Influence of Rabeprazole on the Magnitude of the Antiplatelet Action of Clopidogrel
Condition: Healthy
Study type: Interventional
Phase: Phase 1

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. 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.
    

Intervention name(s): Treatment A - rabeprazole; Treatment B - omeprazole; Treatment C - placebo
Intervention type(s): Drug; Drug; Other
Intervention description(s): 20 mg rabeprazole sodium once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing; 20 mg omeprazole once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing; placebo once daily for 7 days, in combination with 75 mg clopidogrel once daily for 7 days, oral dosing
Intervention MeSH terms: Omeprazole; Rabeprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Drug-Drug interaction; Clopidogrel; Rabeprazol; Omeprazol; Pharmacodynamic Study