PGXB2B: Clopidogrel Pharmacogenetics (PGX) Bench to Bedside
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
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:
|
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:
|
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:
|
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:
|
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:
|
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:
|
Outcome Measures
Primary Outcome Measures
- 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.
- 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
- 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
- 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
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
- HP-00044487
- U01GM074518
- U01HL105198
- 128475
- ZICSC006536
- ZICSC006537
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
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)
|
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)
|
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)
|
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 |
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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 |
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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 |
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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
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 |
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Organization | University of Maryland School of Medicine |
Phone | 410-706-0154 |
rhorenst@medicine.umaryland.edu |
- HP-00044487
- U01GM074518
- U01HL105198
- 128475
- ZICSC006536
- ZICSC006537