Effect of Single Doses of YF476 on Stomach Acidity Compared With Ranitidine and Placebo in Fasted and Fed States

NCT01538797 | Completed Phase 1

• 1 other identifier: 96-016
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Reflux Oesophagitis

Keywords

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

Outcome Measures

Primary Outcomes (4)

• Clinically relevant changes from baseline in safety assessments

  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.

  6 weeks

• Numbers of adverse events

  Adverse events throughout the study

  6 weeks

• Pharmacokinetic parameters: Cmax, Tmax, AUC 0-24 h, T1/2

  Blood samples (8mL) before and at 0.5, 1, 2, 4, 6, 8, 12 and 24h after each dose for assay of YF476.

  6 weeks

• Pharmacodynamic parameters: continuous 24 h ambulatory gastric pH

  Recording starts 0.5h before dosing on each Treatment Day; meals taken at 4, 9, 13 \& 22h after dosing.

  6 weeks

Interventions

YF476 DRUG

There were 5 treatments: 3 dose levels of YF476 (5, 25 and 100 mg), placebo and ranitidine 150 mg. There were at least 7 days between consecutive Treatment Days.

Ranitidine DRUG

There were 5 treatments: 3 dose levels of YF476 (5, 25 and 100mg), placebo and ranitidine 150mg. There were at least 7 days between consecutive Treatment Days.

Eligibility Criteria

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

You may qualify if:

• Male or female and 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, NW10 7EW, United Kingdom

Location

Related Publications (1)

• Boyce M, David O, Darwin K, Mitchell T, Johnston A, Warrington S. Single oral doses of netazepide (YF476), a gastrin receptor antagonist, cause dose-dependent, sustained increases in gastric pH compared with placebo and ranitidine in healthy subjects. Aliment Pharmacol Ther. 2012 Jul;36(2):181-9. doi: 10.1111/j.1365-2036.2012.05143.x. Epub 2012 May 20.

  PMID: 22607579 DERIVED

MeSH Terms

Conditions

Esophagitis, Peptic

Interventions

YF 476; Ranitidine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Furans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Malcolm J Boyce, FRCP FFPM

  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: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2012
• First Posted: February 24, 2012
• Study Start: July 1, 1996
• Primary Completion: August 1, 1996
• Study Completion: August 1, 1996
• Last Updated: February 24, 2012

Record last verified: 2012-02

Locations

GB (1)