Conditions: Diabetes Mellitus, Type 2
Keywords: pharmacokinetic intestinal bile acid transporter inhibitor metformin sitagliptin GSK2330672 pharmacodynamic
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 70
Healthy volunteers: no

Brief summary:
This study is being conducted to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of GSK2330672 compared to sitagliptin when administered with metformin for 14 days to subjects with type 2 diabetes mellitus (T2DM). Approximately 72 male and female subjects aged 30-64 years with T2DM and currently taking metformin will be recruited for this study. Eligible subjects will begin a run-in period of 13-15 days to stabilize on metformin 850 milligram (mg) twice a day (BID). Subjects will then be randomized to GSK2330672 10 mg, 20 mg, 30 mg, 90 mg, matching placebo or open-label sitagliptin 50 mg for 14 days BID. Subjects will return for a follow-up visit 7-10 days after discharge.

Detailed description:

Arms:
arm 1: Subjects will receive metformin 850 mg BID for 13-15 days during the run in period followed by GSK2330672 10 mg BID for 14 days. arm 2: Subjects will receive metformin 850 mg BID for 13-15 days during the run in period followed by GSK2330672 20 mg BID for 14 days. arm 3: Subjects will receive metformin 850 mg BID for 13-15 days during the run in period followed by GSK2330672 30 mg BID for 14 days. arm 4: Subjects will receive metformin 850 mg BID for 13-15 days during the run in period followed by GSK2330672 90 mg BID for 14 days. arm 5: Subjects will receive metformin 850 mg BID for 13-15 days during the run in period followed by matching placebo (of GSK2330672) BID for 14 days. arm 6: Subjects will receive metformin 850 mg BID for 13-15 days during the run in period followed by Sitagliptin 50 mg BID for 14 days. In this study, sitagliptin 50 mg BID will be provided as open-label (unblinded) study treatment.

Interventions: intervention 1: GSK2330672 intervention 2: Placebo intervention 3: Sitagliptin intervention 4: Metformin
Intervention descriptions: intervention 1: GSK2330672 will be available in 10 mg, 20 mg, 30 mg, and 90 mg oral solution to be administered BID for 14 days. Subjects are to drink contents of dosing bottle (45 ml) followed by 2 x 50 ml rinses of bottle and then an additional 95 ml water for a total volume of 240 ml consumed intervention 2: Matching placebo will be available as oral solution to be administered for 14 days, BID. Subjects are to drink contents of dosing bottle (45 ml) followed by 2 x 50 ml rinses of bottle and then an additional 95 ml water for a total volume of 240 ml consumed intervention 3: Sitagliptin will be available as film-coated tablets Tablet of 50 mg to be administered orally, BID, for 14 days intervention 4: Metformin will be available as 850 mg white to off-white, film-coated tablets; to be administered BID orally during run-in through Day 14

Protocol document: