Effect of Repeated Doses of YF476 on Stomach Acidity

NCT01601405 | Completed Phase 1

• 1 other identifier: 01-023
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of the study were:

1. 1.To show that a single dose of YF476 blocks gastrin receptors in healthy subjects
2. 2.To show that YF476 retains its ability to block gastrin receptors after repeated dosing despite losing its ability to suppress gastric acidity.

Conditions

Hypergastrinaemia

Keywords

YF476; gastrin receptor antagonist; gastrin; gastric aspiration; healthy subjects

Outcome Measures

Primary Outcomes (6)

• Safety of YF476

  Assessed by by physical examinations, safety tests of blood and urine, ECG variables

  4 weeks

• Tolerability of YF476

  Assessed by adverse events

  4 weeks

• Pharmacokinetic analysis of plasma YF476 concentrations

  On Study Days 1 and 7, blood samples taken at 90 and 210 minutes after the start of gastric aspiration. On Study Day 14, a blood sample taken at 90 minutes only. Plasma separated and stored for subsequent assay of YF476, if deemed necessary.

  4 weeks

• Pharmacodynamic measurement for assay of volume, pH and total acidity of gastric aspirate

  On Study Days 0, 1, 7 \& 14: volume, pH and total acidity of gastric aspirate measured at 15-min intervals from 0-30 \& 90-210 min after the start of gastric aspiration

  4 weeks

• Pharmacodynamic measurement for assay of pancreastatin and pancreatic polypeptides

  On Study Days 0, 1, 7 \& 14: blood samples taken at about -30 min before the start of gastric aspiration, just before the introduction of nasogastric tube. Serum separated and stored for subsequent assay of pancreastatin, pancreatic polypeptide, and any other gastro-intestinal hormone (if necessary)

  4 weeks

• Pharmacodynamic measurement for assay of gastrin

  On Study Days 0, 1, 7 \& 14: blood samples taken at 90 min after the start of gastric aspiration. Serum separated and stored for subsequent assay of gastrin, if necessary

  4 weeks

Interventions

YF476 DRUG

Each subject took one capsule of YF476 100 mg twice daily on Days 1-6 and once on Day 7. Each capsule taken with water 150 mL.

Placebo DRUG

On Days 0 and 14, each subject took a placebo capsule. Each capsule taken with water 150 mL.

Eligibility Criteria

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

You may qualify if:

• Healthy male or female volunteers.
• Aged 18-45 years.
• A body mass index (Quetelet index) in the range 18.0-30.9.
• Women at risk of pregnancy must use a reliable method of contraception.
• 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 volunteer's participation hazardous.
• No clinically relevant abnormal laboratory values at the screening evaluation, including a normal ECG.
• Sufficient intelligence to understand the nature of the study and any hazards of participating in it. Ability to communicate satisfactorily with the investigator and to participate in, and comply with the requirements of, the entire study.
• Willingness to give written consent to participate after reading the Consent Form, and after having the opportunity to discuss the study with an investigator or his deputy.

You may not qualify if:

• Women who are pregnant or lactating.
• Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-study screening assessment that could interfere with the objectives of the study or the safety of the volunteer.
• Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the volunteer's participation in the study or make it unnecessarily hazardous.
• Positive test for Helicobacter pylori.
• Impaired endocrine, thyroid, hepatic, respiratory or renal function, diabetes mellitus, coronary heart disease, or history of any psychotic mental illness.
• Presence or history of severe adverse reaction to any drug or a history of severe allergic disease.
• Use of a prescription medicine (except oral contraceptives in females) during the 30 days before the study or use of an over-the-counter medication, with the exception of paracetamol, during the 7 days before the study.
• Participation in other clinical studies of a new chemical entity or a prescription medicine within the previous 3 months.
• Smokers.
• Presence or history of drug or alcohol abuse, or intake of more than 28 units of alcohol weekly (for men) or 21 units of alcohol weekly (for women).
• Blood pressure and heart rate in seated position at the screening examination outside the ranges 90-160 mm Hg systolic, 40-95 mm Hg diastolic; heart rate 40\_100 beats/min.
• Possibility that the volunteer will not cooperate with the requirements of the protocol.
• Evidence of drug abuse on urine testing.
• Positive test for hepatitis B, hepatitis C, HIV1 or HIV2.
• Loss of more than 400 mL blood during the 3 months before the study, e.g. as a blood donor.

Sponsors & Collaborators

• Trio Medicines Ltd.: lead
• James Black Foundation: collaborator

Study Sites (1)

Hammersmith Medicines Research

London, United Kingdom

Location

MeSH Terms

Interventions

YF 476

Study Officials

• Malcolm Boyce

  Trio Medicines Limited

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2012
• First Posted: May 18, 2012
• Study Start: October 1, 2001
• Primary Completion: November 1, 2001
• Study Completion: November 1, 2001
• Last Updated: May 18, 2012

Record last verified: 2012-05

Locations

GB (1)