PGXB2B: Clopidogrel Pharmacogenetics (PGX) Bench to Bedside

Sponsor
University of Maryland, Baltimore (Other)
Overall Status
Completed
CT.gov ID
NCT01341600
Collaborator
Food and Drug Administration (FDA) (U.S. Fed), National Cancer Institute (NCI) (NIH), National Institute of General Medical Sciences (NIGMS) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH)
18
1
6
10
1.8

Study Details

Study Description

Brief Summary

Clopidogrel (also known as Plavix) is used commonly in patients to prevent heart attacks and conditions caused by blood clots. Although clopidogrel works in many individuals, some people do not respond as well to this drug. The variation in treatment response may be linked to genetics. This study will examine the effects of clopidogrel in a population in which sequencing for certain genes has been performed in order to determine the role that genes play in the response to various clopidogrel maintenance doses.

Condition or Disease Intervention/Treatment Phase
N/A

Detailed Description

Clopidogrel is a prodrug with high inter-individual response variability. Clopidogrel is converted to an active drug in part through an enzyme encoded by the gene named CYP2C19. Individuals with genetically-impaired CYP2C19 metabolism have lower capacity to convert the prodrug to its active form. Consequently, these individuals have lower blood levels of the activated form of clopidogrel, diminished antiplatelet responses, and higher rates of cardiovascular events and stent thrombosis. Increasing doses of clopidogrel in such patients represents a possible approach to managing the gene-drug interaction.

The purpose of this study is to evaluate whether increasing the dose of clopidogrel increases antiplatelet responses and active metabolite exposure in individuals with genetically reduced CYP2C19 metabolism relative to those with normal CYP2C19 metabolism.

The primary objective is to assess changes in clopidogrel response and exposure at three clopidogrel dose levels and with coadministration of omeprazole.

Study Design

Study Type:
Interventional
Actual Enrollment :
18 participants
Allocation:
Non-Randomized
Intervention Model:
Crossover Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Clopidogrel Pharmacogenetics Bench to Bedside - A Practical Application
Study Start Date :
Jul 1, 2010
Actual Primary Completion Date :
May 1, 2011
Actual Study Completion Date :
May 1, 2011

Arms and Interventions

Arm Intervention/Treatment
Experimental: Clopidogrel in poor metabolizers

Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers (PM) to clopidogrel 75 mg from participants who previously received 75 mg clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Over a 6 week period participants will be given: 75 mg of clopidogrel for 8 days, at least 1 week washout, 150 mg of clopidogrel for eight days, at least 1 week washout, 300 mg of clopidogrel for eight days.

Drug: Clopidogrel
Over a 6 week period participants will be given: 75 mg of clopidogrel for 8 days, at least 1 week washout, 150 mg of clopidogrel for eight days, at least 1 week washout, 300 mg of clopidogrel for eight days.
Other Names:
  • Plavix
  • Experimental: Clopidogrel in intermediate metabolizers

    Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers (IM) to clopidogrel 75 mg from participants who previously received 75 mg clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Over a 6 week period participants will be given: 75 mg of clopidogrel for 8 days, at least 1 week washout, 150 mg of clopidogrel for eight days, at least 1 week washout, 300 mg of clopidogrel for eight days.

    Drug: Clopidogrel
    Over a 6 week period participants will be given: 75 mg of clopidogrel for 8 days, at least 1 week washout, 150 mg of clopidogrel for eight days, at least 1 week washout, 300 mg of clopidogrel for eight days.
    Other Names:
  • Plavix
  • Experimental: Clopidogrel in extensive metabolizers

    Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers (EM) to clopidogrel 75 mg from participants who previously received 75 mg clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Over a 6 week period participants will be given: 75 mg of clopidogrel for 8 days, at least 1 week washout, 150 mg of clopidogrel for eight days, at least 1 week washout, 300 mg of clopidogrel for eight days.

    Drug: Clopidogrel
    Over a 6 week period participants will be given: 75 mg of clopidogrel for 8 days, at least 1 week washout, 150 mg of clopidogrel for eight days, at least 1 week washout, 300 mg of clopidogrel for eight days.
    Other Names:
  • Plavix
  • Experimental: Omeprazole/Clopidogrel in PM

    PM participants who have completed Arm 1 will have the option to participate. After a washout of at least one week, these participants will given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.

    Drug: Omeprazole/Clopidogrel
    After a washout of at least 1 week, participants will have the option to participate in a final intervention in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    Other Names:
  • Prilosec
  • Plavix
  • Experimental: Omeprazole/Clopidogrel in IM

    IM participants who have completed Arm 2 will have the option to participate. After a washout of at least one week, these participants will given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.

    Drug: Omeprazole/Clopidogrel
    After a washout of at least 1 week, participants will have the option to participate in a final intervention in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    Other Names:
  • Prilosec
  • Plavix
  • Experimental: Omeprazole/Clopidogrel in EM

    EM participants who have completed Arm 3 will have the option to participate. After a washout of at least one week, these participants will given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.

    Drug: Omeprazole/Clopidogrel
    After a washout of at least 1 week, participants will have the option to participate in a final intervention in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    Other Names:
  • Prilosec
  • Plavix
  • Outcome Measures

    Primary Outcome Measures

    1. Change in Platelet Aggregation Following Therapy With Clopidogrel [Day 1, 4 hours post clopidogrel dose]

      Adenosine diphosphate (ADP) mediated platelet aggregation measured 4 hours post-dose of clopidogrel on Day 1.

    2. Change in Platelet Aggregation Following Therapy With Clopidogrel [4 hours post Day 8 dose]

      ADP mediated platelet aggregation measured 4 hours post Day 8 clopidogrel dose

    Secondary Outcome Measures

    1. Change in Platelet Aggregation Following Therapy With Clopidogrel and Omeprazole [Baseline, Day 8]

      The change in maximum platelet aggregation in response to ADP 4-hours post dose on day 8 of therapy with clopidogrel and omeprazole will be compared to the baseline measure of platelet aggregation at day 1 prior to drug therapy

    2. Level of Active Clopidogrel Metabolite [Baseline, 0.25, 0.5, 1, 2, and 4 hours]

      The level of the active clopidogrel metabolite will be measured at at 0.25, 0.5, 1, 2, and 4 hours after the Day One dose is administered for pharmacokinetic analysis. The analysis will measure the Area Under the Curve.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years to 70 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria:
    • Amish men or women between 20 and 70 years of age who participated in PAPI
    Exclusion Criteria:
    • Severe hypertension (bp > 160/95 mm Hg)

    • Co-existing malignancy

    • Aspartate Aminotransferase (AST) or Alanine Aminotransferase (ALT) > 2 times normal

    • Creatinine >2.0

    • Hct < 32 or Hct > 50

    • Thyroid Stimulating Hormone (TSH) < 0.40 or >5.50

    • History of bleeding disorder or gastrointestinal bleeding

    • History of unstable angina, myocardial infarction (MI), angioplasty, coronary artery bypass surgery

    • History of atrial fibrillation, stroke or transient ischemic attacks or deep vein thrombosis

    • Type 2 diabetes

    • Thrombocytosis (platelet count > 500,000) or thrombocytopenia (platelet count < 150,000)

    • Surgery within six months

    • Clopidogrel allergy

    • Pregnant women

    • Currently breast feeding

    • Omeprazole allergy

    • Prospective participants taking medications that would affect the outcome(s) to be measured and who cannot willingly and safely, in the opinion of the treating physician and study physician, discontinue these medications for 1 week prior to protocol initiation, or who are taking vitamins and/or other supplements and who are unwilling to discontinue their use for at least 1 week prior to study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Amish Research Clinic Lancaster Pennsylvania United States 17601

    Sponsors and Collaborators

    • University of Maryland, Baltimore
    • Food and Drug Administration (FDA)
    • National Cancer Institute (NCI)
    • National Institute of General Medical Sciences (NIGMS)
    • National Heart, Lung, and Blood Institute (NHLBI)

    Investigators

    • Principal Investigator: Richard B Horenstein, M.D., University of Maryland School of Medicine

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Alan Shuldiner, Professor of Medicine, University of Maryland, Baltimore
    ClinicalTrials.gov Identifier:
    NCT01341600
    Other Study ID Numbers:
    • HP-00044487
    • U01GM074518
    • U01HL105198
    • 128475
    • ZICSC006536
    • ZICSC006537
    First Posted:
    Apr 25, 2011
    Last Update Posted:
    Feb 23, 2022
    Last Verified:
    Feb 1, 2022
    Keywords provided by Alan Shuldiner, Professor of Medicine, University of Maryland, Baltimore
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Arm/Group Description Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI (NCT00799396)) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI (NCT00799396)) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI (NCT00799396)) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    Period Title: Clopidogrel 75 mg
    STARTED 6 6 6
    COMPLETED 6 6 6
    NOT COMPLETED 0 0 0
    Period Title: Clopidogrel 75 mg
    STARTED 6 6 6
    COMPLETED 6 6 6
    NOT COMPLETED 0 0 0
    Period Title: Clopidogrel 75 mg
    STARTED 6 6 6
    COMPLETED 6 6 6
    NOT COMPLETED 0 0 0
    Period Title: Clopidogrel 75 mg
    STARTED 5 5 4
    COMPLETED 5 5 4
    NOT COMPLETED 0 0 0

    Baseline Characteristics

    Arm/Group Title Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers Total
    Arm/Group Description Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Total of all reporting groups
    Overall Participants 6 6 6 18
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    6
    100%
    6
    100%
    6
    100%
    18
    100%
    >=65 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Sex: Female, Male (Count of Participants)
    Female
    2
    33.3%
    2
    33.3%
    2
    33.3%
    6
    33.3%
    Male
    4
    66.7%
    4
    66.7%
    4
    66.7%
    12
    66.7%
    Region of Enrollment (participants) [Number]
    United States
    6
    100%
    6
    100%
    6
    100%
    18
    100%

    Outcome Measures

    1. Primary Outcome
    Title Change in Platelet Aggregation Following Therapy With Clopidogrel
    Description Adenosine diphosphate (ADP) mediated platelet aggregation measured 4 hours post-dose of clopidogrel on Day 1.
    Time Frame Day 1, 4 hours post clopidogrel dose

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Arm/Group Description Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    Measure Participants 6 6 6
    Clopidogrel 75mg
    62.9
    (14.7)
    68.1
    (5.0)
    62.5
    (3.4)
    Clopidogrel 150mg
    63.2
    (9.3)
    57.8
    (7.2)
    53.9
    (12.9)
    Clopidogrel 300mg
    53.3
    (15.2)
    47.8
    (13.6)
    38.6
    (10.9)
    2. Secondary Outcome
    Title Change in Platelet Aggregation Following Therapy With Clopidogrel and Omeprazole
    Description The change in maximum platelet aggregation in response to ADP 4-hours post dose on day 8 of therapy with clopidogrel and omeprazole will be compared to the baseline measure of platelet aggregation at day 1 prior to drug therapy
    Time Frame Baseline, Day 8

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Arm/Group Description Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    Measure Participants 5 5 4
    Mean (Standard Deviation) [percentage of aggregation]
    11.6
    (11.9)
    27.9
    (9.3)
    37.5
    (3.2)
    3. Secondary Outcome
    Title Level of Active Clopidogrel Metabolite
    Description The level of the active clopidogrel metabolite will be measured at at 0.25, 0.5, 1, 2, and 4 hours after the Day One dose is administered for pharmacokinetic analysis. The analysis will measure the Area Under the Curve.
    Time Frame Baseline, 0.25, 0.5, 1, 2, and 4 hours

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Arm/Group Description Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    Measure Participants 6 6 6
    Clopidogrel 75mg
    17.4
    (19)
    33.3
    (37)
    32.7
    (25)
    Clopidogrel 150mg
    24.2
    (26)
    43.8
    (35)
    53.6
    (35)
    Clopidogrel 300mg
    36
    (35)
    73.7
    (53)
    80.4
    (24)
    4. Primary Outcome
    Title Change in Platelet Aggregation Following Therapy With Clopidogrel
    Description ADP mediated platelet aggregation measured 4 hours post Day 8 clopidogrel dose
    Time Frame 4 hours post Day 8 dose

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Arm/Group Description Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    Measure Participants 6 6 6
    Clopidogrel 75mg
    55.0
    (14.5)
    37.8
    (8.2)
    31.3
    (7.3)
    Clopidogrel 150mg
    44.2
    (15.0)
    33.2
    (6.0)
    25.1
    (7.1)
    Clopidogrel 300mg
    32.6
    (10.7)
    25.7
    (6.0)
    19.5
    (6.9)

    Adverse Events

    Time Frame Six weeks
    Adverse Event Reporting Description
    Arm/Group Title Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Arm/Group Description Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 poor metabolizers to clopidogrel 75 mg from participants who previously received clopidogrel as part of another NIH sponsored clinical trial entitled, "Pharmacogenetics of Anti-platelet Intervention" (PAPI) Study (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 intermediate metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days. Healthy subjects who have been genotyped for CYP2C19*2 and received clopidogrel as part of a prior study (PAPI) will be recruited. We will select 6 extensive metabolizers to clopidogrel 75 mg in PAPI (NCT 00799396). Clopidogrel, Omeprazole: Over a 6 week period participants will be given: 75mg of clopidogrel for 8 days, at least 1 week washout, 150mg of clopidogrel for eight days, at least 1 week washout, 300mg of clopidogrel for eight days. Participants will have the option to participate in a final week in which they will be given 75 mg of clopidogrel together with 20 mg of omeprazole daily for eight days.
    All Cause Mortality
    Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 0/6 (0%) 0/6 (0%)
    Other (Not Including Serious) Adverse Events
    Poor Metabolizers Intermediate Metabolizers Extensive Metabolizers
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/6 (0%) 1/6 (16.7%) 1/6 (16.7%)
    Infections and infestations
    skin infection 0/6 (0%) 0/6 (0%) 1/6 (16.7%)
    Nervous system disorders
    vasovagal reaction 0/6 (0%) 1/6 (16.7%) 0/6 (0%)
    Skin and subcutaneous tissue disorders
    Rash maculo-papular 0/6 (0%) 0/6 (0%) 1/6 (16.7%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Richard Horenstein M.D., Associate Professor of Medicine
    Organization University of Maryland School of Medicine
    Phone 410-706-0154
    Email rhorenst@medicine.umaryland.edu
    Responsible Party:
    Alan Shuldiner, Professor of Medicine, University of Maryland, Baltimore
    ClinicalTrials.gov Identifier:
    NCT01341600
    Other Study ID Numbers:
    • HP-00044487
    • U01GM074518
    • U01HL105198
    • 128475
    • ZICSC006536
    • ZICSC006537
    First Posted:
    Apr 25, 2011
    Last Update Posted:
    Feb 23, 2022
    Last Verified:
    Feb 1, 2022