Effect of Repeated Doses of YF476, Omeprazole and Placebo on Stomach Acidity in Healthy Volunteers

Reflux Oesophagitis Clinical Trial

Official title:

YF476: Effects of Repeated Dosing at 2 Dose Levels on 24-hour Ambulatory Gastric pH Compared With Placebo and Omeprazole in Healthy Volunteers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01599858
• Other study ID #: 96-018
• Status: Completed
• Phase: Phase 1
• First received: May 10, 2012
• Last updated: May 14, 2012
• Start date: August 1996
• Est. completion date: October 1996

Study information

• Verified date: May 2012
• Source: Trio Medicines Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 49
• Est. completion date: October 1996
• Est. primary completion date: October 1996
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Male or female aged 18-45 years.

• No clinically relevant abnormal findings in the clinical history or physical examination at the screening assessment which could interfere with the objectives of the study or make the subject's participation hazardous.

• No clinically relevant abnormal laboratory values at the screening evaluation (Attachment 2).

• A normal ECG at the screening examination.

• A body mass index (Quetelet index) in the range 19-30:

Body Mass Index = weight [kg]_ height [m]2

• Normal blood pressure and heart rate at the screening examination, i.e. BP 90-150mmHg systolic, 40-95mmHg diastolic; heart rate 40-100 beats/min in seated position.

• Subjects must be of sufficient intelligence to understand the nature of the study and any hazards of their participation in it. They must be able to communicate satisfactorily with the Investigator and to participate in, and comply with the requirements of, the entire study.

• Subjects must give their written consent to participate after reading the Information-for-Volunteers Leaflet and Consent Form, and after having the opportunity to discuss the study with the Investigator or his deputy.

Exclusion Criteria:

• Females who are pregnant or lactating, or who are sexually active and are not using a reliable method of contraception.

• Clinically relevant abnormal history or physical findings at the screening assessment, which could interfere with the objectives of the study or the safety of the subject's participation.

• Clinically relevant abnormalities of laboratory values or ECG at screening evaluation.

• Presence of acute or chronic illness or history of chronic illness sufficient to invalidate subject's participation in the study or make it unnecessarily hazardous.

• Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease or history of any psychotic mental illness.

• Participation in other clinical studies of a new chemical entity or a prescription medicine within the previous 3 months.

• Presence or history of drug or alcohol abuse, or intake of more than 40 units of alcohol weekly.

• Loss of more than 400mL blood during the 3 months before the study, e.g. as a blood donor.

• Use of prescription medication during 30 days before the study.

• Use of an over-the-counter medicine during 7 days before the study

• Blood pressure or heart rate outside those values specified under inclusion criterion (f).

• Possibility that the subject will not cooperate with the requirements of the protocol.

• Evidence of drug abuse on urine testing at study entry.

• Positive test for hepatitis B or C or HIV 1 & 2.

• High risk of hepatitis or HIV infection.

• History of severe allergic disease.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Esophagitis
• Esophagitis, Peptic
• Reflux Oesophagitis

Intervention

Drug:
• YF476
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.
• Omeprazole
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.

Locations

Country	Name	City	State
United Kingdom	Hammersmith Medicines Research	London

Sponsors (2)

Lead Sponsor	Collaborator
Trio Medicines Ltd.	Ferring Pharmaceuticals

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	6 weeks	Yes
Primary	Assessment of safety and tolerability	Physical examination, ECG and safety tests of blood/urine at screening, after the last dose and at follow up.	6 weeks	Yes
Primary	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.	6 weeks	Yes
Primary	Number of adverse events	Adverse events throughout the study	6 weeks	Yes