Reflux OesophagitisPhase 1NCT01599858
Effect of Repeated Doses of YF476, Omeprazole and Placebo on Stomach Acidity in Healthy Volunteers
A Phase 1 study testing YF476 and Omeprazole in people with Reflux Oesophagitis, run by Trio Medicines Ltd. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Reflux Oesophagitis
- What is being tested?
- YF476 and Omeprazole
- Type of treatment
- Pill or oral medicine
- How many people
- 49 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Aug 1996to Oct 1996
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 9Show fewer
- 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.
Who cannot join
- 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.
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
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, 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.
- Conditions
- Reflux Oesophagitis
- Being tested
- YF476, Omeprazole
- Keywords
- YF476, gastrin receptor antagonist, gastric pH, healthy subjects, omeprazole
- Medical subject headings
- Esophagitis, Peptic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YF476Drug
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.
OmeprazoleDrug
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.
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Assessment of safety and tolerability
Physical examination, ECG and safety tests of blood/urine at screening, after the last dose and at follow up.
Measured: 6 weeks
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.
Measured: 6 weeks
Number of adverse events
Adverse events throughout the study
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2012 (estimated)
- Study startAug 1996
- Primary completionOct 1996
- Study completionOct 1996
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Reflux OesophagitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 49 participants (actual)
Sponsor and investigators
- Lead sponsor
- Trio Medicines Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Ferring Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- Malcolm Boyce, Study director, Trio Medicines Limited
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01599858
- Sponsor's protocol ID
- 96-018
- Status last verified
- May 2012
- First submitted
- 10 May 2012
- Last updated
- 16 May 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01599858
- Acronym / sponsor ID
- 96-018
- Conditions
- Reflux Oesophagitis
- Keywords
- YF476, gastrin receptor antagonist, gastric pH, healthy subjects, omeprazole
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 49 participants (actual)
- Lead sponsor
- Trio Medicines Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Ferring Pharmaceuticals
- Study start
- Aug 1996
- Primary completion
- Oct 1996 (actual)
- Study completion
- Oct 1996 (actual)
- First posted
- 16 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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:
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| YF476There 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. | Drug | – |
| OmeprazoleThere 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. | Drug | – |
Primary outcome
Pharmacodynamic measurements: continuous 24h ambulatory gastric pH and 24 h plasma gastrin
Time frame: 6 weeks
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
Time frame: 6 weeks
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
Time frame: 6 weeks
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
Time frame: 6 weeks
Adverse events throughout the study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2012.
Related trials for Reflux Oesophagitis
Recruiting
SPADE Clinical Trial.
Early Gastric Cancer, Adenocarcinoma of the Stomach
Not yet recruitingPhase 4
PPI Dosing Per CYP2C19 Genotype
Gastroesophageal Reflux Disease With Esophagitis
Active, not recruitingPhase 3
Domperidone in Treating Patients With Gastrointestinal Disorders
Digestive System Disorder, Dyspepsia
RecruitingObservational study
Preoperative Predictors of Symptom Improvement After Laparoscopic Fundoplication
Gastroesophageal Reflux Disease, Hiatal Hernia
RecruitingObservational study
A Study of the Safety of Vonoprazan Exposure in Pregnant Women and Their Offspring
Erosive Esophagitis, Heartburn
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Malcolm Boyce study director
Trio Medicines Limited
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing YF476 and Omeprazole in people with Reflux Oesophagitis, run by Trio Medicines Ltd. at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pharmacodynamic measurements: continuous 24h ambulatory gastric pH and 24 h plasma gastrin (time frame: 6 weeks). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2012.