HealthyPhase 1CLARANCT00989300
Influence of Rabeprazole on the Magnitude of the Antiplatelet Action of Clopidogrel
A Phase 1 study testing Treatment A - rabeprazole and Treatment B - omeprazole in people with Healthy, run by Janssen Cilag S.A.S..
Trial summary
The purpose of this study is to assess, whether the administration of a proton pump inhibitor, Rabeprazole, has a negative effect on the activity of a concomitantly administered blood thinner drug. Proton pump inhibitors (PPI's) are prescribed for patients with gastric problems to reduce the gastric acid secretion. Read more about this study
- Who is it for?
- Ages 18 to 50 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Treatment A - rabeprazole and Treatment B - omeprazole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- No sites listed yet
- Study dates
- Nov 2009to Mar 2010
- 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 50 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy Volunteer in good health as determined by a medical history, physical examination including vital signs, and clinical laboratory test results
- Body Mass Index between 18 and 30 kg/m2 (inclusive) and body weight not less than 50 kg
- Non smoker or smokes <5 cigarettes /day, at least 6 months before first study drug
- ECG, blood pressure in normal range (blood pressure measured after the subject is sitting for 5 minutes, between 90 and 140 mm Hg systolic (inclusive) and no higher than 90 mmHg diastolic)
Who cannot join
- Personal or family history of coagulation or bleeding disorders
- Use of known inhibitors or inducers of CYP2C19 and CYP3A, including grape fruit juice intake
- Use of any prescription or non prescription medication (including vitamins and herbal supplements), except for paracetamol (acetaminophen) within 14 days prior to screening
- Known hypersensitivity to clopidogrel, rabeprazole, its excipients, omeprazole or substituted benzimidazoles
- Current clinically significant medical illness or history of clinically significant medical illness
- History of, or reason to believe a volunteer has a history of drug or alcohol abuse within the past 5 years
About this study
Official title: Influence of Rabeprazole on the Magnitude of the Antiplatelet Action of Clopidogrel. A Prospective, placebo-and Active Treatment-controlled, Open Label, Randomized 3-way Cross Over Study in Healthy Subjects
The purpose of this study is to assess, whether the administration of a proton pump inhibitor, Rabeprazole, has a negative effect on the activity of a concomitantly administered blood thinner drug. Proton pump inhibitors (PPI's) are prescribed for patients with gastric problems to reduce the gastric acid secretion. The blood thinner drug, Clopidogrel, administered in this trial is approved for the treatment of mild heart attacks; it works by preventing blood platelets from sticking together to form clots that would restrict blood flow. Previous trials have shown that the proton pump inhibitor omeprazole interacts with the blood thinning drug clopidogrel to reduce the active form of clopidogrel, thereby preventing the drug's blood thinning effect. In this trial, the effect of two different proton pump inhibitors, namely rabeprazole and omeprazole on the activity of the blood thinner drug clopidogrel will be assessed and compared to the effect of placebo on the activity of the blood thinner drug clopidogrel. This will be done in three sequential periods and each of the patients enrolled into this trial will be asked to participate in three different periods, during which clopidogrel with either rabeprazol, or omeprazol, or placebo will be administered daily.
Read the detailed description
In this open-label trial (investigators and patients know, what medication is administered), participants will in the course of three different periods, receive three different combinations of study drugs, namely either clopidogrel combined with rabeprazole, or clopidogrel combined with omeprazole or clopidogrel combined with placebo. Each of these treatment periods will last 7 days and will be interrupted by 2 to 3 weeks without any medication. The goal is to recruit a total of 36 healthy volunteers for all three periods. Clopidogrel is a blood thinner drug that acts on the platelet cell membrane. By this mechanism, clopidogrel inhibits the platelets aggregation. Clopidogrel is a prodrug, meaning that it is orally administrated as an inactive drug and must be activated through several biochemical steps to acquire its antiplatelet properties. This process takes place in the liver and implies a complex enzymatic system. A part of this enzymatic system, called cytochrome 2C19 (CYP2C19) has an important role in the metabolism of the clopidogrel and of other drugs. One of the drugs, which is also metabolized through this system is the proton pump inhibitor (PPI) omeprazole. If omeprazole is given concomitantly with clopidogrel, the metabolism of clopidogrel is inhibited and as a consequence, the therapeutic activity of clopidogrel is reduced. The aim of this study is to investigate whether the proton pump inhibitor rabeprazole, whose metabolism is much less dependent on CYP2C19, interferes less with clopidogrel bioactivation and could thus be proposed as an alternative to other PPIs to patients taking clopidogrel. To confirm that rabeprazole has no clinically relevant effect on the metabolism of clopidogrel, one session is performed with placebo tablets in combination with clopidogrel. Each patient will receive 2 types of study drug during 3 separate periods; either one tablet clopidogrel (75 mg) combined with rabeprazole, or clopidogrel (75 mg) combined with omeprazole or clopidogrel (75 mg) combined with placebo. Each of these treatment periods will last 7 days and will be interrupted by 2 to 3 weeks without any medication.
- Conditions
- Healthy
- Being tested
- Treatment A - rabeprazole, Treatment B - omeprazole, Treatment C - placebo
- Keywords
- Drug-Drug interaction, Clopidogrel, Rabeprazol, Omeprazol, Pharmacodynamic Study
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment A - rabeprazoleDrug
20 mg rabeprazole sodium once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing
Treatment B - omeprazoleDrug
20 mg omeprazole once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing
Treatment C - placeboOther
placebo once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Experimental | patients received clopidogrel 75 mg with rabeprazole 20 mg, omeprazole 20 mg, or placebo in a crossover manner Receives: Drug: Treatment A - rabeprazole; Drug: Treatment B - omeprazole |
| Placebo group | Placebo comparator | Not described Receives: Other: Treatment C - placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The effect of rabeprazole and placebo on inhibition of platelet function after 7 daily standard 75 mg doses of clopidogrel in healthy male volunteers.
Measured: Day 7 of period 1, 2 or 3
Secondary outcomes (3)
The difference in inhibiting the activity of clopidogrel after the administration of rabeprazole compared to placebo
Measured: Measurement at day 7 of period 1, 2 or 3
The difference in inhibiting the activity of clopidogrel after the administration of omeprazole compared to placebo
Measured: measurement at day 7 of period 1, 2, or 3
The difference in inhibiting the activity of clopidogrel after the administration of rabeprazole compared to omeprazole.
Measured: measurement at day 7 of period 1, 2, or 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2009 (estimated)
- Study startNov 2009
- Primary completionMar 2010
- Study completionMar 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Janssen Cilag S.A.S.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Janssen-Cilag S.A.S. Clinical Trial, Study director, Janssen Cilag S.A.S.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00989300
- Sponsor's protocol ID
- CR016333
- Other IDs
- RABGRD1008, 2009-014756-29, 2009
- Acronym
- CLARA
- Status last verified
- Sep 2012
- First submitted
- 2 Oct 2009
- Last updated
- 21 Sep 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Influence of Rabeprazole on the Magnitude of the Antiplatelet Action of Clopidogrel. A Prospective, placebo-and Active Treatment-controlled, Open Label, Randomized 3-way Cross Over Study in Healthy Subjects
- ClinicalTrials.gov ID
- NCT00989300
- Acronym / sponsor ID
- CLARA / CR016333
- Conditions
- Healthy
- Keywords
- Drug-Drug interaction, Clopidogrel, Rabeprazol, Omeprazol, Pharmacodynamic Study
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Janssen Cilag S.A.S.Industry (pharma, biotech, devices)
- Study start
- Nov 2009
- Primary completion
- Mar 2010 (actual)
- Study completion
- Mar 2010 (actual)
- First posted
- 5 Oct 2009 (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 purpose of this study is to assess, whether the administration of a proton pump inhibitor, Rabeprazole, has a negative effect on the activity of a concomitantly administered blood thinner drug. Proton pump inhibitors (PPI's) are prescribed for patients with gastric problems to reduce the gastric acid secretion. The blood thinner drug, Clopidogrel, administered in this trial is approved for the treatment of mild heart attacks; it works by preventing blood platelets from sticking together to form clots that would restrict blood flow. Previous trials have shown that the proton pump inhibitor omeprazole interacts with the blood thinning drug clopidogrel to reduce the active form of clopidogrel, thereby preventing the drug's blood thinning effect. In this trial, the effect of two different proton pump inhibitors, namely rabeprazole and omeprazole on the activity of the blood thinner drug clopidogrel will be assessed and compared to the effect of placebo on the activity of the blood thinner drug clopidogrel. This will be done in three sequential periods and each of the patients enrolled into this trial will be asked to participate in three different periods, during which clopidogrel with either rabeprazol, or omeprazol, or placebo will be administered daily.
Detailed description
In this open-label trial (investigators and patients know, what medication is administered), participants will in the course of three different periods, receive three different combinations of study drugs, namely either clopidogrel combined with rabeprazole, or clopidogrel combined with omeprazole or clopidogrel combined with placebo. Each of these treatment periods will last 7 days and will be interrupted by 2 to 3 weeks without any medication. The goal is to recruit a total of 36 healthy volunteers for all three periods. Clopidogrel is a blood thinner drug that acts on the platelet cell membrane. By this mechanism, clopidogrel inhibits the platelets aggregation. Clopidogrel is a prodrug, meaning that it is orally administrated as an inactive drug and must be activated through several biochemical steps to acquire its antiplatelet properties. This process takes place in the liver and implies a complex enzymatic system. A part of this enzymatic system, called cytochrome 2C19 (CYP2C19) has an important role in the metabolism of the clopidogrel and of other drugs. One of the drugs, which is also metabolized through this system is the proton pump inhibitor (PPI) omeprazole. If omeprazole is given concomitantly with clopidogrel, the metabolism of clopidogrel is inhibited and as a consequence, the therapeutic activity of clopidogrel is reduced. The aim of this study is to investigate whether the proton pump inhibitor rabeprazole, whose metabolism is much less dependent on CYP2C19, interferes less with clopidogrel bioactivation and could thus be proposed as an alternative to other PPIs to patients taking clopidogrel. To confirm that rabeprazole has no clinically relevant effect on the metabolism of clopidogrel, one session is performed with placebo tablets in combination with clopidogrel. Each patient will receive 2 types of study drug during 3 separate periods; either one tablet clopidogrel (75 mg) combined with rabeprazole, or clopidogrel (75 mg) combined with omeprazole or clopidogrel (75 mg) combined with placebo. Each of these treatment periods will last 7 days and will be interrupted by 2 to 3 weeks without any medication.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Experimental | Drug: Treatment A - rabeprazole, Drug: Treatment B - omeprazolepatients received clopidogrel 75 mg with rabeprazole 20 mg, omeprazole 20 mg, or placebo in a crossover manner |
| Placebo group | Placebo comparator | Other: Treatment C - placebo |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Healthy Volunteer in good health as determined by a medical history, physical examination including vital signs, and clinical laboratory test results
- Body Mass Index between 18 and 30 kg/m2 (inclusive) and body weight not less than 50 kg
- Non smoker or smokes <5 cigarettes /day, at least 6 months before first study drug
- ECG, blood pressure in normal range (blood pressure measured after the subject is sitting for 5 minutes, between 90 and 140 mm Hg systolic (inclusive) and no higher than 90 mmHg diastolic)
Key exclusion criteria (6 listed)
- Personal or family history of coagulation or bleeding disorders
- Use of known inhibitors or inducers of CYP2C19 and CYP3A, including grape fruit juice intake
- Use of any prescription or non prescription medication (including vitamins and herbal supplements), except for paracetamol (acetaminophen) within 14 days prior to screening
- Known hypersensitivity to clopidogrel, rabeprazole, its excipients, omeprazole or substituted benzimidazoles
- Current clinically significant medical illness or history of clinically significant medical 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 |
|---|---|---|
| Treatment A - rabeprazole20 mg rabeprazole sodium once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing | Drug | Treatment group |
| Treatment B - omeprazole20 mg omeprazole once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing | Drug | Treatment group |
| Treatment C - placeboplacebo once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing | Other | Placebo group |
Primary outcome
The effect of rabeprazole and placebo on inhibition of platelet function after 7 daily standard 75 mg doses of clopidogrel in healthy male volunteers.
Time frame: Day 7 of period 1, 2 or 3
3 secondary outcomes
The difference in inhibiting the activity of clopidogrel after the administration of rabeprazole compared to placebo
Time frame: Measurement at day 7 of period 1, 2 or 3
The difference in inhibiting the activity of clopidogrel after the administration of omeprazole compared to placebo
Time frame: measurement at day 7 of period 1, 2, or 3
The difference in inhibiting the activity of clopidogrel after the administration of rabeprazole compared to omeprazole.
Time frame: measurement at day 7 of period 1, 2, or 3
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 21 Sep 2012.
- Influence of rabeprazole on the magnitude of the antiplatelet action of clopidogrel. A prospective, placebo and active treatment-controlled, open-label, randomized 3-way cross over study in healthy subjectsLink provided by the sponsor.
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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.
Janssen-Cilag S.A.S. Clinical Trial study director
Janssen Cilag S.A.S.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Treatment A - rabeprazole and Treatment B - omeprazole in people with Healthy, run by Janssen Cilag S.A.S..
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 4 inclusion and 6 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 21 Sep 2012. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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?
The effect of rabeprazole and placebo on inhibition of platelet function after 7 daily standard 75 mg doses of clopidogrel in healthy male volunteers. (time frame: Day 7 of period 1, 2 or 3). 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 21 Sep 2012.