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CompletedNCT01538797Updated Feb 24, 2012

Effect of Single Doses of YF476 on Stomach Acidity Compared With Ranitidine and Placebo in Fasted and Fed States

A Phase 1 interventional study of YF476 and Ranitidine in Reflux Oesophagitis, sponsored by Trio Medicines Ltd.. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2012-02-24.

Sponsored by Trio Medicines Ltd. · Phase 1, Interventional, and Basic science

Phase
Phase 1
Study type
Interventional
Enrollment
22
Allocation
Randomized
Ages
18 Years to 45 Years
Sex
All
01

Study summary

The objectives of the study were:

  • To compare a single dose of YF476 at 3 dose levels, placebo and ranitidine with respect to their effects on basal- and food- stimulated gastric pH in healthy volunteers.
  • To assess whether there is a relationship between the pharmacokinetics of YF476 and gastric pH in healthy volunteers.
  • To assess the safety and tolerability of single doses of YF476 in healthy volunteers.
Read the detailed description

YF476 is clearly a potent and selective gastrin/CCK-B antagonist and should inhibit basal and meal-stimulated gastric acid secretion and enhance gastric emptying of a liquid meal in man. Therefore YF476 might benefit patients with reflux oesophagitis. The compound has been well tolerated in animal toxicity studies at doses in excess of the projected therapeutic dose in patients, and merits studies in healthy volunteers. Extrapolation from data obtained in animals suggests that a single oral dose of about 10mg of YF476 should compare favourably with an oral dose of 150mg of ranitidine in man with respect to effect on basal and food-stimulated gastric acid secretion. Therefore in the proposed study a range of doses of YF476 encompassing that dose will be studied; the exact dose of YF476 will be chosen on the basis of the previous study but the top dose will not exceed 100mg. 24-hour ambulatory gastric pH will be monitored via an intragastric pH electrode (7-10). Although there is variability between subjects with respect to the effects of food and drug treatment on gastric pH, the methodology for measurement of ambulatory gastric pH is robust.

02

Conditions studied

  • Reflux Oesophagitis

Keywords

  • YF476
  • gastrin receptor antagonist
  • gastric pH
  • healthy subjects
  • ranitidine
03

In context

Esophagitis

322 studies on the registry are indexed under Esophagitis; 37 are open to participants now.

This study's enrollment of 22 is below the median of 66 across 215 interventional studies indexed under Esophagitis.

Browse Esophagitis studies →

Lead sponsor

Trio Medicines Ltd. is the lead sponsor of 14 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 45 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

  • Male or female 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.

Exclusion criteria

Exclusion Criteria:

  • Females who are pregnant or lactating, or who are sexually active and are not using a reliable method of contraception.
  • 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 or heart rate outside those values specified under inclusion criterion (f).
  • 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.
05

Study design

Phase
Phase 1
Primary purpose
Basic science
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
22 participants (actual)

Interventions

  • DrugYF476

    There were 5 treatments: 3 dose levels of YF476 (5, 25 and 100 mg), placebo and ranitidine 150 mg. There were at least 7 days between consecutive Treatment Days.

  • DrugRanitidine

    There were 5 treatments: 3 dose levels of YF476 (5, 25 and 100mg), placebo and ranitidine 150mg. There were at least 7 days between consecutive Treatment Days.

06

What researchers measure

Primary outcomes

  1. Clinically relevant changes from baseline in safety assessments

    Physical examination, ECG and safety tests of blood/urine at screening, 24h after dosing on each Treatment Day and at follow up. Blood pressure and heart rate before and at 0.5, 1, 2, 4, 6, 8, 12 and 24h after dosing on each Treatment Day.

    Time frame: 6 weeks

  2. Numbers of adverse events

    Adverse events throughout the study

    Time frame: 6 weeks

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

    Blood samples (8mL) before and at 0.5, 1, 2, 4, 6, 8, 12 and 24h after each dose for assay of YF476.

    Time frame: 6 weeks

  4. Pharmacodynamic parameters: continuous 24 h ambulatory gastric pH

    Recording starts 0.5h before dosing on each Treatment Day; meals taken at 4, 9, 13 \& 22h after dosing.

    Time frame: 6 weeks

07

Study locations

1 site
  • Hammersmith Medicines Research
    London, NW10 7EW, United Kingdom
08

References and documents

Publications

  • 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. PubMed 22607579 ↗
09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 24, 2012, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT01538797
Lead sponsor
Trio Medicines Ltd.
Collaborators
Ferring Pharmaceuticals
Responsible party
Sponsor
First posted
Feb 24, 2012
Start date
Jul 1996
Primary completion
Aug 1996
Completion
Aug 1996
Last update
Feb 24, 2012

Study contacts

Malcolm J Boyce, FRCP FFPM
study director · Trio Medicines Limited

Oversight

Data monitoring committee
No
View the source record on ClinicalTrials.gov ↗

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