Effect of 5, 10 or 25 mg of YF476 Daily for 14 Days on Stomach Acidity in Healthy Volunteers

This study has been completed.
Sponsor:
Collaborator:
Ferring Pharmaceuticals
Information provided by (Responsible Party):
Trio Medicines Ltd.
ClinicalTrials.gov Identifier:
NCT01597674
First received: May 10, 2012
Last updated: May 11, 2012
Last verified: May 2012
  Purpose

The objective of the study was to assess whether the tolerance to the effect of YF476 on gastric pH observed with repeated doses in a previous study in healthy volunteers can be avoided by using smaller doses of YF476.


Condition Intervention Phase
Reflux Oesophagitis
Drug: YF476
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: A Double-blind, Placebo-controlled, Parallel-group Study of the Effect of 5, 10 and 25 mg Daily of YF476 for 14 Days on 24-hour Ambulatory Gastric pH and Plasma Gastrin Concentrations in Healthy Volunteers

Further study details as provided by Trio Medicines Ltd.:

Primary Outcome Measures:
  • Pharmacodynamic parameters: gastric pH and plasma gastrin [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]

    On Study Days 1, 7 and 14, ambulatory gastric pH recorded continuously from 0.5h before dosing until 24h after dosing. Subjects dosed between 0900-0930h. Standard meals and a drink (decaffeinated) taken at 4, 9, 13 and 22 h after dosing. Water (150mL) given at 2, 6, 8 and 11 h after dosing.

    On Study Days 1, 7 and 14, blood samples (4mL) taken via a cannula for assay of plasma gastrin at 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 16, 18, 20, 22 and 24 h after dosing.


  • Clinically relevant changes from baseline in safety assessments [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Physical examination, ECG and safety tests of blood/urine at screening and at follow up.

  • Numbers of adverse events [ Time Frame: 8 weeks ] [ Designated as safety issue: Yes ]
    Adverse events throughout study.


Enrollment: 49
Study Start Date: April 1997
Study Completion Date: June 1997
Primary Completion Date: June 1997 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: YF476

    There were 4 treatments: 3 dose levels of YF476 (5mg, 10mg, 25 mg) and placebo.

    Each treatment taken by mouth once daily for 14 days (Study Days 1-14). Each subject took 1 of the 4 treatments.

Detailed Description:

YF476 is a novel, potent and selective gastrin antagonist that inhibits basal and meal-stimulated gastric acid secretion, enhances gastric emptying of a liquid meal and increases lower oesophageal sphincter pressure in animals. In a placebo- and ranitidine-controlled, crossover study in healthy volunteers, single doses of 5, 25 and 100mg of YF476 increased gastric pH; the effect was dose-dependent in magnitude and duration and compared favourably with that of ranitidine 150mg. In a placebo- and omeprazole-controlled, parallel-group study in healthy volunteers, 25 and 100mg of YF476 twice daily for 7 days, did not significantly affect gastric pH unlike omeprazole 20mg daily for 7 days. YF476 and omeprazole both increased plasma gastrin concentrations. Single and repeated doses of YF476 were well tolerated.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Males 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 19.0-30.9:

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

  • 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:

  • 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 and heart rate in seated position at the screening examination outside the ranges 90-150mmHg systolic, 40-90mmHg diastolic; heart rate 40-100 beats/min.
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01597674

Locations
United Kingdom
Hammersmith Medicines Research
London, United Kingdom
Sponsors and Collaborators
Trio Medicines Ltd.
Ferring Pharmaceuticals
Investigators
Study Director: Malcolm Boyce Trio Medicines Limited
  More Information

No publications provided

Responsible Party: Trio Medicines Ltd.
ClinicalTrials.gov Identifier: NCT01597674     History of Changes
Other Study ID Numbers: 97-010
Study First Received: May 10, 2012
Last Updated: May 11, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Trio Medicines Ltd.:
YF476
gastrin receptor antagonist
gastric pH
gastrin
healthy subjects

Additional relevant MeSH terms:
Esophagitis
Esophagitis, Peptic
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Gastroenteritis
Peptic Ulcer

ClinicalTrials.gov processed this record on August 28, 2014