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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
49
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.
Hammersmith Medicines Research
London, United Kingdom
Pharmacodynamic parameters: gastric pH and plasma gastrin
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.
Time frame: 8 weeks
Clinically relevant changes from baseline in safety assessments
Physical examination, ECG and safety tests of blood/urine at screening and at follow up.
Time frame: 8 weeks
Numbers of adverse events
Adverse events throughout study.
Time frame: 8 weeks
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