NCT01601418

Effect of Single Doses of YF476 on Stomach Acidity

Double-blind, Placebo-controlled, Single-dose, 5-way Crossover Study of the Effect of YF476 (1, 5, 25 & 100 mg) on Pentagastrin-induced Gastric Acid Output in Healthy Volunteers

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Trio Medicines Ltd. · Industry
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

The objective of the study was to assess the effect of a range of single oral doses of YF476 on pentagastrin-induced gastric acid output in healthy volunteers

Detailed description

The rationale for the study was as follows. On the basis of the pre-clinical studies, the original target disease for YF476 was gastro-oesophageal reflux disease (GORD), not only because of the excellent anti-secretory activity of YF476 but also because of its potential for increasing gastric emptying. But loss of the anti-secretory effect of YF476 in healthy subjects after repeated dosing excludes its use as an anti-secretory agent in patients with GORD. However, there is some evidence from within our repeated-dose studies in healthy subjects that gastrin receptors are blocked despite loss of the anti-secretory activity of YF476. Further evidence that repeated doses of YF476 cause sustained blockade of gastrin receptors comes from several types of study in animals. First, in the 13-week toxicology studies, all dose levels of YF476 reduced the ECL population, unlike other anti-secretory agents, histamine H2-antagonists and proton-pump inhibitors, which increase the ECL population. Second, YF476 at doses of 0.1 and 1.0 mg/kg subcutaneously twice daily for 14 days in rats abolished the increase in gastric output induced by pentagastrin on Days 1, 7 and 14. This protocol describes a study in healthy subjects using inhibition of pentagastrin-induced gastric acid output as a surrogate marker of efficacy of YF476. Pentagastrin has been used for many years to test gastric function in healthy subjects and patients. Intravenous infusion of 0.6 micrograms/kg/hour is a submaximal and well-tolerated dose.

Conditions

• Hypergastrinaemia

Interventions

Type	Name	Description
DRUG	YF476	Each subject took one capsule of YF476 (1, 5, 25 or 100 mg) or placebo on five separate occasions. Each capsule was taken with water 150 mL.
DRUG	Placebo	Each subject took one capsule of YF476 (1, 5, 25 or 100 mg) or placebo on five separate occasions. Each capsule was taken with water 150 mL.

Timeline

• Start date: 2001-10-01
• Primary completion: 2002-01-01
• Completion: 2002-01-01
• First posted: 2012-05-18
• Last updated: 2012-05-18

Locations

1 site across 1 country: United Kingdom