Interaction Study of Clopidogrel 600/150 mg Given Alone or Concomitantly With Omeprazole 80 mg in Healthy Subjects

NCT01129414 | Completed Phase 1

• 2 other identifiers: INT112082009-011005-16
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective:

• Assess the effects of clopidogrel (600 mg loading dose followed by 4 days 150 mg/day) on Adenosine diphosphate (ADP)-induced platelet aggregation when given concomitantly with omeprazole 80 mg/day compared to given alone in healthy male and female subjects Secondary Objective:
• Compare the pharmacokinetic profiles of clopidogrel and its active metabolite when clopidogrel is given either alone or concomitantly with omeprazole

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• Maximum platelet aggregation intensity (MAI) induced by Adenosine diphosphate (ADP) 5µM after 5 days treatment

  Day 5 of each period

Secondary Outcomes (4)

• Maximum platelet aggregation intensity (MAI) induced by ADP 20µM after 5 days treatment

  Day 5 of each period

• Platelet Reactivity Index - Vasodilatator-stimulated phosphoprotein test (PRI - VASP) after 5 days treatment

  Day 5 of each period

• Clopidogrel pharmacokinetic parameters (maximum plasma concentration (Cmax) and area under the plasma concentration curve (AUC0-24)) after 5 days treatment

  Up to 24 hours postdose on Day 5 for each period

• Clopidogrel active metabolite pharmacokinetic parameters (Cmax and AUC0-24) after 5 days treatment

  Up to 24 hours postdose on Day 5 for each period

Study Arms (4)

Group clopidogrel - clopidogrel + omeprazole

EXPERIMENTAL

Period 1: * Day 1: clopidogrel 600 mg loading dose * Day 2 to Day 5: clopidogrel 150 mg, once daily Period 2: * Day -5 to Day -1: omeprazole 80 mg, once daily * Day 1: clopidogrel 600 mg loading dose + omeprazole 80 mg concomitantly * Day 2 to Day 5: clopidogrel 150 mg + omeprazole 80 mg concomitantly, once daily Each intake is under fasted conditions

Drug: Clopidogrel; Drug: Omeprazole

Group placebo - placebo + omeprazole

PLACEBO COMPARATOR

Period 1: * Day 1: placebo loading dose * Day 2 to Day 5: placebo, once daily Period 2: * Day -5 to Day -1: omeprazole 80 mg, once daily * Day 1: placebo loading dose + omeprazole 80 mg concomitantly * Day 2 to Day 5: placebo + omeprazole 80 mg concomitantly, once daily Each intake is under fasted conditions

Drug: Placebo; Drug: Omeprazole

Group clopidogrel + omeprazole - clopidogrel

EXPERIMENTAL

Period 1: * Day -5 to Day -1: omeprazole 80 mg, once daily * Day 1: clopidogrel 600 mg loading dose + omeprazole 80 mg concomitantly * Day 2 to Day 5: clopidogrel 150 mg + omeprazole 80 mg concomitantly, once daily Period 2: * Day 1: clopidogrel 600 mg loading dose * Day 2 to Day 5: clopidogrel 150 mg, once daily Each intake is under fasted conditions

Drug: Clopidogrel; Drug: Omeprazole

Group placebo + omeprazole placebo

PLACEBO COMPARATOR

Period 1: * Day -5 to Day -1: omeprazole 80 mg, once daily * Day 1: placebo loading dose + omeprazole 80 mg concomitantly * Day 2 to Day 5: placebo + omeprazole 80 mg concomitantly, once daily Period 2: * Day 1: placebo loading dose * Day 2 to Day 5: placebo, once daily Each intake is under fasted conditions

Drug: Placebo; Drug: Omeprazole

Interventions

Clopidogrel DRUG

Pharmaceutical form: tablet Route of administration: oral

Also known as: SR25990

Group clopidogrel + omeprazole - clopidogrel; Group clopidogrel - clopidogrel + omeprazole

Placebo DRUG

Pharmaceutical form: matching tablet Route of administration: oral

Group placebo + omeprazole placebo; Group placebo - placebo + omeprazole

Omeprazole DRUG

Pharmaceutical form: delayed-release capsule Route of administration: oral

Group clopidogrel + omeprazole - clopidogrel; Group clopidogrel - clopidogrel + omeprazole; Group placebo + omeprazole placebo; Group placebo - placebo + omeprazole

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy subject:
• as determined by medical history, physical examination including vital signs and clinical laboratory tests:
• with a body weight between 50 kg and 95 kg if male, between 40 kg and 85 kg if female, and with a Body Mass Index (BMI) between 18 and 30 kg/m²

You may not qualify if:

• Evidence of inherited disorder of coagulation/hemostasis functions
• Smoking more than 5 cigarettes or equivalent per day
• Abnormal hemostasis screen
• Unability to abstain from intake of any drug affecting hemostasis throughout the whole study duration \>Any contraindication to clopidogrel and/or omeprazole
• The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, 08807, United States

Location

Related Publications (1)

• Angiolillo DJ, Gibson CM, Cheng S, Ollier C, Nicolas O, Bergougnan L, Perrin L, LaCreta FP, Hurbin F, Dubar M. Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther. 2011 Jan;89(1):65-74. doi: 10.1038/clpt.2010.219. Epub 2010 Sep 15.

  PMID: 20844485 RESULT

MeSH Terms

Interventions

Clopidogrel; Omeprazole

Intervention Hierarchy (Ancestors)

Ticlopidine; Thienopyridines; Thiophenes; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; 2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Benzimidazoles

Study Officials

• International Clinical Development Study Director

  Sanofi

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2010
• First Posted: May 24, 2010
• Study Start: June 1, 2009
• Primary Completion: August 1, 2009
• Study Completion: August 1, 2009
• Last Updated: December 15, 2011

Record last verified: 2011-12

Locations

US (1)