Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Effects of YF476 and Rabeprazole on Gastric Function

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Trio Medicines Ltd.
ClinicalTrials.gov Identifier:
NCT01699113
First received: September 26, 2012
Last updated: October 2, 2012
Last verified: September 2012
  Purpose

The primary objectives are to find out in healthy subjects if:

  • YF476 prevents the ECL-cell hyperplasia induced by repeated doses of rabeprazole - a proton pump inhibitor;
  • YF476 also prevents rebound hyperacidity after stopping rabeprazole; and
  • YF476 by itself causes neither ECL-cell hyperplasia after repeated doses nor rebound hyperacidity after stopping YF476.

The secondary objectives are to:

  • assess the safety and tolerability of YF476, alone and in combination with rabeprazole;
  • compare the effects of YF476, alone and in combination with rabeprazole, on serum gastrin and plasma CgA and SST;
  • assess if there is a pharmacokinetic interaction between YF476 and rabeprazole;
  • assess the pharmacokinetics of repeat doses of YF476 by itself; and
  • study the metabolism of YF476.

Condition Intervention Phase
Hypergastrinaemia
Drug: YF476
Drug: Rabeprazole
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Basic Science
Official Title: Effects of YF476, a Gastrin Antagonist, and Rabeprazole, a Proton Pump Inhibitor, Alone and in Combination, on Gastric Function in Healthy Subjects

Resource links provided by NLM:


Further study details as provided by Trio Medicines Ltd.:

Primary Outcome Measures:
  • Measurement of pentagastrin-stimulated gastric volume [ Designated as safety issue: Yes ]
  • Measurement of pentagastrin-stimulated H+ content (titratable acidity) [ Designated as safety issue: Yes ]
  • Measurement of pentagastrin-stimulated pH [ Designated as safety issue: Yes ]
  • Measurement of pentagastrin-stimulated bicarbonate [ Designated as safety issue: Yes ]
  • Histology of ECL cells [ Designated as safety issue: Yes ]

    4 biopsy specimens were taken from the oxyntic mucosa of the body of the stomach. The specimens were prepared and coded for blinded analysis.

    The biopsy specimens were analysed by histology, immunohistochemistry of HDC and CgA, and electron microscopy.


  • Immunostaining of HDC and CgA [ Designated as safety issue: Yes ]

    4 biopsy specimens were taken from the oxyntic mucosa of the body of the stomach. The specimens were prepared and coded for blinded analysis.

    The biopsy specimens were analysed by histology, immunohistochemistry of HDC and CgA, and electron microscopy.


  • Electron microscopy of gastric mucosal biopsies [ Designated as safety issue: Yes ]

    4 biopsy specimens were taken from the oxyntic mucosa of the body of the stomach. The specimens were prepared and coded for blinded analysis.

    The biopsy specimens were analysed by histology, immunohistochemistry of HDC and CgA, and electron microscopy.



Secondary Outcome Measures:
  • Measurement of 24-h intragastric pH [ Designated as safety issue: Yes ]
  • Measurement of 24-h serum gastrin [ Designated as safety issue: Yes ]
  • Measurement of 24-h plasma SST and CgA [ Designated as safety issue: Yes ]
  • Measurement of dyspepsia symptoms; antacid usage [ Designated as safety issue: Yes ]
  • Measurement of pharmacokinetics of YF476 in blood and urine [ Designated as safety issue: Yes ]
    Blood samples for assay of YF476 and/or rabeprazole: before and frequently up to 24 h after the first dose, and at the end of treatment (Day 40); and before dosing on clinic visits during the treatment period, to assess compliance. 3 additional blood samples (4 mL) on Day 40 for future analysis of metabolites. Urine collection 0-24 h after the first dose and at the end of treatment (Day 40), for future analysis of metabolites.

  • Measurement of pharmacokinetics of rabeprazole in blood and urine [ Designated as safety issue: Yes ]
    Blood samples for assay of YF476 and/or rabeprazole: before and frequently up to 24 h after the first dose, and at the end of treatment (Day 40); and before dosing on clinic visits during the treatment period, to assess compliance. 3 additional blood samples (4 mL) on Day 40 for future analysis of metabolites. Urine collection 0-24 h after the first dose and at the end of treatment (Day 40), for future analysis of metabolites.

  • Measurement of safety assessments [ Designated as safety issue: Yes ]
    Physical examination; vital signs; ECG (especially QTc interval); safety tests of blood and urine

  • Number of adverse events [ Designated as safety issue: Yes ]

Enrollment: 32
Study Start Date: August 2006
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: YF476

    Subjects will be randomised to once daily treatment by mouth for 6 weeks with:

    • YF476 100 mg; or
    • rabeprazole 20 mg; or
    • a combination of YF476 100 mg and rabeprazole 20 mg.
    Drug: Rabeprazole

    Subjects will be randomised to once daily treatment by mouth for 6 weeks with:

    • YF476 100 mg; or
    • rabeprazole 20 mg; or
    • a combination of YF476 100 mg and rabeprazole 20 mg.
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Men or women, deemed healthy on the basis of a clinical history, physical examination, ECG and safety tests of blood and urine;
  • able to give fully-informed, written consent.

Exclusion Criteria:

  • Women who are pregnant, lactating or using a steroid contraceptive.
  • Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the pre-trial screening assessment that could interfere with the objectives of the trial or the safety of the subject.
  • Presence of acute or chronic illness or history of chronic illness sufficient to invalidate the subject's participation in the trial 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.
  • Evidence of high serum gastrin at screening or achlorhydria at baseline.
  • Presence or history of severe adverse reaction to any drug.
  • Use of a prescription medicine or antacids during the 28 days before the trial or use of an over-the-counter medication, with the exception of paracetamol, during the 7 days before the trial.
  • Participation in a trial of a new drug substance or a prescription medicine within the previous 3 months.
  • 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 supine 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 of the subject not co-operating with requirements of the protocol.
  • Evidence of drug abuse on urine testing.
  • Positive test for hepatitis B, hepatitis C, HIV1 or HIV2.
  • Loss of > 400 mL blood, e.g. blood donation, in the 3 months before the trial.
  • Objection by the General Practitioner (GP) to the subject entering the trial.
  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: NCT01699113

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

No publications provided

Responsible Party: Trio Medicines Ltd.
ClinicalTrials.gov Identifier: NCT01699113     History of Changes
Other Study ID Numbers: 05-021
Study First Received: September 26, 2012
Last Updated: October 2, 2012
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Trio Medicines Ltd.:
YF476
gastrin receptor antagonist
gastric pH
gastrin
rabeprazole
proton-pump inhibitor
gastric function
healthy subjects

Additional relevant MeSH terms:
Proton Pump Inhibitors
Rabeprazole
Anti-Ulcer Agents
Enzyme Inhibitors
Gastrointestinal Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 20, 2014