Safety, Tolerability and Pharmacokinetics of Single Rising Doses of YF476, a Gastrin Antagonist, in Healthy Men

NCT01538784 | Completed Phase 1

• 1 other identifier: 96-001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The objectives of the study were:

• To assess the safety, tolerability and pharmacokinetics of YF476 in healthy volunteers.
• To select a dose or doses of YF476 for detailed pharmacodynamic studies in healthy volunteers.

Conditions

Reflux Oesophagitis

Keywords

YF476; gastrin receptor antagonist; gastric pH; healthy subjects

Outcome Measures

Primary Outcomes (3)

• Clinically relevant changes from baseline in safety assessments

  Physical examination, ECG and safety tests of blood and urine at screening and at 24 hours and 7 days after dosing. ECG, blood pressure and heart rate during study period.

  6 weeks

• Numbers of adverse events

  Adverse events during study period and at follow-up.

  6 weeks

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

  Blood samples (10 mL) for assay of YF476 at 0, 0.25, 0.5, 0.75, 1.0, 1.5, 2, 3, 4, 5, 6, 8, 10, 12 and 24 hours after dosing. Urine collection: 0-6, 6-12 and 12-24 hours after dosing.

  6 weeks

Interventions

YF476 DRUG

Two groups of six subjects received single rising oral doses of YF476 capsules or matching placebo. Each subject received 2 doses of YF476 and 1 dose of placebo. 4 subjects received active and 2 placebo at each dose level, as follows: Group A YF476 0.5, 25 and 100mg by mouth Group B YF476 5.0, 50 and 100mg by mouth Groups A \& B were dosed alternately, at weekly intervals

Eligibility Criteria

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

You may qualify if:

• Male 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:

• 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

Condition Hierarchy (Ancestors)

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

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: May 1, 1996
• Primary Completion: June 1, 1996
• Study Completion: June 1, 1996
• Last Updated: February 24, 2012

Record last verified: 2012-02

Locations

GB (1)