Effect of GSK962040 on Oesophageal Function
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.
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
|Official Title:||A Double Blind Randomised Placebo Controlled Two Way Cross Over Study to Determine the Effect of GSK962040 on Oesophageal Function and Gastric Emptying in Healthy Male Volunteers.|
- Change from baseline lower oesophageal sphincter (LOS) pressure (including pre and post prandial measures [ Time Frame: Baseline and at 1hr30 and 2hr15mins post dose ]
- Change from baseline oesophageal peristaltic amplitudes [ Time Frame: baseline and at 1hr30min and 2hr15mins post dose ]
- Change from baseline oesophageal peristaltic velocity. [ Time Frame: baseline and at 1hr30min and 2hr15mins post dose ]
- Change from baseline proximal gastric pressure. [ Time Frame: baseline and at 1hr30min and 2hr15mins post dose ]
- Total gastric emptying time. [ Time Frame: absolute transit time measured using SmartPill ]
- Number and proximal extent of reflux episodes [ Time Frame: 24hrs ]
- Safety and tolerability of GSK962040 [ Time Frame: baseline and at selected timepoints up to 24hrs post dose ]We will monitor ECG, vital signs, safety bloods and adverse events periodically throughout the study
- Post prandial gastric and oesophageal pH [ Time Frame: 2hr15mins post dose ]
|Actual Study Start Date:||August 31, 2010|
|Study Completion Date:||October 22, 2010|
|Primary Completion Date:||October 22, 2010 (Final data collection date for primary outcome measure)|
The subjects will be administered GSK962040 125 mg tablet as a single dose on Day 1 of study treatment visit. After 2 hours, the subjects will be administered wireless motility capsule. The subjects will be observed for expulsion of WMC in stool. Each subject will attend the clinical unit for two study treatment visits which will be separated by at least one week.
Placebo Comparator: Placebo
The subjects will be administered placebo tablet as a single dose on Day 1 of study treatment visit. After 2 hours, the subjects will be administered wireless motility capsule. The subjects will be observed for expulsion of WMC in stool. Each subject will attend the clinical unit for two study treatment visits which will be separated by at least one week.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01366560
|GSK Investigational Site|
|Cambridge, United Kingdom, CB2 2GG|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|