Effect of Single Doses of YF476 on Stomach Acidity Compared With Ranitidine and Placebo in Fasted and Fed States
The objectives of the study were:
- To compare a single dose of YF476 at 3 dose levels, placebo and ranitidine with respect to their effects on basal- and food- stimulated gastric pH in healthy volunteers.
- To assess whether there is a relationship between the pharmacokinetics of YF476 and gastric pH in healthy volunteers.
- To assess the safety and tolerability of single doses of YF476 in healthy volunteers.
|Study Design:||Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
|Official Title:||YF476: Effects of a Single Dose at 3 Dose Levels on 24-hour Ambulatory Gastric pH Compared With Placebo and Ranitidine in Healthy Volunteers|
- Clinically relevant changes from baseline in safety assessments [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]Physical examination, ECG and safety tests of blood/urine at screening, 24h after dosing on each Treatment Day and at follow up. Blood pressure and heart rate before and at 0.5, 1, 2, 4, 6, 8, 12 and 24h after dosing on each Treatment Day.
- Numbers of adverse events [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]Adverse events throughout the study
- Pharmacokinetic parameters: Cmax, Tmax, AUC 0-24 h, T1/2 [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]Blood samples (8mL) before and at 0.5, 1, 2, 4, 6, 8, 12 and 24h after each dose for assay of YF476.
- Pharmacodynamic parameters: continuous 24 h ambulatory gastric pH [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]Recording starts 0.5h before dosing on each Treatment Day; meals taken at 4, 9, 13 & 22h after dosing.
|Study Start Date:||July 1996|
|Study Completion Date:||August 1996|
|Primary Completion Date:||August 1996 (Final data collection date for primary outcome measure)|
YF476 is clearly a potent and selective gastrin/CCK-B antagonist and should inhibit basal and meal-stimulated gastric acid secretion and enhance gastric emptying of a liquid meal in man. Therefore YF476 might benefit patients with reflux oesophagitis. The compound has been well tolerated in animal toxicity studies at doses in excess of the projected therapeutic dose in patients, and merits studies in healthy volunteers. Extrapolation from data obtained in animals suggests that a single oral dose of about 10mg of YF476 should compare favourably with an oral dose of 150mg of ranitidine in man with respect to effect on basal and food-stimulated gastric acid secretion. Therefore in the proposed study a range of doses of YF476 encompassing that dose will be studied; the exact dose of YF476 will be chosen on the basis of the previous study but the top dose will not exceed 100mg. 24-hour ambulatory gastric pH will be monitored via an intragastric pH electrode (7-10). Although there is variability between subjects with respect to the effects of food and drug treatment on gastric pH, the methodology for measurement of ambulatory gastric pH is robust.
|Hammersmith Medicines Research|
|London, United Kingdom, NW10 7EW|
|Study Director:||Malcolm J Boyce, FRCP FFPM||Trio Medicines Limited|