The objectives of this study were: To compare repeated doses of YF476 at 2 dose levels, placebo and omeprazole with respect to their effect on basal- and food- stimulated gastric pH in healthy volunteers. To compare repeated doses of YF476 at 2 dose levels, placebo and omeprazole with respect to their effect on basal and meal stimulated pH. To assess the safety, tolerability and pharmacokinetics of repeated doses of YF476 in healthy volunteers.
YF476 is clearly a potent and selective gastrin/CCK-B antagonist and should inhibit basal and meal-stimulated gastric acid secretion, enhance gastric emptying of a liquid meal and increase lower oesphageal sphincter pressure in man. Therefore YF476 might benefit patients with reflux oesophagitis. YF476 has been well tolerated in healthy volunteers at single doses up to 100mg and remarkably well tolerated at repeat doses in animals up to 350 times the maximum dose planned for the proposed study. A range of doses of YF476 (25 and 100mg twice daily) will be administered to steady state. 24-hour ambulatory gastric pH will be monitored via an intragastric pH electrode to assess the effect of YF476 on basal and meal stimulated gastric pH. 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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
DOUBLE
Enrollment
49
There were 4 treatments as follows: YF476 25mg twice daily, YF476 100mg twice daily, placebo and omeprazole 20mg once daily. Each treatment was taken by mouth for 7 days. Each subject took 1 of the 4 treatments.
There were 4 treatments as follows: YF476 25mg twice daily, YF476 100mg twice daily, placebo and omeprazole 20mg once daily. Each treatment was taken by mouth for 7 days. Each subject took 1 of the 4 treatments.
Hammersmith Medicines Research
London, United Kingdom
Pharmacodynamic measurements: continuous 24h ambulatory gastric pH and 24 h plasma gastrin
Recording started 0.5 h before the morning dose on Study Day 7 for measurement of gastric pH; meals taken at 4, 9, 13 \& 22 h after the morning dose. Frequent blood samples for measurement of plasma gastrin.
Time frame: 6 weeks
Assessment of safety and tolerability
Physical examination, ECG and safety tests of blood/urine at screening, after the last dose and at follow up.
Time frame: 6 weeks
Pharmacokinetic analysis of plasma YF476 concentrations
Blood samples (8 mL) for assay of YF476 taken before each morning dose on Study Days 1-6 and at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 12.25, 12.5, 12.75, 13, 14.5, 15, 16, 17, 18, 20, 22 and 24h on Study Day 7 (where 0h is the time of the morning dose and 12h is the time of the evening dose)for calculation of Cmax, Tmax, AUC 0-24 h, T1/2.
Time frame: 6 weeks
Number of adverse events
Adverse events throughout the study
Time frame: 6 weeks
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.