Trial Outcomes & Findings for A Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 Administered With Metformin to Type 2 Diabetes Patients (NCT NCT02202161)

NCT ID: NCT02202161

Last Updated: 2017-11-06

Results Overview

The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value. It was assessed on Baseline, Day 7 and 14. Data for fasting and weighted mean (WM) AUC(0-24 hour) glucose is provided. Statistics for least square mean is provided and participants withdrawing early were excluded. Results were based on an analysis of covariance (ANCOVA) model: change from Baseline = Baseline + treatment.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 70 participants
• Primary outcome timeframe: Baseline (Day -1) and Day 14 (Fasting Pre-dose [within 15 minutes of dose], 30 minutes, 1, 1.5, 2, 4 [pre-lunch], 5.5, 10 [pre-dinner], 11.5, 14 [bed time] and 24 hours) and Day 7 (30 minutes, 2, 4 [pre-lunch], 5.5, 10 [pre-dinner], 11.5, and 24 hours)
• Results posted on: 2017-11-06

Participant Flow

The study was conducted from 27 August 2014 to 30 January 2015. After interim analysis of safety, tolerability, pharmacodynamic and/or pharmacokinetic (PK) data, GSK2330672 10 and 20 milligram (mg) doses were dropped and GSK2330672 60 mg was added.

A total of 187 participants were screened, of these, 112 were screen failures and 75 entered the run-in period. Five participants were withdrawn prior to taking a metformin dose in the 14 days of run-in period. A total of 64 participants were randomized to receive investigational product, as 6 participants were withdrawn prior to randomization.

Participant milestones

Measure	Placebo Participants were randomized to receive matching placebo solution of GSK2330672 orally twice daily (BID) for 14 days. Participants drank the contents of dosing bottle (45 milliliters \[mL\]) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Overall Study STARTED	13	5	5	9	9	10	13	6
Overall Study COMPLETED	12	4	5	9	8	9	13	0
Overall Study NOT COMPLETED	1	1	0	0	1	1	0	6

Reasons for withdrawal

Measure	Placebo Participants were randomized to receive matching placebo solution of GSK2330672 orally twice daily (BID) for 14 days. Participants drank the contents of dosing bottle (45 milliliters \[mL\]) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Overall Study Adverse Event	1	1	0	0	0	1	0	0
Overall Study Did not meet continuation criteria	0	0	0	0	0	0	0	3
Overall Study Physician Decision	0	0	0	0	0	0	0	3
Overall Study Withdrawal by Subject	0	0	0	0	1	0	0	0

Baseline Characteristics

A Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK2330672 Administered With Metformin to Type 2 Diabetes Patients

Baseline characteristics by cohort

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only n=6 Participants Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Total n=70 Participants Total of all reporting groups
Age, Continuous	52.1 Years STANDARD_DEVIATION 6.97 • n=5 Participants	54.0 Years STANDARD_DEVIATION 4.30 • n=7 Participants	56.2 Years STANDARD_DEVIATION 8.50 • n=5 Participants	57.1 Years STANDARD_DEVIATION 5.86 • n=4 Participants	55.0 Years STANDARD_DEVIATION 4.27 • n=21 Participants	54.8 Years STANDARD_DEVIATION 7.47 • n=10 Participants	53.7 Years STANDARD_DEVIATION 6.79 • n=115 Participants	55.5 Years STANDARD_DEVIATION 3.51 • n=6 Participants	54.5 Years STANDARD_DEVIATION 6.20 • n=6 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants	2 Participants n=4 Participants	6 Participants n=21 Participants	4 Participants n=10 Participants	5 Participants n=115 Participants	3 Participants n=6 Participants	31 Participants n=6 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	2 Participants n=7 Participants	1 Participants n=5 Participants	7 Participants n=4 Participants	3 Participants n=21 Participants	6 Participants n=10 Participants	8 Participants n=115 Participants	3 Participants n=6 Participants	39 Participants n=6 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	1 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	1 Participants n=6 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	3 Participants n=6 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	3 Participants n=21 Participants	0 Participants n=10 Participants	3 Participants n=115 Participants	1 Participants n=6 Participants	12 Participants n=6 Participants
Race (NIH/OMB) White	10 Participants n=5 Participants	4 Participants n=7 Participants	4 Participants n=5 Participants	8 Participants n=4 Participants	4 Participants n=21 Participants	9 Participants n=10 Participants	10 Participants n=115 Participants	5 Participants n=6 Participants	54 Participants n=6 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=6 Participants	0 Participants n=6 Participants

PRIMARY outcome

Timeframe: Baseline (Day -1) and Day 14 (Fasting Pre-dose [within 15 minutes of dose], 30 minutes, 1, 1.5, 2, 4 [pre-lunch], 5.5, 10 [pre-dinner], 11.5, 14 [bed time] and 24 hours) and Day 7 (30 minutes, 2, 4 [pre-lunch], 5.5, 10 [pre-dinner], 11.5, and 24 hours)

Population: Safety population was used which was defined as all participants enrolled into the study who received at least one dose of study drug (including GSK2330672, GSK2330672-matched placebo, sitagliptin and metformin). Only those participants available at the specified time points were analyzed.

The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value. It was assessed on Baseline, Day 7 and 14. Data for fasting and weighted mean (WM) AUC(0-24 hour) glucose is provided. Statistics for least square mean is provided and participants withdrawing early were excluded. Results were based on an analysis of covariance (ANCOVA) model: change from Baseline = Baseline + treatment.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Change From Baseline in Derived Plasma Glucose Parameter Over a 24-hour Period-fasting and Weighted Mean Glucose Area Under Curve (AUC[0-24 Hour]) Fasting, Day 14	-10.00 Mg/deciliter Standard Deviation 19.207	-22.75 Mg/deciliter Standard Deviation 11.354	-16.20 Mg/deciliter Standard Deviation 28.709	-48.67 Mg/deciliter Standard Deviation 32.650	-36.13 Mg/deciliter Standard Deviation 23.117	-40.22 Mg/deciliter Standard Deviation 19.156	-38.38 Mg/deciliter Standard Deviation 16.439	—
Change From Baseline in Derived Plasma Glucose Parameter Over a 24-hour Period-fasting and Weighted Mean Glucose Area Under Curve (AUC[0-24 Hour]) Fasting, Day 7	-6.58 Mg/deciliter Standard Deviation 16.357	-8.25 Mg/deciliter Standard Deviation 6.500	-1.40 Mg/deciliter Standard Deviation 23.050	-38.56 Mg/deciliter Standard Deviation 24.744	-34.38 Mg/deciliter Standard Deviation 19.398	-24.78 Mg/deciliter Standard Deviation 13.414	-24.54 Mg/deciliter Standard Deviation 33.955	—
Change From Baseline in Derived Plasma Glucose Parameter Over a 24-hour Period-fasting and Weighted Mean Glucose Area Under Curve (AUC[0-24 Hour]) WM AUC(0-24 hour), Day 7	3.91 Mg/deciliter Standard Deviation 20.668	-12.14 Mg/deciliter Standard Deviation 11.828	-7.01 Mg/deciliter Standard Deviation 17.262	-25.33 Mg/deciliter Standard Deviation 25.819	-21.47 Mg/deciliter Standard Deviation 18.419	-14.84 Mg/deciliter Standard Deviation 18.569	-26.63 Mg/deciliter Standard Deviation 23.610	—
Change From Baseline in Derived Plasma Glucose Parameter Over a 24-hour Period-fasting and Weighted Mean Glucose Area Under Curve (AUC[0-24 Hour]) WM AUC(0-24 hour), Day 14	-9.94 Mg/deciliter Standard Deviation 18.458	-22.44 Mg/deciliter Standard Deviation 15.928	-17.80 Mg/deciliter Standard Deviation 16.990	-37.48 Mg/deciliter Standard Deviation 32.909	-32.22 Mg/deciliter Standard Deviation 22.948	-45.54 Mg/deciliter Standard Deviation 21.010	-35.85 Mg/deciliter Standard Deviation 20.233	—

PRIMARY outcome

Timeframe: Up to 14 days (treatment period)

Population: Safety population.

An AE was defined as any untoward medical occurrence (MO) in a participant temporally associated with the use of a medicinal product (MP), whether or not considered related to the MP and can therefore be any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with its use. The SAE was any untoward MO that, at any dose, results in death, life threatening, persistent or significant disability/incapacity, results in or prolongs inpatient hospitalization, congenital abnormality or birth defect, that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition and alanine aminotransferase (ALT) >= 3× upper limit of normal (ULN) and total bilirubin >=2 × ULN (>35% direct) or ALT >=3 × ULN and international normalized ratio >1.5.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Participants With Incidence and Nature of Adverse Events (AEs) and Serious Adverse Events (SAEs) Any AE	9 Participants	4 Participants	5 Participants	5 Participants	8 Participants	8 Participants	8 Participants	—
Number of Participants With Incidence and Nature of Adverse Events (AEs) and Serious Adverse Events (SAEs) Any SAE	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Day 15

Population: Safety population

Hematology parameters included platelet, red blood cell (RBC) count, mean corpuscular volume (MCV), neutrophils, white blood cell (WBC) count (absolute), mean corpuscular hemoglobin (MCH), lymphocytes, mean corpuscular hemoglobin concentration (MCHC), monocytes, hemoglobin, eosinophils, hematocrit and basophils. It was assessed on Baseline (pre-dose Day -1), Day 7 and 15. Data for parameters with above and below the PCI is provided.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Participants With Abnormal Hematology With Potential Clinical Concern (PCI)	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Day 15

Population: Safety population.

Clinical chemistry parameters included blood urea nitrogen (BUN), potassium, aspartate aminotransferase (AST), total bilirubin, direct bilirubin, creatinine, chloride, alanine aminotransferase (ALT), uric acid, fasting glucose, total carbon dioxide, gamma glutamyltransferase (GGT), albumin, sodium, calcium, alkaline phosphatase (ALP), total protein, total carbon dioxide and triglycerides. It was assessed on Baseline (pre-dose Day -1), Day 7 and 15. Data for parameters with above and below the PCI is provided. The normal range (NR) and PCI definition for abnormal parameters are: ALT (NR: 0-44, 0-32, 2-33; PCI: >=2×upper limit of normal [ULN]); AST (NR: 0-40; PCI: >=2× ULN) and total bilirubin (NR: 0.00-20.52; PCI: >=1.5× ULN).

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Participants With Abnormal Clinical Chemistry With PCI ALT, high	1 Participants	0 Participants	2 Participants	2 Participants	2 Participants	1 Participants	1 Participants	—
Number of Participants With Abnormal Clinical Chemistry With PCI AST, high	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Clinical Chemistry With PCI Total Bilirubin, hgh	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline (pre-dose Day -1), Day 7 and 15

Population: Safety population.

Urinalysis included urine occult blood: trace to 3+, glucose: negative to 3+, protein: negative to 2+ and ketones: trace to negative by dipstick and microscopic examination included cast, cellular cast, granular cast, hyaline cast (none seen to 1) and RBC: 0-2, 3-10, 11-30, >30, WBC: none seen, 0-5, 1, 2, 4, <5, 6-10, 11-30, 19, >30). The plus sign increases with a higher level of occult blood, glucose, ketones, proteins, RBC, WBC in the urine: 1+: slightly positive, 2+: positive, 3+: high positive. Participants were categorized as none seen or 1 based on the absence or presence, respectively, of cast, cellular cast, granular cast and hyaline cast. Higher value indicates higher abnormality.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day 7, 1+	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day -1, 4	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Granular Casts, Day -1, none seen	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Glucose, Day 7, 1+	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Hyaline Casts, Day 7, None seen	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Protein, Day 15, Trace	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Protein, Day 15, 1+	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-RBC, Day -1, none seen	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-RBC, Day 7, 0-2	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-RBC, Day 7, 3-10	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day -1, none seen	2 Participants	2 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day -1, 0-5	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day 15, 2+	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 7, 1	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 7, <5	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 7, 11-30	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 7, 19	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 7, >30	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 15, 0-5	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 15, 1	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 15, 2	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 15, 4	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 15, 11-30	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 15, >30	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day -1, Trace	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day -1, small	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day-1, 3+	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day 7, Trace	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day 7, Trace intact	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day 7, small	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day 15, Trace	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Occult Blood, Day 15, small	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Casts, Day 7, none seen	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Cellular Casts, Day -1, none seen	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Cellular Casts, Day 7, none seen	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Cellular Casts, Day 15, none seen	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Granular Casts, Day 7, none seen	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Granular Casts, Day 15, none seen	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Glucose, Day -1, Trace	1 Participants	0 Participants	1 Participants	1 Participants	1 Participants	2 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Glucose, Day -1, 1+	0 Participants	0 Participants	0 Participants	3 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Glucose, Day -1, 2+	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Glucose, Day -1, 3+	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Glucose, Day 7, Trace	0 Participants	0 Participants	0 Participants	2 Participants	1 Participants	1 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Hyaline Casts, Day -1, none seen	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Hyaline Casts, Day 7, 1	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-Hyaline Casts, Day 15, none seen	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Ketones, Day 7, Trace	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Protein, Day -1, 1+	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Protein, Day 7, 2+	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-RBC, Day -1, 0-2	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-RBC, Day -1, 3-10	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-RBC, Day -1, 11-30	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-RBC, Day 7, none seen	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-RBC, Day 15, none seen	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day -1, 1	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day -1, 6-10	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day -1, 11-30	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day -1, >30	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Abnormal Urinalysis Data Urine Microscopy-WBC, Day 7, 0-5	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline (pre-dose Day -1), Day 7 and 15

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

Data for mean specific gravity is provided. Specific gravity is a measure of the amount of material dissolved in the urine. Specific gravity is the ratio of the density (mass of a unit volume) of a substance to the density (mass of the same unit volume) of a reference substance. Normal urine has a specific gravity between 1.010 and 1.020.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Summary of Urinalysis Data-mean Specific Gravity Day -1	1.0193 Ratio Standard Deviation 0.00694	1.0182 Ratio Standard Deviation 0.00581	1.0128 Ratio Standard Deviation 0.00421	1.0190 Ratio Standard Deviation 0.00618	1.0172 Ratio Standard Deviation 0.00610	1.0189 Ratio Standard Deviation 0.00780	1.0148 Ratio Standard Deviation 0.00706	—
Summary of Urinalysis Data-mean Specific Gravity Day 7	1.0196 Ratio Standard Deviation 0.00753	1.0208 Ratio Standard Deviation 0.00904	1.0184 Ratio Standard Deviation 0.00896	1.0191 Ratio Standard Deviation 0.00739	1.0194 Ratio Standard Deviation 0.00726	1.0208 Ratio Standard Deviation 0.00859	1.0160 Ratio Standard Deviation 0.00790	—
Summary of Urinalysis Data-mean Specific Gravity Day 15	1.0188 Ratio Standard Deviation 0.00403	1.0193 Ratio Standard Deviation 0.00435	1.0158 Ratio Standard Deviation 0.00259	1.0132 Ratio Standard Deviation 0.00471	1.0121 Ratio Standard Deviation 0.00348	1.0160 Ratio Standard Deviation 0.00787	1.0140 Ratio Standard Deviation 0.00815	—

PRIMARY outcome

Timeframe: Baseline (pre-dose Day -1), Day 7 and 15

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

Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0).

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Summary of Urinalysis Data-mean pH Day -1	5.73 Unit on a scale Standard Deviation 0.388	6.00 Unit on a scale Standard Deviation 0.000	6.10 Unit on a scale Standard Deviation 0.224	6.11 Unit on a scale Standard Deviation 0.220	5.83 Unit on a scale Standard Deviation 0.354	5.95 Unit on a scale Standard Deviation 0.438	5.85 Unit on a scale Standard Deviation 0.516	—
Summary of Urinalysis Data-mean pH Day 7	5.83 Unit on a scale Standard Deviation 0.389	5.90 Unit on a scale Standard Deviation 0.224	6.00 Unit on a scale Standard Deviation 0.000	5.89 Unit on a scale Standard Deviation 0.220	5.61 Unit on a scale Standard Deviation 0.486	5.95 Unit on a scale Standard Deviation 0.284	5.69 Unit on a scale Standard Deviation 0.435	—
Summary of Urinalysis Data-mean pH Day 15	5.88 Unit on a scale Standard Deviation 0.377	5.88 Unit on a scale Standard Deviation 0.250	6.00 Unit on a scale Standard Deviation 0.000	6.00 Unit on a scale Standard Deviation 0.000	5.72 Unit on a scale Standard Deviation 0.565	6.06 Unit on a scale Standard Deviation 0.167	5.88 Unit on a scale Standard Deviation 0.416	—

PRIMARY outcome

Timeframe: Up to Day 15

Population: Safety population

Single 12-lead ECGs was obtained at each time point during the study using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTc intervals. It was assessed on Baseline (pre-dose Day -1), Day 7 and 15. Participants with normal, abnormal not clinically significant and abnormal clinically significant ECG is presented.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Any Time Post-Baseline Normal	9 Participants	4 Participants	4 Participants	8 Participants	6 Participants	6 Participants	9 Participants	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Any Time Post-Baseline Abnormal not clinically significant	4 Participants	0 Participants	1 Participants	1 Participants	3 Participants	4 Participants	4 Participants	—
Number of Participants With Abnormal Electrocardiogram (ECG) Findings Any Time Post-Baseline Abnormal clinically significant	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Baseline (pre-dose Day -1) and, Day 7, 15

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

The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Change From Baseline in Vital Signs Assessments-temperature Day 7	-0.133 Degree Celsius Standard Deviation 0.2570	-0.280 Degree Celsius Standard Deviation 0.4764	0.040 Degree Celsius Standard Deviation 0.4393	0.033 Degree Celsius Standard Deviation 0.3937	0.033 Degree Celsius Standard Deviation 0.2062	0.010 Degree Celsius Standard Deviation 0.4458	0.015 Degree Celsius Standard Deviation 0.4451	—
Change From Baseline in Vital Signs Assessments-temperature Day 15	-0.208 Degree Celsius Standard Deviation 0.3370	0.025 Degree Celsius Standard Deviation 0.1708	-0.040 Degree Celsius Standard Deviation 0.2966	-0.111 Degree Celsius Standard Deviation 0.5622	0.056 Degree Celsius Standard Deviation 0.2744	-0.178 Degree Celsius Standard Deviation 0.5995	0.062 Degree Celsius Standard Deviation 0.3404	—

PRIMARY outcome

Timeframe: Baseline (pre-dose Day -1) and Day 7, 15

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

The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Change From Baseline in Vital Signs Assessments-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 7	-0.083 Millimeters of mercury Standard Deviation 6.8152	-1.600 Millimeters of mercury Standard Deviation 8.5323	-6.600 Millimeters of mercury Standard Deviation 1.9494	-1.556 Millimeters of mercury Standard Deviation 10.7948	-4.111 Millimeters of mercury Standard Deviation 4.9861	-2.700 Millimeters of mercury Standard Deviation 6.7007	-2.462 Millimeters of mercury Standard Deviation 7.6770	—
Change From Baseline in Vital Signs Assessments-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) DBP, Day 15	0.750 Millimeters of mercury Standard Deviation 6.1070	-2.750 Millimeters of mercury Standard Deviation 4.5735	1.800 Millimeters of mercury Standard Deviation 5.8481	-1.333 Millimeters of mercury Standard Deviation 9.1104	-1.667 Millimeters of mercury Standard Deviation 3.9370	-2.667 Millimeters of mercury Standard Deviation 6.3048	-0.769 Millimeters of mercury Standard Deviation 5.0852	—
Change From Baseline in Vital Signs Assessments-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 7	2.250 Millimeters of mercury Standard Deviation 8.4544	-4.000 Millimeters of mercury Standard Deviation 10.2225	-15.600 Millimeters of mercury Standard Deviation 6.1482	2.222 Millimeters of mercury Standard Deviation 17.6973	1.222 Millimeters of mercury Standard Deviation 9.1211	-4.300 Millimeters of mercury Standard Deviation 10.9245	-5.462 Millimeters of mercury Standard Deviation 10.3571	—
Change From Baseline in Vital Signs Assessments-systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) SBP, Day 15	2.167 Millimeters of mercury Standard Deviation 8.5049	-4.500 Millimeters of mercury Standard Deviation 10.4722	0.600 Millimeters of mercury Standard Deviation 11.8870	-5.111 Millimeters of mercury Standard Deviation 11.9105	-1.000 Millimeters of mercury Standard Deviation 9.3541	-2.111 Millimeters of mercury Standard Deviation 9.5321	-4.385 Millimeters of mercury Standard Deviation 9.2334	—

PRIMARY outcome

Timeframe: Baseline (pre-dose Day -1) and Day 7, 15

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

The change from Baseline was calculated by subtracting the Baseline values from the individual post-Baseline values. Baseline was defined as pre-dose Day -1 value.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Change From Baseline in Vital Signs Assessments-heart Rate Day 15	0.083 Beats per minute Standard Deviation 3.1176	0.250 Beats per minute Standard Deviation 6.3443	9.200 Beats per minute Standard Deviation 3.1937	-0.444 Beats per minute Standard Deviation 8.2932	4.889 Beats per minute Standard Deviation 7.4237	0.000 Beats per minute Standard Deviation 8.8034	1.846 Beats per minute Standard Deviation 9.1364	—
Change From Baseline in Vital Signs Assessments-heart Rate Day 7	-0.500 Beats per minute Standard Deviation 8.1296	9.200 Beats per minute Standard Deviation 8.2280	4.400 Beats per minute Standard Deviation 7.4027	0.556 Beats per minute Standard Deviation 5.2941	4.667 Beats per minute Standard Deviation 4.0620	1.400 Beats per minute Standard Deviation 7.0269	-0.769 Beats per minute Standard Deviation 6.2471	—

PRIMARY outcome

Timeframe: Up to Day 15 (administered after every in-house bowel movement)

Population: Safety population

The site staff classified participant's stools and record the date and time of occurrence after any bowel movement that occurs while participants were in residence in the clinic. BSFS is scale between type 1-7, it measured the shape of the stool, type 1: separate hard lumps, like nuts; type 2: sausage shaped but lumpy; type 3: like a sausage or snake but with cracks on its surface; type 4: like a sausage or snake, smooth and soft; type 5: soft blobs with clear cut edges; type 6: fluffy pieces with ragged edges, a mushy stool and type 7: watery, no solid pieces. Participants were discharged after they have had at least one bowel movement after the Day 14 dosing and after the investigator/designee had reviewed the Day 15 end of study questions.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Bowel Movements (Stool Frequency) as Rated Using the Bristol Stool Form Scale (BSFS) Across Days 1 to 14	15.2 Count of bowel movements Standard Deviation 9.29	28.2 Count of bowel movements Standard Deviation 17.47	38.4 Count of bowel movements Standard Deviation 10.74	35.0 Count of bowel movements Standard Deviation 18.49	37.3 Count of bowel movements Standard Deviation 30.72	35.9 Count of bowel movements Standard Deviation 21.67	15.0 Count of bowel movements Standard Deviation 10.96	—

PRIMARY outcome

Timeframe: Up to Day 15 (administered after every in-house bowel movement)

Population: Safety population. Only those participants available at the specified time points were analyzed. For each BSFS scale rating the "Number of Participants Analyzed" represents the number of participants reporting that rating not the number evaluated.

The site staff classified participant's stools and record the date and time of occurrence after any bowel movement that occurs while participants were in residence in the clinic. BSFS is scale between type 1-7, it measured the shape of the stool, type 1: separate hard lumps, like nuts; type 2: sausage shaped but lumpy; type 3: like a sausage or snake but with cracks on its surface; type 4: like a sausage or snake, smooth and soft; type 5: soft blobs with clear cut edges; type 6: fluffy pieces with ragged edges, a mushy stool and type 7: watery, no solid pieces. Participants were discharged after they have had at least one bowel movement after the Day 14 dosing and after the investigator/designee had reviewed the Day 15 end of study questions.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14 BSFS scale rating, 7 events : Events	16 Events	51 Events	47 Events	86 Events	50 Events	98 Events	10 Events	—
Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14 BSFS scale rating, 5 events : Events	30 Events	2 Events	8 Events	26 Events	9 Events	30 Events	26 Events	—
Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14 BSFS scale rating, 6 events : Events	59 Events	81 Events	113 Events	181 Events	250 Events	201 Events	70 Events	—
Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14 BSFS scale rating, 1 event : Events	2 Events	—	—	1 Events	—	1 Events	2 Events	—
Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14 BSFS scale rating, 2 events : Events	6 Events	—	2 Events	1 Events	—	—	10 Events	—
Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14 BSFS scale rating, 3 events : Events	28 Events	—	4 Events	1 Events	6 Events	5 Events	36 Events	—
Number of Events With the Rating on Quality of Stools as Rated Using the BSFS Across Days 1 to 14 BSFS scale rating, 4 events : Events	56 Events	7 Events	18 Events	19 Events	21 Events	24 Events	41 Events	—

PRIMARY outcome

Timeframe: Day 7 and 14

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

GSRS is a rating scale consisting of 15 items. Each item was scored from 1: no discomfort at all, 2: minor discomfort, 3: mild discomfort, 4: moderate discomfort, 5: moderately severe discomfort, 6: severe discomfort, 7: very severe discomfort. The overall GSRS score is the mean of these 15 items, varying from 1 to 7; a score of 1 indicates that no symptoms are present, and a score of 7 indicates the worst possible degree of all symptoms. A higher score relative to Baseline indicates worsening of severity. There were 5 defined syndrome scores and 1 overall score that was derived by computing the mean of the scores for specific subsets of questions as indicated below: abdominal pain (1, 4, 5); reflux syndrome (2, 3); diarrhea syndrome (11, 12, 14); indigestion syndrome (6, 7, 8, 9); constipation syndrome (10, 13, 15) and overall GSRS (1-15). The data is presented for participants with worsening of symptoms in >=2 levels.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Heartburn, Day 7	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Acid reflux, Day 7	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Constipation, Day 7	1 Participants	0 Participants	3 Participants	4 Participants	3 Participants	0 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Diarrhea, Day 7	0 Participants	0 Participants	2 Participants	3 Participants	4 Participants	4 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Pain/discomfort in upper abdomen, Day 7	0 Participants	0 Participants	2 Participants	2 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Hunger pains, Day 7	0 Participants	0 Participants	1 Participants	0 Participants	1 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Nausea, Day 7	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Rumbling, Day 7	1 Participants	0 Participants	2 Participants	0 Participants	1 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Bloated, Day 7	2 Participants	0 Participants	1 Participants	1 Participants	0 Participants	3 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Burping, Day 7	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Passing gas or flatus, Day 7	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Loose stools, Day 7	1 Participants	0 Participants	3 Participants	4 Participants	3 Participants	3 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Hard stools, Day 7	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Urgent need to have bowel movement, Day 7	1 Participants	0 Participants	2 Participants	1 Participants	2 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Sensatn not complete empty bowels, Day 7	0 Participants	0 Participants	2 Participants	2 Participants	3 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Abdominal pain, Day 7	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Reflux syndrome, Day 7	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Indigestion syndrome, Day 7	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Constipation syndrome, Day 7	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Diarrhea syndrome, Day 7	0 Participants	0 Participants	2 Participants	3 Participants	2 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Overall GSRS, Day 7	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Pain/discomfort in upper abdomen, Day 14	1 Participants	1 Participants	2 Participants	1 Participants	1 Participants	1 Participants	1 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Diarrhea syndrome, Day 14	0 Participants	0 Participants	3 Participants	2 Participants	1 Participants	3 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Heartburn, Day 14	1 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Acid reflux, Day 14	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Hunger pains, Day 14	0 Participants	0 Participants	2 Participants	2 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Nausea, Day 14	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Rumbling, Day 14	1 Participants	1 Participants	2 Participants	1 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Bloated, Day 14	2 Participants	1 Participants	2 Participants	1 Participants	0 Participants	3 Participants	00 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Burping, Day 14	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Passing gas or flatus, Day 14	0 Participants	1 Participants	2 Participants	2 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Constipation, Day 14	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Diarrhea, Day 14	1 Participants	0 Participants	4 Participants	3 Participants	2 Participants	5 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Loose stools, Day 14	1 Participants	1 Participants	3 Participants	2 Participants	3 Participants	3 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Hard stools, Day 14	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Urgent need to have bowel movement, Day 14	1 Participants	1 Participants	4 Participants	2 Participants	3 Participants	3 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Sensation not complete empty bowels, Day 14	0 Participants	0 Participants	3 Participants	2 Participants	3 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Abdominal pain, Day 14	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Reflux syndrome, Day 14	1 Participants	0 Participants	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Indigestion syndrome, Day 14	0 Participants	1 Participants	1 Participants	1 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Constipation syndrome, Day 14	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	2 Participants	0 Participants	—
Number of Participants With Gastrointestinal Tolerability Assessments as Rated Using the Gastrointestinal Symptom Rating Scale (GSRS; With Worsening Symptoms >=2 Levels) Overall GSRS, Day 14	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants	2 Participants	0 Participants	—

PRIMARY outcome

Timeframe: Up to Day 15

Population: Safety population

Testing cards were provided to participants for assessments. Participants with abnormal not clinically significant and abnormal clinically significant is presented. The Day -1 sample was obtained any time starting Day -2 and prior to GSK2330672 dosing on Day 1. The Day 14 sample was collected any time after dosing on Day 14 and prior to discharge on Day 15.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only n=6 Participants Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Number of Participants With Fecal Occult Blood Monitoring for Symptomatic or Visible Gastrointestinal Bleeding or Asymptomatic Occult Bleeding Abnormal not clinically significant	0 Participants	1 Participants	1 Participants	0 Participants	0 Participants	1 Participants	1 Participants	0 Participants
Number of Participants With Fecal Occult Blood Monitoring for Symptomatic or Visible Gastrointestinal Bleeding or Asymptomatic Occult Bleeding Abnormal clinically significant	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	2 Participants

SECONDARY outcome

Timeframe: Fasting pre-dose (within 15 minutes of dose), 30 minutes, 1, 1.5, 2, 3, 4 (pre-lunch), 5.5, 8, 10 hours (pre-dinner) on Day 14

Population: The PK population was used which was defined as participants from the safety population who had plasma metformin, sitagliptin, and/or GSK2330672 PK parameter estimates from any portion of the study. Only those participants available at the specified time points were analyzed.

The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data. Statistics for geometric least square mean provided.

Outcome measures

Measure	Placebo n=12 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=4 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=8 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-maximum Observed Concentration (Cmax)	1102.2 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 26.92	1289.3 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 41.81	1219.9 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 23.76	1160.0 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 18.64	1378.8 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 22.77	1376.6 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 21.70	1223.5 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 27.36	—

SECONDARY outcome

Timeframe: Fasting pre-dose (within 15 minutes of dose), 30 minutes, 1, 1.5, 2, 3, 4 (pre-lunch), 5.5, 8, 10 hours (pre-dinner) on Day 14

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

The time at which Cmax observed was determined directly from the raw concentration-time data.

Outcome measures

Measure	Placebo n=12 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=4 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=8 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-time of Occurrence of Cmax (Tmax)	1.510 Hour Interval 1.0 to 4.0	1.000 Hour Interval 1.0 to 1.5	1.000 Hour Interval 0.5 to 3.98	1.050 Hour Interval 1.0 to 1.5	1.750 Hour Interval 0.5 to 4.0	1.500 Hour Interval 1.0 to 4.0	2.050 Hour Interval 1.0 to 4.02	—

SECONDARY outcome

Timeframe: Fasting pre-dose (within 15 minutes of dose), 30 minutes, 1, 1.5, 2, 3, 4 (pre-lunch), 5.5, 8, 10 hours (pre-dinner) on Day 14

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

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

Outcome measures

Measure	Placebo n=12 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=4 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=8 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
PK Parameters for Metformin Steady State PK Parameters When Co-dosed With GSK2330672, Sitagliptin or Placebo-area Under the Concentration-time Curve Over the Dosing Interval of 10 Hours (AUC[0-10])	6805.8 Hour×ng/mL Geometric Coefficient of Variation 19.70	5982.0 Hour×ng/mL Geometric Coefficient of Variation 34.72	7066.2 Hour×ng/mL Geometric Coefficient of Variation 25.80	7066.5 Hour×ng/mL Geometric Coefficient of Variation 16.09	8090.5 Hour×ng/mL Geometric Coefficient of Variation 33.06	8375.3 Hour×ng/mL Geometric Coefficient of Variation 32.78	8425.4 Hour×ng/mL Geometric Coefficient of Variation 28.11	—

SECONDARY outcome

Timeframe: Baseline (pre-dose Day -1) and Day 7, 14

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

Data for fasting low-density cholesterol (LDL) cholesterol, high-density cholesterol (HDL) cholesterol, total cholesterol, non-HDL cholesterol and triglycerides is presented. Participants withdrawing early were excluded. Results were based on an ANCOVA model: Log(post-Baseline) - Log(Baseline) = Log(Baseline) + treatment + concomitant use of lipid lowering drugs.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides Cholesterol, Day 7	0.95 Ratio Geometric Coefficient of Variation 10.9	0.99 Ratio Geometric Coefficient of Variation 12.1	0.84 Ratio Geometric Coefficient of Variation 12.4	0.84 Ratio Geometric Coefficient of Variation 13.7	0.74 Ratio Geometric Coefficient of Variation 11.0	0.80 Ratio Geometric Coefficient of Variation 3.7	0.97 Ratio Geometric Coefficient of Variation 9.8	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides Cholesterol, Day 14	0.95 Ratio Geometric Coefficient of Variation 13.1	0.98 Ratio Geometric Coefficient of Variation 14.2	0.81 Ratio Geometric Coefficient of Variation 20.8	0.83 Ratio Geometric Coefficient of Variation 18.5	0.75 Ratio Geometric Coefficient of Variation 8.8	0.75 Ratio Geometric Coefficient of Variation 6.7	0.92 Ratio Geometric Coefficient of Variation 11.1	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides HDL cholesterol, Day 7	1.00 Ratio Geometric Coefficient of Variation 7.3	1.08 Ratio Geometric Coefficient of Variation 12.8	1.05 Ratio Geometric Coefficient of Variation 8.9	0.97 Ratio Geometric Coefficient of Variation 8.0	0.95 Ratio Geometric Coefficient of Variation 11.4	1.09 Ratio Geometric Coefficient of Variation 15.7	0.97 Ratio Geometric Coefficient of Variation 9.0	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides HDL cholesterol, Day 14	0.99 Ratio Geometric Coefficient of Variation 6.5	1.11 Ratio Geometric Coefficient of Variation 1.5	1.02 Ratio Geometric Coefficient of Variation 4.0	0.97 Ratio Geometric Coefficient of Variation 8.8	0.96 Ratio Geometric Coefficient of Variation 11.4	1.01 Ratio Geometric Coefficient of Variation 11.6	0.97 Ratio Geometric Coefficient of Variation 10.2	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides LDL cholesterol, Day 7	0.97 Ratio Geometric Coefficient of Variation 14.6	0.89 Ratio Geometric Coefficient of Variation 6.4	0.77 Ratio Geometric Coefficient of Variation 21.1	0.73 Ratio Geometric Coefficient of Variation 21.5	0.58 Ratio Geometric Coefficient of Variation 21.2	0.71 Ratio Geometric Coefficient of Variation 6.5	1.00 Ratio Geometric Coefficient of Variation 10.5	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides LDL cholesterol, Day 14	0.94 Ratio Geometric Coefficient of Variation 17.6	0.80 Ratio Geometric Coefficient of Variation 4.2	0.69 Ratio Geometric Coefficient of Variation 23.1	0.72 Ratio Geometric Coefficient of Variation 23.7	0.60 Ratio Geometric Coefficient of Variation 15.0	0.67 Ratio Geometric Coefficient of Variation 16.3	0.92 Ratio Geometric Coefficient of Variation 15.3	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides Non-HDL Cholesterol, Day 7	0.93 Ratio Geometric Coefficient of Variation 13.8	0.96 Ratio Geometric Coefficient of Variation 12.6	0.78 Ratio Geometric Coefficient of Variation 18.2	0.80 Ratio Geometric Coefficient of Variation 18.2	0.65 Ratio Geometric Coefficient of Variation 12.0	0.73 Ratio Geometric Coefficient of Variation 5.1	0.98 Ratio Geometric Coefficient of Variation 11.9	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides Non-HDL Cholesterol, Day 14	0.94 Ratio Geometric Coefficient of Variation 17.7	0.94 Ratio Geometric Coefficient of Variation 17.5	0.74 Ratio Geometric Coefficient of Variation 29.7	0.78 Ratio Geometric Coefficient of Variation 23.7	0.67 Ratio Geometric Coefficient of Variation 7.2	0.68 Ratio Geometric Coefficient of Variation 8.6	0.90 Ratio Geometric Coefficient of Variation 15.1	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides Triglycerides, Day 7	0.85 Ratio Geometric Coefficient of Variation 20.6	1.07 Ratio Geometric Coefficient of Variation 51.2	0.93 Ratio Geometric Coefficient of Variation 18.8	1.11 Ratio Geometric Coefficient of Variation 24.5	0.98 Ratio Geometric Coefficient of Variation 19.8	0.93 Ratio Geometric Coefficient of Variation 16.3	0.79 Ratio Geometric Coefficient of Variation 32.7	—
Ratio to Baseline in Fasting Low-density Cholesterol (LDL) Cholesterol, High-density Cholesterol (HDL) Cholesterol, Total Cholesterol, Non-HDL Cholesterol and Triglycerides Triglycerides, Day 14	0.85 Ratio Geometric Coefficient of Variation 23.0	1.21 Ratio Geometric Coefficient of Variation 63.3	0.96 Ratio Geometric Coefficient of Variation 35.8	1.07 Ratio Geometric Coefficient of Variation 34.3	1.00 Ratio Geometric Coefficient of Variation 16.6	1.00 Ratio Geometric Coefficient of Variation 23.7	0.74 Ratio Geometric Coefficient of Variation 34.5	—

SECONDARY outcome

Timeframe: Baseline (pre-dose Day -1) and Day 7, 14

Population: Safety population

Data for fasting apolipoprotein B is presented. Participants withdrawing early were excluded. Results were based on an ANCOVA model: Log(post-Baseline) - Log(Baseline) = Log(Baseline) + treatment + concomitant use of lipid lowering drugs.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 Participants Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 Participants Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 Participants Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 Participants Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Ratio to Baseline in Fasting Apolipoprotein B Day 7	0.97 Ratio Geometric Coefficient of Variation 10.6	0.95 Ratio Geometric Coefficient of Variation 5.9	0.78 Ratio Geometric Coefficient of Variation 13.9	0.81 Ratio Geometric Coefficient of Variation 13.1	0.69 Ratio Geometric Coefficient of Variation 12.0	0.76 Ratio Geometric Coefficient of Variation 3.8	0.96 Ratio Geometric Coefficient of Variation 10.3	—
Ratio to Baseline in Fasting Apolipoprotein B Day 14	0.93 Ratio Geometric Coefficient of Variation 14.2	0.85 Ratio Geometric Coefficient of Variation 6.7	0.75 Ratio Geometric Coefficient of Variation 19.0	0.78 Ratio Geometric Coefficient of Variation 19.6	0.67 Ratio Geometric Coefficient of Variation 14.9	0.69 Ratio Geometric Coefficient of Variation 9.3	0.88 Ratio Geometric Coefficient of Variation 15.5	—

SECONDARY outcome

Timeframe: Fasting pre-dose (within 15 minutes of dose), 1, 2, 3, 4 (pre-lunch), 10 (pre-dinner), 13 and 14 hours (bed time) on Day 14

Population: PK population.

The first occurrence of the maximum observed plasma concentration determined directly from the raw concentration-time data following the first and second dose of sitagliptin on Day 14 (Cmax1 and Cmax2).

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Sitagliptin Steady State PK Parameters When Co-dosed With Metformin-Cmax Following the First and Second Sitagliptin Doses Cmax 2	188.5 Ng/mL Geometric Coefficient of Variation 25.34	—	—	—	—	—	—	—
Sitagliptin Steady State PK Parameters When Co-dosed With Metformin-Cmax Following the First and Second Sitagliptin Doses Cmax 1	238.2 Ng/mL Geometric Coefficient of Variation 26.20	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Fasting pre-dose (within 15 minutes of dose), 1, 2, 3, 4 (pre-lunch), 10 (pre-dinner), 13 and 14 hours (bed time) on Day 14

Population: PK population.

The time at which Cmax was observed by determining directly from the raw concentration-time data following the first and second dose of sitagliptin on Day 14 (Tmax1 and Tmax2). If data permits, Tmax2 was defined as the time of Cmax following the second dose of sitagliptin.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Sitagliptin Steady State PK Parameters When Co-dosed With Metformin-Tmax Following the First and Second Sitagliptin Doses Tmax 1	2.000 Hour Interval 1.0 to 3.98	—	—	—	—	—	—	—
Sitagliptin Steady State PK Parameters When Co-dosed With Metformin-Tmax Following the First and Second Sitagliptin Doses Tmax 2	3.050 Hour Interval 2.98 to 4.07	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Fasting pre-dose (within 15 minutes of dose), 1, 2, 3, 4 (pre-lunch), 10 (pre-dinner) on Day 14

Population: PK population.

The AUC(0-10) following the first dose and prior to the second dose of sitagliptin was determined using the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations.

Outcome measures

Measure	Placebo n=13 Participants Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.	Run-in Only Participants were received open label metformin 850 mg tablet BID during run-in period, but were withdrawn prior to randomization. Participants swallowed the whole tablet with 240 mL of water and were instructed to avoid chewing or crushing.
Sitagliptin Steady State PK Parameters When Co-dosed With Metformin-AUC(0-10)	1473.5 Hour×ng/mL Geometric Coefficient of Variation 22.45	—	—	—	—	—	—	—

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

GSK2330672 10 mg BID

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

GSK2330672 20 mg BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

GSK2330672 30 mg BID

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

GSK2330672 60 mg BID

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

GSK2330672 90 mg BID

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Sitagliptin 50 mg BID

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo n=13 participants at risk Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 participants at risk Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 participants at risk Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 participants at risk Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 participants at risk Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 participants at risk Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 participants at risk Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Cardiac disorders Arrhythmia supraventricular	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.

Other adverse events

Measure	Placebo n=13 participants at risk Participants were randomized to receive matching placebo solution of GSK2330672 orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The matching placebo solution of GSK2330672, was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 10 mg BID n=5 participants at risk Participants were randomized to receive solution of GSK2330672 10 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 20 mg BID n=5 participants at risk Participants were randomized to receive solution of GSK2330672 20 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued received metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 30 mg BID n=9 participants at risk Participants were randomized to receive solution of GSK2330672 30 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 60 mg BID n=9 participants at risk Participants were randomized to receive solution of GSK2330672 60 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	GSK2330672 90 mg BID n=10 participants at risk Participants were randomized to receive solution of GSK2330672 90 mg orally BID for 14 days. Participants drank the contents of dosing bottle (45 mL) followed by 2×50 mL rinses of bottle and then an additional 95 mL water for a total volume of 240 mL consumed. The solution of GSK2330672 (2 mg/mL), was prepared by clinical staff pharmacists after reconstitution of GSK2330672 powder with phosphate buffer into amber glass bottles for administration. All dosing treatments, bottle rinses and additional water was consumed within a 15 minute period. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the whole metformin tablet with 240 mL of water and were instructed to avoid chewing or crushing.	Sitagliptin 50 mg BID n=13 participants at risk Participants were randomized to receive sitagliptin 50 mg tablet orally BID for 14 days. Participants continued to receive metformin 850 mg tablet BID throughout the study (run-in and treatment period). Participants swallowed the both whole tablets of sitagliptin and metfornin with 240 mL of water each and were instructed to avoid chewing or crushing.
Gastrointestinal disorders Diarrhoea	30.8% 4/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	40.0% 2/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	100.0% 5/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	22.2% 2/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	77.8% 7/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	60.0% 6/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	15.4% 2/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Abdominal pain	15.4% 2/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	40.0% 2/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	22.2% 2/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 2/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Flatulence	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	30.0% 3/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Faeces soft	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	22.2% 2/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 2/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Dyspepsia	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	15.4% 2/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Nausea	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	22.2% 2/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Proctalgia	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Eructation	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Gastrooesophageal reflux disease	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Vomiting	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Abdominal distension	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Gastrointestinal sounds abnormal	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Glossodynia	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Haemorrhoids	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Oral discomfort	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Gastrointestinal disorders Rectal haemorrhage	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Nervous system disorders Headache	15.4% 2/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	22.2% 2/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Nervous system disorders Dizziness	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Nervous system disorders Paraesthesia	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Investigations Alanine aminotransferase increased	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Investigations Blood pressure increased	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Investigations Blood triglycerides increased	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Investigations Liver function test abnormal	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Skin and subcutaneous tissue disorders Pruritus	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Skin and subcutaneous tissue disorders Rash	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Infections and infestations Viral infection	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	22.2% 2/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Infections and infestations Urinary tract infection	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Musculoskeletal and connective tissue disorders Musculoskeletal discomfort	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	20.0% 1/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Eye disorders Ocular hyperaemia	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Eye disorders Scleral hyperaemia	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
General disorders Feeling hot	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
General disorders Feeling jittery	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	11.1% 1/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Injury, poisoning and procedural complications Anal injury	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Injury, poisoning and procedural complications Skin abrasion	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	10.0% 1/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.
Ear and labyrinth disorders Ear discomfort	0.00% 0/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/5 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/9 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	0.00% 0/10 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.	7.7% 1/13 • AEs and SAEs were collected from run-in period until the follow-up contact (7-10 days after discharge). SAEs and non-SAE were reported from treatment period only (up to 14 days). Safety population used for assessment of safety results.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

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

Restriction type: OTHER