Effects of YF476 and Rabeprazole on Gastric Function

NCT01699113 | Completed Phase 1

• 1 other identifier: 05-021
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypergastrinaemia

Keywords

YF476; gastrin receptor antagonist; gastric pH; gastrin; rabeprazole; proton-pump inhibitor; gastric function; healthy subjects

Outcome Measures

Primary Outcomes (7)

• Measurement of pentagastrin-stimulated gastric volume

• Measurement of pentagastrin-stimulated H+ content (titratable acidity)

• Measurement of pentagastrin-stimulated pH

• Measurement of pentagastrin-stimulated bicarbonate

• Histology of ECL cells

  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

  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

  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 Outcomes (8)

• Measurement of 24-h intragastric pH

• Measurement of 24-h serum gastrin

• Measurement of 24-h plasma SST and CgA

• Measurement of dyspepsia symptoms; antacid usage

• Measurement of pharmacokinetics of YF476 in blood and urine

Interventions

YF476 DRUG

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.

Rabeprazole DRUG

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.

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Trio Medicines Ltd.: lead

Study Sites (1)

Hammersmith Medicines Research

London, United Kingdom

Location

MeSH Terms

Interventions

YF 476; Rabeprazole

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: September 26, 2012
• First Posted: October 3, 2012
• Study Start: August 1, 2006
• Primary Completion: June 1, 2007
• Study Completion: June 1, 2007
• Last Updated: October 3, 2012

Record last verified: 2012-09

Locations

GB (1)