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Influence of Rabeprazole on the Magnitude of the Antiplatelet Action of Clopidogrel (CLARA)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen Cilag S.A.S.
ClinicalTrials.gov Identifier:
NCT00989300
First received: October 2, 2009
Last updated: September 19, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Healthy
Drug: Treatment A - rabeprazole
Drug: Treatment B - omeprazole
Other: Treatment C - placebo
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Janssen Cilag S.A.S.:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Enrollment: 39
Study Start Date: November 2009
Study Completion Date: March 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment group
patients received clopidogrel 75 mg with rabeprazole 20 mg, omeprazole 20 mg, or placebo in a crossover manner
Drug: Treatment A - rabeprazole
20 mg rabeprazole sodium once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing
Drug: Treatment B - omeprazole
20 mg omeprazole once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing
Placebo Comparator: Placebo group Other: Treatment C - placebo
placebo once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00989300

Sponsors and Collaborators
Janssen Cilag S.A.S.
Investigators
Study Director: Janssen-Cilag S.A.S. Clinical Trial Janssen Cilag S.A.S.
  More Information

Additional Information:
No publications provided

Responsible Party: Janssen Cilag S.A.S.
ClinicalTrials.gov Identifier: NCT00989300     History of Changes
Other Study ID Numbers: CR016333, RABGRD1008, 2009-014756-29
Study First Received: October 2, 2009
Last Updated: September 19, 2012
Health Authority: France: Ministry of Health
United States: Food and Drug Administration

Keywords provided by Janssen Cilag S.A.S.:
Drug-Drug interaction
Clopidogrel
Rabeprazol
Omeprazol
Pharmacodynamic Study

Additional relevant MeSH terms:
Clopidogrel
Omeprazole
Rabeprazole
Anti-Ulcer Agents
Enzyme Inhibitors
Gastrointestinal Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Proton Pump Inhibitors
Purinergic Agents
Purinergic Antagonists
Purinergic P2 Receptor Antagonists
Purinergic P2Y Receptor Antagonists
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014