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

NCT01599858 | Completed Phase 1

• 1 other identifier: 96-018
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Reflux Oesophagitis

Keywords

YF476; gastrin receptor antagonist; gastric pH; healthy subjects; omeprazole

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• Number of adverse events

  Adverse events throughout the study

  6 weeks

Interventions

YF476 DRUG

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 DRUG

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.

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Trio Medicines Ltd.: lead
• Ferring Pharmaceuticals: collaborator

Study Sites (1)

Hammersmith Medicines Research

London, United Kingdom

Location

MeSH Terms

Conditions

Esophagitis, Peptic

Interventions

YF 476; Omeprazole

Condition Hierarchy (Ancestors)

Esophagitis; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Gastroenteritis; Peptic Ulcer; Duodenal Diseases; Intestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Malcolm Boyce

  Trio Medicines Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2012
• First Posted: May 16, 2012
• Study Start: August 1, 1996
• Primary Completion: October 1, 1996
• Study Completion: October 1, 1996
• Last Updated: May 16, 2012

Record last verified: 2012-05

Locations

GB (1)