence of Cmax (Tmax) Following a Single Dose of GSK1292263 (Part A) Tmax	5.00 hour Interval 4.0 to 13.0	—	—	—	—

PRIMARY outcome

Timeframe: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.

Outcome measure was added with caveat "as data permits". The data for CL/F was not collected.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.

Population: PK Population

Outcome measure was added with caveat "as data permits". The data for V/F was not collected.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.

Population: PK Population

Outcome measure was added with caveat "as data permits". The data for AUC (0-inf) was not collected.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: On Day 1 Immediately pre-dose (time 0) and at 0.5, 1, 2, 3, 4, 6, 8, 13, 24 and 48 hours post-dose.

Population: PK Population

Outcome measure was added with caveat "as data permits". The data for t1/2 was not collected.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).

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

Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Cmax was determined directly from the raw concentration-time data.

Outcome measures

Outcome measures
Measure	Part A n=13 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=12 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=15 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Cmax Following Repeat Dose of GSK1292263 (Part B) Day 1	278.451 ng/mL Geometric Coefficient of Variation 36.5951	686.845 ng/mL Geometric Coefficient of Variation 33.1747	610.586 ng/mL Geometric Coefficient of Variation 29.2427	—	—
Cmax Following Repeat Dose of GSK1292263 (Part B) Day 7	416.441 ng/mL Geometric Coefficient of Variation 30.0099	872.843 ng/mL Geometric Coefficient of Variation 22.2509	738.918 ng/mL Geometric Coefficient of Variation 39.1209	—	—
Cmax Following Repeat Dose of GSK1292263 (Part B) Day 14	457.716 ng/mL Geometric Coefficient of Variation 20.4386	902.325 ng/mL Geometric Coefficient of Variation 30.0011	664.505 ng/mL Geometric Coefficient of Variation 37.8497	—	—

PRIMARY outcome

Timeframe: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).

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

Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. Tmax was determined directly from the raw concentration-time data. Tlag was determined as the time of the sample preceding the first quantifiable concentration, on Day 1 only.

Outcome measures

Outcome measures
Measure	Part A n=13 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=12 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=15 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) Tlag, Day1	0.000 hour Interval 0.0 to 1.0	0.000 hour Interval 0.0 to 0.0	0.000 hour Interval 0.0 to 1.0	—	—
Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) Tmax, Day 1	14.00 hour Interval 6.0 to 18.0	14.00 hour Interval 4.0 to 18.0	4.0 hour Interval 4.0 to 12.0	—	—
Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) Tmax, Day 7	4.00 hour Interval 4.0 to 6.0	4.00 hour Interval 0.0 to 4.0	4.00 hour Interval 2.0 to 10.1	—	—
Tmax and Tlag Following Repeat Dose of GSK1292263 (Part B) Tmax, Day 14	4.00 hour Interval 4.0 to 24.0	13.00 hour Interval 1.0 to 24.0	4.0 hour Interval 1.0 to 10.2	—	—

PRIMARY outcome

Timeframe: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).

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

Serial blood samples for the determination of the PK of GSK1292263 were collected on Days 1, 7 and 14. Blood samples for PK were collected on Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, blood samples for PK were collected at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen). When planned PK sampling resulted in multiple samples at the same time point, only one sample was collected. The PK parameters were calculated by standard non-compartmental analysis. AUC (0-10) and AUC (0-24) were determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

Outcome measures

Outcome measures
Measure	Part A n=13 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=12 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=15 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) AUC (0-10), Day 1	1143.35 ng*hr/mL Geometric Coefficient of Variation 36.439	3149.94 ng*hr/mL Geometric Coefficient of Variation 38.937	NA ng*hr/mL Geometric Coefficient of Variation NA Data was not analyzed at this time point	—	—
AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) AUC (0-10), Day 7	2930.47 ng*hr/mL Geometric Coefficient of Variation 21.366	6472.68 ng*hr/mL Geometric Coefficient of Variation 29.790	5205.86 ng*hr/mL Geometric Coefficient of Variation 31.529	—	—
AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) AUC (0-10), Day 14	3130.50 ng*hr/mL Geometric Coefficient of Variation 22.430	6057.41 ng*hr/mL Geometric Coefficient of Variation 32.784	NA ng*hr/mL Geometric Coefficient of Variation NA Data was not analyzed at this time point	—	—
AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) AUC (0-24), Day 1	3775.76 ng*hr/mL Geometric Coefficient of Variation 30.915	9968.88 ng*hr/mL Geometric Coefficient of Variation 39.959	6791.90 ng*hr/mL Geometric Coefficient of Variation 24.550	—	—
AUC From Time Zero (Pre-dose) to 10 Hours [AUC (0-10)] and AUC (0-24) Following Repeat Dose of GSK1292263 (Part B) AUC (0-24), Day 14	7785.24 ng*hr/mL Geometric Coefficient of Variation 19.152	15479.48 ng*hr/mL Geometric Coefficient of Variation 33.009	9391.30 ng*hr/mL Geometric Coefficient of Variation 32.948	—	—

PRIMARY outcome

Timeframe: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose. On Day 7, at pre-dose (post-breakfast), 1, 2, 4 (pre-lunch), 6 and 10 (immediately post-dinner, pre-dose for BID regimen).

Population: PK population

Outcome measure was added with caveat "as data permits". The data for T1/2 was not collected.

Outcome measures

Outcome data not reported

PRIMARY outcome

Timeframe: On Days 1 and 14, at immediately pre-morning dose, 1, 2, 4, 6, 8, 10, 11, 12, 14, 16, 18, 24 and 48 hours post-morning dose.

Population: PK Population. Only those participants with data available at the indicated time points were analyzed.

Accumulation ratio (Ro) was derived as: Ro = Day 14 morning AUC(0-10)/Day 1 morning AUC(0-10) (for BID regimens only). Ro = Day 14 AUC(0-24)/Day 1 AUC(0-24) (for both BID and once daily regimens). Accumulation ratio (RCmax)= Day 14 Cmax/Day 1 Cmax. RCmax was not computed for each dosing period (morning and evening).

Outcome measures

Outcome measures
Measure	Part A n=13 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=12 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=14 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) AUC (0-10)	2.7380 Ratio Interval 2.4706 to 3.0344	1.9230 Ratio Interval 1.6883 to 2.1903	NA Ratio Data was not analyzed at this time point	—	—
Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) AUC (0-24)	2.0619 Ratio Interval 1.8432 to 2.3065	1.5528 Ratio Interval 1.3748 to 1.7538	1.3730 Ratio Interval 1.2219 to 1.5429	—	—
Mean Accumulation Ratio by AUC (0-10), AUC (0-24) and Cmax for GSK1292263 (Part B) Cmax	1.6438 Ratio Interval 1.4256 to 1.8954	1.3137 Ratio Interval 1.2009 to 1.4372	1.1077 Ratio Interval 0.9659 to 1.2704	—	—

PRIMARY outcome

Timeframe: Baseline and at pre-breakfast on Day 1 and 24 h post-dose.

Population: The Pharmacodynamic (PD) Population included participants from the Safety Population who had any PD parameter estimated. Only those participants with data available at the indicated time points were analyzed.

Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.

Outcome measures

Outcome measures
Measure	Part A n=4 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Change From Baseline in Mean Fasted Glucose Value (Part A)	0.17 millimoles per liter (mmol/L) Geometric Coefficient of Variation -199.736	—	—	—	—

PRIMARY outcome

Timeframe: Baseline and at pre-breakfast on Day 1 and 24 hours post-dose.

Population: PD Population. Only those participants with data available at the indicated time points were analyzed.

Baseline was considered to be Day 1 pre-breakfast. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.

Outcome measures

Outcome measures
Measure	Part A n=4 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Change From Baseline in Mean Fasted Insulin Value (Part A)	3.45 picomoles per liter (pmol/L) Geometric Coefficient of Variation -187.128	—	—	—	—

PRIMARY outcome

Timeframe: Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.

Population: PD Population.

Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=14 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=12 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Change From Baseline in Mean Fasted Glucose Value (Part B) Day 7, pre-breakfast	-0.53 mmol/L Interval -0.92 to -0.14	-0.74 mmol/L Interval -1.22 to -0.27	-0.28 mmol/L Interval -1.15 to 0.58	0.21 mmol/L Interval -0.53 to 0.95	-1.75 mmol/L Interval -2.2 to -1.29
Change From Baseline in Mean Fasted Glucose Value (Part B) Day 14, pre-breakfast	-0.74 mmol/L Interval -1.3 to -0.18	-1.57 mmol/L Interval -2.39 to -0.75	-0.81 mmol/L Interval -1.77 to 0.16	-0.11 mmol/L Interval -0.96 to 0.75	-1.83 mmol/L Interval -2.65 to -1.02
Change From Baseline in Mean Fasted Glucose Value (Part B) Day 14, 24 hours	-0.01 mmol/L Interval -0.94 to 0.92	-0.57 mmol/L Interval -1.49 to 0.36	0.66 mmol/L Interval -0.31 to 1.64	0.68 mmol/L Interval 0.09 to 1.27	-1.06 mmol/L Interval -1.87 to -0.26

PRIMARY outcome

Timeframe: Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.

Population: PD Population.

Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=14 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=12 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Change From Baseline in Mean Fasted Insulin Value (Part B) Day 7, pre-breakfast	-2.74 pmol/L Interval -15.26 to 9.77	-1.84 pmol/L Interval -9.22 to 5.53	-26.34 pmol/L Interval -57.25 to 4.57	-22.99 pmol/L Interval -39.68 to -6.31	2.07 pmol/L Interval -15.96 to 20.11
Change From Baseline in Mean Fasted Insulin Value (Part B) Day 14, pre-breakfast	4.84 pmol/L Interval -8.97 to 18.65	6.22 pmol/L Interval -5.01 to 17.46	-13.48 pmol/L Interval -36.79 to 9.82	-33.26 pmol/L Interval -53.15 to -13.37	4.43 pmol/L Interval -5.65 to 14.5
Change From Baseline in Mean Fasted Insulin Value (Part B) Day 14, 24 hours	23.25 pmol/L Interval 5.53 to 40.96	4.97 pmol/L Interval -19.94 to 29.87	-12.54 pmol/L Interval -40.87 to 15.8	-17.52 pmol/L Interval -41.26 to 6.23	27.47 pmol/L Interval 2.5 to 52.43

PRIMARY outcome

Timeframe: At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.

Population: PD Population.

Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=14 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=12 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Post Meal Glucose Value (Part B) Day 14, post-dinner, 0.5 hour	8.17 mmol/L Interval 6.86 to 9.47	7.99 mmol/L Interval 6.95 to 9.03	9.37 mmol/L Interval 8.09 to 10.65	10.41 mmol/L Interval 8.96 to 11.86	7.29 mmol/L Interval 6.4 to 8.19
Mean Post Meal Glucose Value (Part B) Day 14, post-dinner, 1 hour	11.07 mmol/L Interval 9.53 to 12.61	11.20 mmol/L Interval 10.03 to 12.36	12.21 mmol/L Interval 10.72 to 13.7	12.56 mmol/L Interval 10.99 to 14.12	9.43 mmol/L Interval 8.0 to 10.86
Mean Post Meal Glucose Value (Part B) Day 14, post-dinner, 1.5 hour	11.65 mmol/L Interval 9.89 to 13.41	11.81 mmol/L Interval 10.43 to 13.19	13.01 mmol/L Interval 11.38 to 14.64	13.03 mmol/L Interval 11.57 to 14.49	10.41 mmol/L Interval 8.48 to 12.33
Mean Post Meal Glucose Value (Part B) Day 14, post-dinner, 2 hour	11.42 mmol/L Interval 9.64 to 13.21	11.27 mmol/L Interval 9.62 to 12.93	12.07 mmol/L Interval 10.76 to 13.38	12.60 mmol/L Interval 11.11 to 14.09	10.07 mmol/L Interval 8.11 to 12.03
Mean Post Meal Glucose Value (Part B) Day -1, post-breakfast, 0.5 hour	13.75 mmol/L Interval 12.8 to 14.7	13.51 mmol/L Interval 12.35 to 14.67	14.68 mmol/L Interval 13.74 to 15.62	13.04 mmol/L Interval 11.67 to 14.42	13.60 mmol/L Interval 12.63 to 14.56
Mean Post Meal Glucose Value (Part B) Day -1, post-breakfast, 1 hour	13.62 mmol/L Interval 12.58 to 14.66	13.42 mmol/L Interval 12.39 to 14.45	14.48 mmol/L Interval 13.49 to 15.48	13.43 mmol/L Interval 12.06 to 14.8	13.12 mmol/L Interval 11.88 to 14.37
Mean Post Meal Glucose Value (Part B) Day -1, post-breakfast, 1.5 hour	12.56 mmol/L Interval 11.41 to 13.71	12.12 mmol/L Interval 10.9 to 13.34	12.94 mmol/L Interval 11.62 to 14.26	12.02 mmol/L Interval 10.24 to 13.8	11.39 mmol/L Interval 10.17 to 12.6
Mean Post Meal Glucose Value (Part B) Day -1, post-breakfast, 2 hour	10.71 mmol/L Interval 9.73 to 11.69	10.55 mmol/L Interval 9.03 to 12.06	11.50 mmol/L Interval 9.99 to 13.01	10.67 mmol/L Interval 9.04 to 12.29	9.75 mmol/L Interval 8.46 to 11.03
Mean Post Meal Glucose Value (Part B) Day -1, post-breakfast, 3 hour	7.78 mmol/L Interval 7.02 to 8.53	8.48 mmol/L Interval 6.68 to 10.28	8.68 mmol/L Interval 7.02 to 10.33	8.46 mmol/L Interval 6.99 to 9.93	7.73 mmol/L Interval 6.91 to 8.55
Mean Post Meal Glucose Value (Part B) Day -1, post-lunch, 0.5 hour	7.46 mmol/L Interval 6.48 to 8.45	8.90 mmol/L Interval 7.35 to 10.45	8.56 mmol/L Interval 7.54 to 9.58	8.58 mmol/L Interval 7.61 to 9.56	7.93 mmol/L Interval 7.04 to 8.83
Mean Post Meal Glucose Value (Part B) Day -1, post-lunch, 1 hour	10.31 mmol/L Interval 9.47 to 11.15	11.19 mmol/L Interval 10.09 to 12.29	10.71 mmol/L Interval 9.85 to 11.57	10.12 mmol/L Interval 8.76 to 11.48	10.36 mmol/L Interval 9.34 to 11.39
Mean Post Meal Glucose Value (Part B) Day -1, post-lunch, 1.5 hour	11.07 mmol/L Interval 9.99 to 12.14	11.17 mmol/L Interval 9.75 to 12.58	11.64 mmol/L Interval 10.54 to 12.74	10.45 mmol/L Interval 9.02 to 11.89	10.69 mmol/L Interval 9.51 to 11.87
Mean Post Meal Glucose Value (Part B) Day -1, post-lunch, 2 hour	11.31 mmol/L Interval 10.11 to 12.51	10.82 mmol/L Interval 9.42 to 12.21	11.75 mmol/L Interval 10.72 to 12.78	10.11 mmol/L Interval 8.82 to 11.39	10.72 mmol/L Interval 9.56 to 11.88
Mean Post Meal Glucose Value (Part B) Day -1, post-lunch, 3 hour	11.05 mmol/L Interval 9.95 to 12.16	10.05 mmol/L Interval 8.5 to 11.6	11.25 mmol/L Interval 10.08 to 12.43	10.37 mmol/L Interval 9.03 to 11.71	9.92 mmol/L Interval 8.8 to 11.03
Mean Post Meal Glucose Value (Part B) Day -1, post-dinner, 0.5 hour	9.28 mmol/L Interval 7.95 to 10.6	9.19 mmol/L Interval 8.14 to 10.25	8.78 mmol/L Interval 7.85 to 9.71	8.92 mmol/L Interval 7.86 to 9.98	8.39 mmol/L Interval 7.56 to 9.22
Mean Post Meal Glucose Value (Part B) Day -1, post-dinner, 1 hour	11.15 mmol/L Interval 9.83 to 12.47	11.27 mmol/L Interval 9.88 to 12.67	11.00 mmol/L Interval 9.75 to 12.25	10.77 mmol/L Interval 9.64 to 11.9	10.27 mmol/L Interval 9.33 to 11.22
Mean Post Meal Glucose Value (Part B) Day -1, post-dinner, 1.5 hour	11.45 mmol/L Interval 10.13 to 12.77	10.97 mmol/L Interval 9.46 to 12.49	10.99 mmol/L Interval 9.97 to 12.01	10.94 mmol/L Interval 9.62 to 12.26	10.52 mmol/L Interval 9.47 to 11.58
Mean Post Meal Glucose Value (Part B) Day -1, post-dinner, 2 hour	11.67 mmol/L Interval 10.15 to 13.2	10.76 mmol/L Interval 9.18 to 12.35	10.81 mmol/L Interval 9.76 to 11.85	10.98 mmol/L Interval 9.57 to 12.39	10.18 mmol/L Interval 9.09 to 11.27
Mean Post Meal Glucose Value (Part B) Day -1, post-dinner, 3 hour	11.58 mmol/L Interval 9.76 to 13.39	10.41 mmol/L Interval 8.83 to 11.99	10.34 mmol/L Interval 9.45 to 11.23	10.48 mmol/L Interval 9.2 to 11.75	9.66 mmol/L Interval 8.49 to 10.84
Mean Post Meal Glucose Value (Part B) Day 14, post-breakfast, 0.5 hour	14.16 mmol/L Interval 12.45 to 15.86	13.13 mmol/L Interval 11.86 to 14.41	14.96 mmol/L Interval 13.89 to 16.03	13.83 mmol/L Interval 12.6 to 15.05	12.26 mmol/L Interval 10.53 to 13.98
Mean Post Meal Glucose Value (Part B) Day 14, post-breakfast, 1 hour	14.02 mmol/L Interval 11.79 to 16.24	13.32 mmol/L Interval 11.47 to 15.17	14.23 mmol/L Interval 12.91 to 15.55	14.32 mmol/L Interval 12.95 to 15.7	12.03 mmol/L Interval 10.17 to 13.89
Mean Post Meal Glucose Value (Part B) Day 14, post-breakfast, 1.5 hour	12.69 mmol/L Interval 11.25 to 14.13	11.58 mmol/L Interval 9.63 to 13.52	12.96 mmol/L Interval 11.14 to 14.78	13.07 mmol/L Interval 11.37 to 14.76	10.55 mmol/L Interval 8.66 to 12.43
Mean Post Meal Glucose Value (Part B) Day 14, post-breakfast, 2 hour	11.15 mmol/L Interval 9.83 to 12.46	9.98 mmol/L Interval 8.03 to 11.93	10.93 mmol/L Interval 9.1 to 12.76	11.11 mmol/L Interval 9.2 to 13.02	9.10 mmol/L Interval 7.21 to 11.0
Mean Post Meal Glucose Value (Part B) Day 14, post-breakfast, 3 hour	7.56 mmol/L Interval 6.14 to 8.98	6.96 mmol/L Interval 5.32 to 8.61	8.20 mmol/L Interval 6.58 to 9.82	8.73 mmol/L Interval 7.04 to 10.43	6.69 mmol/L Interval 5.06 to 8.32
Mean Post Meal Glucose Value (Part B) Day 14, post-lunch, 0.5 hour	7.43 mmol/L Interval 6.43 to 8.44	8.73 mmol/L Interval 7.66 to 9.8	10.07 mmol/L Interval 8.84 to 11.31	8.70 mmol/L Interval 7.76 to 9.63	7.77 mmol/L Interval 6.66 to 8.89
Mean Post Meal Glucose Value (Part B) Day 14, post-lunch, 1 hour	9.61 mmol/L Interval 8.42 to 10.8	10.59 mmol/L Interval 9.29 to 11.88	11.96 mmol/L Interval 10.62 to 13.29	10.42 mmol/L Interval 9.24 to 11.59	8.38 mmol/L Interval 7.47 to 9.28
Mean Post Meal Glucose Value (Part B) Day 14, post-lunch, 1.5 hour	10.38 mmol/L Interval 9.23 to 11.53	10.80 mmol/L Interval 9.43 to 12.17	12.33 mmol/L Interval 11.25 to 13.41	11.12 mmol/L Interval 9.69 to 12.55	8.83 mmol/L Interval 7.78 to 9.88
Mean Post Meal Glucose Value (Part B) Day 14, post-lunch, 2 hour	10.83 mmol/L Interval 9.25 to 12.4	10.51 mmol/L Interval 9.15 to 11.88	12.09 mmol/L Interval 10.85 to 13.33	10.87 mmol/L Interval 9.48 to 12.27	8.84 mmol/L Interval 7.78 to 9.91
Mean Post Meal Glucose Value (Part B) Day 14, post-lunch, 3 hour	10.51 mmol/L Interval 8.71 to 12.3	9.71 mmol/L Interval 8.03 to 11.4	10.57 mmol/L Interval 9.12 to 12.01	10.44 mmol/L Interval 8.91 to 11.96	8.90 mmol/L Interval 7.76 to 10.05
Mean Post Meal Glucose Value (Part B) Day 14, post-dinner, 3 hour	10.43 mmol/L Interval 8.77 to 12.1	9.78 mmol/L Interval 7.7 to 11.87	10.69 mmol/L Interval 9.24 to 12.13	11.75 mmol/L Interval 10.17 to 13.32	8.80 mmol/L Interval 7.41 to 10.2

PRIMARY outcome

Timeframe: At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.

Population: PD Population.

Blood samples were collected on Days -1 and 14, post-breakfast at 0.5, 1, 1.5, 2 and 3 hours post dose. For lunch (approximately 4 hours post morning dose) samples were collected at the following times after starting each meal: 0.5, 1, 1.5, 2 and 3 hours. For the evening meal (approximately 10 hours post morning dose), samples were taken at 0.5, 1, 1.5, 2 and 3 hours post dinner.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=14 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=12 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Mean Post Meal Insulin Value (Part B) Day -1, post-breakfast, 0.5 hour	201.81 pmol/L Interval 120.26 to 283.36	185.34 pmol/L Interval 136.03 to 234.64	270.35 pmol/L Interval 139.59 to 401.11	264.15 pmol/L Interval 183.44 to 344.87	219.24 pmol/L Interval 146.34 to 292.15
Mean Post Meal Insulin Value (Part B) Day -1, post-breakfast, 1 hour	222.44 pmol/L Interval 153.65 to 291.23	258.37 pmol/L Interval 176.77 to 339.98	296.05 pmol/L Interval 161.61 to 430.5	338.58 pmol/L Interval 218.57 to 458.59	251.79 pmol/L Interval 167.51 to 336.07
Mean Post Meal Insulin Value (Part B) Day -1, post-breakfast, 1.5 hour	251.01 pmol/L Interval 161.79 to 340.24	246.76 pmol/L Interval 177.95 to 315.57	318.38 pmol/L Interval 155.32 to 481.44	351.10 pmol/L Interval 239.19 to 463.01	237.46 pmol/L Interval 153.03 to 321.9
Mean Post Meal Insulin Value (Part B) Day -1, post-breakfast, 2 hour	233.85 pmol/L Interval 153.97 to 313.73	221.27 pmol/L Interval 147.26 to 295.28	258.69 pmol/L Interval 108.85 to 408.52	304.66 pmol/L Interval 205.71 to 403.6	196.53 pmol/L Interval 154.15 to 238.91
Mean Post Meal Insulin Value (Part B) Day -1, post-breakfast, 3 hour	131.95 pmol/L Interval 77.37 to 186.53	114.67 pmol/L Interval 85.59 to 143.75	162.58 pmol/L Interval 89.16 to 235.99	180.43 pmol/L Interval 130.54 to 230.32	106.98 pmol/L Interval 69.24 to 144.72
Mean Post Meal Insulin Value (Part B) Day -1, post-lunch, 0.5 hour	135.17 pmol/L Interval 88.11 to 182.22	115.21 pmol/L Interval 68.21 to 162.22	147.60 pmol/L Interval 80.48 to 214.71	187.22 pmol/L Interval 133.25 to 241.19	109.63 pmol/L Interval 85.23 to 134.03
Mean Post Meal Insulin Value (Part B) Day -1, post-lunch, 1 hour	193.80 pmol/L Interval 115.6 to 272.0	193.65 pmol/L Interval 127.73 to 259.57	186.02 pmol/L Interval 113.55 to 258.49	246.08 pmol/L Interval 180.25 to 311.9	180.49 pmol/L Interval 128.88 to 232.1
Mean Post Meal Insulin Value (Part B) Day -1, post-lunch, 1.5 hour	188.57 pmol/L Interval 123.3 to 253.85	208.37 pmol/L Interval 138.94 to 277.8	212.29 pmol/L Interval 135.68 to 288.9	289.19 pmol/L Interval 187.79 to 390.59	173.21 pmol/L Interval 124.34 to 222.08
Mean Post Meal Insulin Value (Part B) Day -1, post-lunch, 2 hour	235.41 pmol/L Interval 106.82 to 363.99	196.74 pmol/L Interval 156.56 to 236.93	218.67 pmol/L Interval 106.48 to 330.87	295.21 pmol/L Interval 185.14 to 405.29	202.47 pmol/L Interval 147.19 to 257.74
Mean Post Meal Insulin Value (Part B) Day -1, post-lunch, 3 hour	191.74 pmol/L Interval 120.96 to 262.51	171.15 pmol/L Interval 120.83 to 221.47	207.00 pmol/L Interval 98.15 to 315.86	270.43 pmol/L Interval 185.95 to 354.91	167.37 pmol/L Interval 125.31 to 209.42
Mean Post Meal Insulin Value (Part B) Day -1, post-dinner, 0.5 hour	132.04 pmol/L Interval 96.91 to 167.16	131.50 pmol/L Interval 81.6 to 181.39	150.10 pmol/L Interval 90.51 to 209.68	207.99 pmol/L Interval 152.25 to 263.72	104.16 pmol/L Interval 77.66 to 130.67
Mean Post Meal Insulin Value (Part B) Day -1, post-dinner, 1 hour	199.54 pmol/L Interval 142.13 to 256.94	205.59 pmol/L Interval 142.87 to 268.31	226.22 pmol/L Interval 127.02 to 325.41	274.72 pmol/L Interval 194.26 to 355.17	149.94 pmol/L Interval 122.06 to 177.81
Mean Post Meal Insulin Value (Part B) Day -1, post-dinner, 1.5 hour	195.55 pmol/L Interval 137.43 to 253.67	183.16 pmol/L Interval 135.87 to 230.46	206.80 pmol/L Interval 119.94 to 293.65	275.17 pmol/L Interval 200.75 to 349.59	171.08 pmol/L Interval 131.77 to 210.38
Mean Post Meal Insulin Value (Part B) Day -1, post-dinner, 2 hour	209.64 pmol/L Interval 130.71 to 288.56	205.06 pmol/L Interval 148.39 to 261.73	206.16 pmol/L Interval 122.43 to 289.88	266.34 pmol/L Interval 184.02 to 348.66	171.94 pmol/L Interval 126.51 to 217.36
Mean Post Meal Insulin Value (Part B) Day -1, post-dinner, 3 hour	176.48 pmol/L Interval 94.31 to 258.66	164.28 pmol/L Interval 110.19 to 218.37	172.36 pmol/L Interval 102.77 to 241.95	225.12 pmol/L Interval 156.84 to 293.39	155.62 pmol/L Interval 110.73 to 200.5
Mean Post Meal Insulin Value (Part B) Day 14, post-breakfast, 0.5 hour	258.61 pmol/L Interval 214.57 to 302.65	240.43 pmol/L Interval 163.71 to 317.15	241.13 pmol/L Interval 163.33 to 318.93	259.89 pmol/L Interval 166.35 to 353.44	268.74 pmol/L Interval 202.79 to 334.7
Mean Post Meal Insulin Value (Part B) Day 14, post-breakfast, 1 hour	304.23 pmol/L Interval 220.12 to 388.34	280.93 pmol/L Interval 201.95 to 359.91	297.58 pmol/L Interval 188.61 to 406.54	348.37 pmol/L Interval 199.81 to 496.92	354.57 pmol/L Interval 253.16 to 455.98
Mean Post Meal Insulin Value (Part B) Day 14, post-breakfast, 1.5 hour	297.57 pmol/L Interval 222.91 to 372.23	299.22 pmol/L Interval 183.56 to 414.89	272.63 pmol/L Interval 201.63 to 343.64	409.93 pmol/L Interval 231.64 to 588.22	300.33 pmol/L Interval 203.08 to 397.57
Mean Post Meal Insulin Value (Part B) Day 14, post-breakfast, 2 hour	283.85 pmol/L Interval 206.65 to 361.06	234.65 pmol/L Interval 167.0 to 302.29	229.72 pmol/L Interval 135.19 to 324.26	333.39 pmol/L Interval 175.19 to 491.6	246.53 pmol/L Interval 176.74 to 316.32
Mean Post Meal Insulin Value (Part B) Day 14, post-breakfast, 3 hour	161.67 pmol/L Interval 91.12 to 232.21	110.81 pmol/L Interval 79.94 to 141.68	122.31 pmol/L Interval 68.67 to 175.94	188.31 pmol/L Interval 120.35 to 256.27	117.21 pmol/L Interval 64.59 to 169.83
Mean Post Meal Insulin Value (Part B) Day 14, post-lunch, 0.5 hour	153.65 pmol/L Interval 104.68 to 202.62	129.25 pmol/L Interval 88.96 to 169.54	126.26 pmol/L Interval 92.54 to 159.98	169.17 pmol/L Interval 122.63 to 215.71	155.68 pmol/L Interval 126.09 to 185.26
Mean Post Meal Insulin Value (Part B) Day 14, post-lunch, 1 hour	201.54 pmol/L Interval 133.12 to 269.95	169.74 pmol/L Interval 130.07 to 209.41	172.43 pmol/L Interval 128.88 to 215.99	190.65 pmol/L Interval 136.34 to 244.96	164.53 pmol/L Interval 133.23 to 195.83
Mean Post Meal Insulin Value (Part B) Day 14, post-lunch, 1.5 hour	229.56 pmol/L Interval 143.82 to 315.3	194.93 pmol/L Interval 141.31 to 248.55	179.44 pmol/L Interval 128.44 to 230.43	223.72 pmol/L Interval 148.81 to 298.63	184.69 pmol/L Interval 145.83 to 223.54
Mean Post Meal Insulin Value (Part B) Day 14, post-lunch, 2 hour	237.34 pmol/L Interval 153.62 to 321.05	214.66 pmol/L Interval 152.23 to 277.09	177.88 pmol/L Interval 131.02 to 224.73	227.81 pmol/L Interval 142.85 to 312.77	188.61 pmol/L Interval 140.47 to 236.75
Mean Post Meal Insulin Value (Part B) Day 14, post-lunch, 3 hour	219.31 pmol/L Interval 111.12 to 327.5	181.43 pmol/L Interval 132.84 to 230.02	137.67 pmol/L Interval 89.1 to 186.24	195.64 pmol/L Interval 140.45 to 250.83	172.22 pmol/L Interval 134.89 to 209.55
Mean Post Meal Insulin Value (Part B) Day 14, post-dinner, 0.5 hour	99.41 pmol/L Interval 60.27 to 138.56	98.57 pmol/L Interval 57.19 to 139.96	75.85 pmol/L Interval 46.65 to 105.04	137.16 pmol/L Interval 100.98 to 173.34	92.78 pmol/L Interval 67.46 to 118.09
Mean Post Meal Insulin Value (Part B) Day 14, post-dinner, 1 hour	204.76 pmol/L Interval 140.32 to 269.19	178.38 pmol/L Interval 129.51 to 227.25	141.59 pmol/L Interval 96.79 to 186.38	191.90 pmol/L Interval 132.03 to 251.77	156.48 pmol/L Interval 119.25 to 193.7
Mean Post Meal Insulin Value (Part B) Day 14, post-dinner, 1.5 hour	204.67 pmol/L Interval 138.63 to 270.71	210.90 pmol/L Interval 150.5 to 271.3	163.94 pmol/L Interval 111.91 to 215.96	215.57 pmol/L Interval 137.16 to 293.98	179.94 pmol/L Interval 140.71 to 219.17
Mean Post Meal Insulin Value (Part B) Day 14, post-dinner, 2 hour	237.14 pmol/L Interval 128.24 to 346.03	220.97 pmol/L Interval 159.61 to 282.32	168.71 pmol/L Interval 100.05 to 237.38	223.18 pmol/L Interval 150.43 to 295.92	187.66 pmol/L Interval 130.14 to 245.19
Mean Post Meal Insulin Value (Part B) Day 14, post-dinner, 3 hour	200.85 pmol/L Interval 106.15 to 295.54	167.22 pmol/L Interval 122.78 to 211.66	134.98 pmol/L Interval 85.91 to 184.05	191.01 pmol/L Interval 133.94 to 248.09	175.02 pmol/L Interval 132.2 to 217.83

PRIMARY outcome

Timeframe: Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.

Population: PD Population.

Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. Weighted mean were assessed for (0-12) and (0-24). AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=14 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=12 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Change From Baseline in Weighted Mean for Glucose Value (Part B) Weighted mean (0-12), Day 7	0.064 mmol/L Interval -0.629 to 0.756	-0.432 mmol/L Interval -1.123 to 0.259	0.555 mmol/L Interval -0.363 to 1.474	1.103 mmol/L Interval 0.424 to 1.781	-0.862 mmol/L Interval -1.812 to 0.089
Change From Baseline in Weighted Mean for Glucose Value (Part B) Weighted mean (0-12), Day 14	-0.235 mmol/L Interval -1.099 to 0.63	-0.539 mmol/L Interval -1.372 to 0.294	0.123 mmol/L Interval -0.806 to 1.052	0.656 mmol/L Interval -0.001 to 1.312	-1.039 mmol/L Interval -1.958 to -0.12
Change From Baseline in Weighted Mean for Glucose Value (Part B) Weighted mean (0-24), Day 14	-0.414 mmol/L Interval -1.134 to 0.306	-0.555 mmol/L Interval -1.463 to 0.352	0.321 mmol/L Interval -0.602 to 1.244	0.837 mmol/L Interval 0.126 to 1.548	-1.025 mmol/L Interval -1.889 to -0.161

PRIMARY outcome

Timeframe: Baseline and at pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose.

Population: PD Population

Baseline was considered to be Day -1 pre-breakfast value. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. If either the Baseline or post-randomization value was missing, the change from Baseline is set to missing as well. If measurements were taken in triplicate, then the mean of the triplicate measurements was used as the Baseline. AUC with respect to that time interval was calculated using the linear trapezoidal rule. The weighted mean was determined by dividing the AUC by the observed length of the collection interval (time of last assessment - time of first assessment in hours). In order for the AUC to be calculated, the first and last time points and at least one additional assessment falling between the two must be non-missing.

Outcome measures

Outcome measures
Measure	Part A n=14 Participants Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	GSK1292263 75 mg n=13 Participants Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days	GSK1292263 300 mg n=12 Participants Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days	GSK1292263 600 mg n=14 Participants Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=12 Participants Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Change From Baseline in Weighted Mean for Insulin Value (Part B) Weighted mean (0-12), Day 7	6.146 pmol/L Interval -12.944 to 25.236	-19.241 pmol/L Interval -39.283 to 0.801	-47.290 pmol/L Interval -89.816 to -4.764	-36.334 pmol/L Interval -67.09 to -5.578	5.979 pmol/L Interval -20.154 to 32.112
Change From Baseline in Weighted Mean for Insulin Value (Part B) Weighted mean (0-12), Day 14	21.751 pmol/L Interval 4.762 to 38.739	6.672 pmol/L Interval -15.624 to 28.968	-42.657 pmol/L Interval -91.85 to 6.535	-33.753 pmol/L Interval -61.363 to -6.143	17.328 pmol/L Interval -4.094 to 38.75
Change From Baseline in Weighted Mean for Insulin Value (Part B) Weighted mean (0-24), Day 14	22.127 pmol/L Interval 5.128 to 39.127	4.626 pmol/L Interval -15.718 to 24.97	-35.220 pmol/L Interval -70.65 to 0.209	-31.067 pmol/L Interval -65.498 to 3.363	18.848 pmol/L Interval -2.177 to 39.874

PRIMARY outcome

Timeframe: At pre-breakfast on Days -1 and 14, and then at 0.5, 1, 1.5, 2 and 3 hours post dose

Population: PD Population. No data was collected for this outcome measure.

Data was not collected for this outcome measure.

Outcome measures

Outcome data not reported

Adverse Events

Part A - GSK1292263 300 mg

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Part B - Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Part B - GSK1292263 75 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Part B - GSK1292263 300 mg

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

GSK1292263 600 mg

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Sitagliptin 50 mg

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Part A - GSK1292263 300 mg n=6 participants at risk Participants received a single dose of oral 300 mg tablet of GSK1292263 on Day 1 immediately after eating the breakfast meal. Participants also received their usual metformin monotherapy (\>=1000 mg per day).	Part B - Placebo n=14 participants at risk Participants received 3 tablets of matching placebo BID along with metformin for 14 days.	Part B - GSK1292263 75 mg n=13 participants at risk Participant received 1 tablet of 75 mg of GSK1292263 and 2 tablets of matching placebo along with metformin BID for 14 days.	Part B - GSK1292263 300 mg n=12 participants at risk Participant received 1 tablet of 200 mg, 1 tablet of 75 mg and 1 tablet of 25 mg (all GSK1292263) along with metformin BID for 14 days.	GSK1292263 600 mg n=15 participants at risk Participant received 3 tablet of 200 mg of GSK1292263 in the morning and 3 tablets of matching placebo in the evening along with metformin for 14 days.	Sitagliptin 50 mg n=13 participants at risk Participant received 50 mg of Sitagliptin BID along with metformin for 14 days.
Gastrointestinal disorders Diarrhoea	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	8.3% 1/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	20.0% 3/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Gastrointestinal disorders Nausea	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	16.7% 2/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	6.7% 1/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Gastrointestinal disorders Flatulence	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	6.7% 1/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	8.3% 1/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Gastrointestinal disorders Constipation	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Gastrointestinal disorders Vomiting	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Nervous system disorders Headache	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	14.3% 2/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	16.7% 2/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Nervous system disorders Dizziness	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	6.7% 1/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Nervous system disorders Sinus headache	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.1% 1/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Infections and infestations Infected sebaceous cyst	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Infections and infestations Oral herpes	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Infections and infestations Viral infection	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.1% 1/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	8.3% 1/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Blood and lymphatic system disorders Anaemia	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	6.7% 1/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Cardiac disorders Sinus tachycardia	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	8.3% 1/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Injury, poisoning and procedural complications Excoriation	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Investigations Heart rate increased	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Neck pain	0.00% 0/6 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/14 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/12 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	0.00% 0/15 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.	7.7% 1/13 • AEs and SAEs were reported up to 10 days after discharge (Day 2) in Part A and up to 10 days after discharge (Day 15 ) in Part B. AEs and SAEs were reported for the Safety Population which consisted of all participants enrolled in the study and who had received at least one dose of study drug.

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