Back to resultsEffect of 5, 10 or 25 mg of YF476 Daily for 14 Days on Stomach Acidity in Healthy Volunteers
Primary Purpose
Reflux Oesophagitis
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
YF476
Sponsored by
About this trial
This is an interventional basic science trial for Reflux Oesophagitis focused on measuring YF476, gastrin receptor antagonist, gastric pH, gastrin, healthy subjects
Eligibility 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.
Sites / Locations
- Hammersmith Medicines Research
Outcomes
Primary Outcome Measures
Pharmacodynamic parameters: gastric pH and plasma gastrin
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
Physical examination, ECG and safety tests of blood/urine at screening and at follow up.
Numbers of adverse events
Adverse events throughout study.
Secondary Outcome Measures
Full Information
NCT ID
NCT01597674
First Posted
May 10, 2012
Last Updated
May 11, 2012
Sponsor
Trio Medicines Ltd.
Collaborators
Ferring Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01597674
Brief Title
Effect of 5, 10 or 25 mg of YF476 Daily for 14 Days on Stomach Acidity in Healthy Volunteers
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
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
April 1997 (undefined)
Primary Completion Date
June 1997 (Actual)
Study Completion Date
June 1997 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Trio Medicines Ltd.
Collaborators
Ferring Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Reflux Oesophagitis
Keywords
YF476, gastrin receptor antagonist, gastric pH, gastrin, healthy subjects
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
49 (Actual)
8. Arms, Groups, and Interventions
Intervention Type
Drug
Intervention Name(s)
YF476
Intervention Description
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.
Primary Outcome Measure Information:
Title
Pharmacodynamic parameters: gastric pH and plasma gastrin
Description
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.
Time Frame
8 weeks
Title
Clinically relevant changes from baseline in safety assessments
Description
Physical examination, ECG and safety tests of blood/urine at screening and at follow up.
Time Frame
8 weeks
Title
Numbers of adverse events
Description
Adverse events throughout study.
Time Frame
8 weeks
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Malcolm Boyce
Organizational Affiliation
Trio Medicines Limited
Official's Role
Study Director
Facility Information:
Facility Name
Hammersmith Medicines Research
City
London
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Effect of 5, 10 or 25 mg of YF476 Daily for 14 Days on Stomach Acidity in Healthy Volunteers
We'll reach out to this number within 24 hrs