Effect of 5, 10 or 25 mg of YF476 Daily for 14 Days on Stomach Acidity in Healthy Volunteers
The objective of the study was to assess whether the tolerance to the effect of YF476 on gastric pH observed with repeated doses in a previous study in healthy volunteers can be avoided by using smaller doses of YF476.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
|Official Title:||A Double-blind, Placebo-controlled, Parallel-group Study of the Effect of 5, 10 and 25 mg Daily of YF476 for 14 Days on 24-hour Ambulatory Gastric pH and Plasma Gastrin Concentrations in Healthy Volunteers|
- Pharmacodynamic parameters: gastric pH and plasma gastrin [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
On Study Days 1, 7 and 14, ambulatory gastric pH recorded continuously from 0.5h before dosing until 24h after dosing. Subjects dosed between 0900-0930h. Standard meals and a drink (decaffeinated) taken at 4, 9, 13 and 22 h after dosing. Water (150mL) given at 2, 6, 8 and 11 h after dosing.
On Study Days 1, 7 and 14, blood samples (4mL) taken via a cannula for assay of plasma gastrin at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 20, 22 and 24 h after dosing.
- Clinically relevant changes from baseline in safety assessments [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]Physical examination, ECG and safety tests of blood/urine at screening and at follow up.
- Numbers of adverse events [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]Adverse events throughout study.
|Study Start Date:||April 1997|
|Study Completion Date:||June 1997|
|Primary Completion Date:||June 1997 (Final data collection date for primary outcome measure)|
There were 4 treatments: 3 dose levels of YF476 (5mg, 10mg, 25 mg) and placebo.
Each treatment taken by mouth once daily for 14 days (Study Days 1-14). Each subject took 1 of the 4 treatments.
YF476 is a novel, potent and selective gastrin antagonist that inhibits basal and meal-stimulated gastric acid secretion, enhances gastric emptying of a liquid meal and increases lower oesophageal sphincter pressure in animals. In a placebo- and ranitidine-controlled, crossover study in healthy volunteers, single doses of 5, 25 and 100mg of YF476 increased gastric pH; the effect was dose-dependent in magnitude and duration and compared favourably with that of ranitidine 150mg. In a placebo- and omeprazole-controlled, parallel-group study in healthy volunteers, 25 and 100mg of YF476 twice daily for 7 days, did not significantly affect gastric pH unlike omeprazole 20mg daily for 7 days. YF476 and omeprazole both increased plasma gastrin concentrations. Single and repeated doses of YF476 were well tolerated.