Conditions: Gastroparesis
Keywords: tolerability pharmacokinetics 13 C oral breath test Type I and II Diabetes mellitus gastroparesis gut motility phase II pharmacodynamics repeat dose gastric emptying symptoms GSK962040
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 79
Healthy volunteers: no

Brief summary:
GSK962040 is a novel small molecule motilin agonist. The Phase I studies (MOT107043 and MOT109681) demonstrated that single doses of GSK962040 up to 150 mg and repeat dosing of up to 125 mg/day for 14 days were well tolerated with adverse events not occurring in greater prevalence than placebo, and no significant abnormal vital sign, ECG, or clinical laboratory findings. Pharmacokinetic parameters were linear and approximately dose proportional over the range of doses administered. Single doses of 50 mg - 150 mg GSK962040 significantly increased the rate of gastric emptying up to 40% as measured by the 13C octanoic acid stable isotope breath test. A similar effect of 50 mg and 125 mg on gastric emptying was observed throughout repeated dosing to healthy volunteers for 14-days.

The aims of the present investigation (MOT114479) are to assess the pharmacodynamic effects (gastric emptying and symptoms), safety, tolerability, and pharmacokinetics of GSK962040 after 28 days of once-daily dosing in Type I and Type II diabetic subjects with gastroparesis. An additional aim is to characterize the dose/exposure - pharmacodynamic effect relationship.

Detailed description:

Arms:
arm 1: GSK962040 10 mg arm 2: GSK962040 50 mg arm 3: GSK962040 125 mg arm 4: Placebo

Interventions: intervention 1: GSK962040 (5 mg tablet) intervention 2: GSK962040 (25 mg tablet) intervention 3: GSK962040 (125 mg tablet) intervention 4: Placebo
Intervention descriptions: intervention 1: 5 mg tablet intervention 2: 25 mg tablet intervention 3: 125 mg tablet intervention 4: matching placebo tablet

Protocol document: