Back to resultsEffect of Repeated Doses of YF476, Omeprazole and Placebo on Stomach Acidity in Healthy Volunteers
Primary Purpose
Reflux Oesophagitis
Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
YF476
Omeprazole
Sponsored by
About this trial
This is an interventional basic science trial for Reflux Oesophagitis focused on measuring YF476, gastrin receptor antagonist, gastric pH, healthy subjects, omeprazole
Eligibility Criteria
Inclusion Criteria:
- Male or female 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:
- 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.
Sites / Locations
- Hammersmith Medicines Research
Outcomes
Primary Outcome Measures
Pharmacodynamic measurements: continuous 24h ambulatory gastric pH and 24 h plasma gastrin
Recording started 0.5 h before the morning dose on Study Day 7 for measurement of gastric pH; meals taken at 4, 9, 13 & 22 h after the morning dose. Frequent blood samples for measurement of plasma gastrin.
Assessment of safety and tolerability
Physical examination, ECG and safety tests of blood/urine at screening, after the last dose and at follow up.
Pharmacokinetic analysis of plasma YF476 concentrations
Blood samples (8 mL) for assay of YF476 taken before each morning dose on Study Days 1-6 and at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 12.25, 12.5, 12.75, 13, 14.5, 15, 16, 17, 18, 20, 22 and 24h on Study Day 7 (where 0h is the time of the morning dose and 12h is the time of the evening dose)for calculation of Cmax, Tmax, AUC 0-24 h, T1/2.
Number of adverse events
Adverse events throughout the study
Secondary Outcome Measures
Full Information
NCT ID
NCT01599858
First Posted
May 10, 2012
Last Updated
May 14, 2012
Sponsor
Trio Medicines Ltd.
Collaborators
Ferring Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01599858
Brief Title
Effect of Repeated Doses of YF476, Omeprazole and Placebo on Stomach Acidity in Healthy Volunteers
Official Title
YF476: Effects of Repeated Dosing at 2 Dose Levels on 24-hour Ambulatory Gastric pH Compared With Placebo and Omeprazole in Healthy Volunteers
Study Type
Interventional
2. Study Status
Record Verification Date
May 2012
Overall Recruitment Status
Completed
Study Start Date
August 1996 (undefined)
Primary Completion Date
October 1996 (Actual)
Study Completion Date
October 1996 (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 objectives of this study were:
To compare repeated doses of YF476 at 2 dose levels, placebo and omeprazole with respect to their effect on basal- and food- stimulated gastric pH in healthy volunteers.
To compare repeated doses of YF476 at 2 dose levels, placebo and omeprazole with respect to their effect on basal and meal stimulated pH.
To assess the safety, tolerability and pharmacokinetics of repeated doses of YF476 in healthy volunteers.
Detailed Description
YF476 is clearly a potent and selective gastrin/CCK-B antagonist and should inhibit basal and meal-stimulated gastric acid secretion, enhance gastric emptying of a liquid meal and increase lower oesphageal sphincter pressure in man. Therefore YF476 might benefit patients with reflux oesophagitis.
YF476 has been well tolerated in healthy volunteers at single doses up to 100mg and remarkably well tolerated at repeat doses in animals up to 350 times the maximum dose planned for the proposed study. A range of doses of YF476 (25 and 100mg twice daily) will be administered to steady state. 24-hour ambulatory gastric pH will be monitored via an intragastric pH electrode to assess the effect of YF476 on basal and meal stimulated gastric pH. 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.
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, healthy subjects, omeprazole
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 as follows: YF476 25mg twice daily, YF476 100mg twice daily, placebo and omeprazole 20mg once daily. Each treatment was taken by mouth for 7 days. Each subject took 1 of the 4 treatments.
Intervention Type
Drug
Intervention Name(s)
Omeprazole
Intervention Description
There were 4 treatments as follows: YF476 25mg twice daily, YF476 100mg twice daily, placebo and omeprazole 20mg once daily. Each treatment was taken by mouth for 7 days. Each subject took 1 of the 4 treatments.
Primary Outcome Measure Information:
Title
Pharmacodynamic measurements: continuous 24h ambulatory gastric pH and 24 h plasma gastrin
Description
Recording started 0.5 h before the morning dose on Study Day 7 for measurement of gastric pH; meals taken at 4, 9, 13 & 22 h after the morning dose. Frequent blood samples for measurement of plasma gastrin.
Time Frame
6 weeks
Title
Assessment of safety and tolerability
Description
Physical examination, ECG and safety tests of blood/urine at screening, after the last dose and at follow up.
Time Frame
6 weeks
Title
Pharmacokinetic analysis of plasma YF476 concentrations
Description
Blood samples (8 mL) for assay of YF476 taken before each morning dose on Study Days 1-6 and at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 12.25, 12.5, 12.75, 13, 14.5, 15, 16, 17, 18, 20, 22 and 24h on Study Day 7 (where 0h is the time of the morning dose and 12h is the time of the evening dose)for calculation of Cmax, Tmax, AUC 0-24 h, T1/2.
Time Frame
6 weeks
Title
Number of adverse events
Description
Adverse events throughout the study
Time Frame
6 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Male or female 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:
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.
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
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Effect of Repeated Doses of YF476, Omeprazole and Placebo on Stomach Acidity in Healthy Volunteers
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