A Randomized, Double-Blind, Placebo-Controlled Multicenter Phase II Study to Evaluate the Safety and Efficacy and Dose Response of 28 Days of Once-Daily Dosing of the Oral Motilin Receptor Agonist GSK962040, in Type I and II Diabetic Male and Female Subjects With Gastroparesis

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.