GSK962040 is a selective non-peptide motilin receptor agonist which is in development for the
treatment of conditions associated with slow rates of gastric emptying. Single ascending
doses (1 to 150 mg), and 14-days repeated doses (10 to 125 mg daily) have been investigated
in two randomized, placebo-controlled trials. Results show that these doses were well
tolerated with few mild to moderate adverse events (AE), and no clinically significant
abnormal vital sign measurements, ECG changes or abnormal clinical laboratory findings.
GSK962040 exhibited predictable PK with and without food. The mean within subject time for
half a [13C]-containing meal to empty from the stomach (GE t½) decreased by 22-43% from
placebo with GSK962040 50-150 mg single doses, and shortening of gastric emptying was
confirmed at doses of 50 mg and above in the repeat dose study.
Several studies have shown that motilin agonists increase lower oesophageal sphincter (LOS)
pressure and have various dose dependent effects on oesophageal peristaltic amplitudes and
propulsive contractions in both healthy volunteers and patients with gastro-oesophageal
reflux disease (GORD). The purpose of the present study is to examine the effect of GSK962040
on oesophageal function, using techniques such as high resolution oesophageal manometry, and
pH/gastric transit using a wireless motility capsule.