Clopidogrel Pharmacogenetics (PGX) Bench to Bedside

NCT01341600 | Completed Results DMC

• 6 other identifiers: HP-00044487U01GM074518U01HL105198128475ZICSC006536ZICSC006537
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolism of Clopidogrel

Keywords

Clopidogrel; Pharmacogenetics; Platelets; Healthy Subjects

Outcome Measures

Primary Outcomes (2)

• Change in Platelet Aggregation Following Therapy With Clopidogrel

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

  Day 1, 4 hours post clopidogrel dose

• Change in Platelet Aggregation Following Therapy With Clopidogrel

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

  4 hours post Day 8 dose

Secondary Outcomes (2)

• Change in Platelet Aggregation Following Therapy With Clopidogrel and Omeprazole

  Baseline, Day 8

• Level of Active Clopidogrel Metabolite

  Baseline, 0.25, 0.5, 1, 2, and 4 hours

Study Arms (6)

Clopidogrel in poor metabolizers

EXPERIMENTAL

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

Clopidogrel in intermediate metabolizers

EXPERIMENTAL

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

Clopidogrel in extensive metabolizers

EXPERIMENTAL

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

Omeprazole/Clopidogrel in PM

EXPERIMENTAL

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

Omeprazole/Clopidogrel in IM

EXPERIMENTAL

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

Omeprazole/Clopidogrel in EM

EXPERIMENTAL

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

Interventions

Clopidogrel DRUG

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.

Also known as: Plavix

Clopidogrel in extensive metabolizers; Clopidogrel in intermediate metabolizers; Clopidogrel in poor metabolizers

Omeprazole/Clopidogrel DRUG

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.

Also known as: Prilosec, Plavix

Omeprazole/Clopidogrel in EM; Omeprazole/Clopidogrel in IM; Omeprazole/Clopidogrel in PM

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Amish men or women between 20 and 70 years of age who participated in PAPI

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (1)

Amish Research Clinic

Lancaster, Pennsylvania, 17601, United States

Location

Related Publications (3)

• Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, Pollin TI, Post W, Parsa A, Mitchell BD, Faraday N, Herzog W, Gurbel PA. Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009 Aug 26;302(8):849-57. doi: 10.1001/jama.2009.1232.

  PMID: 19706858 BACKGROUND

• Jiang XL, Samant S, Lewis JP, Horenstein RB, Shuldiner AR, Yerges-Armstrong LM, Peletier LA, Lesko LJ, Schmidt S. Development of a physiology-directed population pharmacokinetic and pharmacodynamic model for characterizing the impact of genetic and demographic factors on clopidogrel response in healthy adults. Eur J Pharm Sci. 2016 Jan 20;82:64-78. doi: 10.1016/j.ejps.2015.10.024. Epub 2015 Oct 30.

  PMID: 26524713 BACKGROUND

• Horenstein RB, Madabushi R, Zineh I, Yerges-Armstrong LM, Peer CJ, Schuck RN, Figg WD, Shuldiner AR, Pacanowski MA. Effectiveness of clopidogrel dose escalation to normalize active metabolite exposure and antiplatelet effects in CYP2C19 poor metabolizers. J Clin Pharmacol. 2014 Aug;54(8):865-73. doi: 10.1002/jcph.293. Epub 2014 Apr 7.

  PMID: 24710841 BACKGROUND

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

Results Point of Contact

• Title: Richard Horenstein M.D., Associate Professor of Medicine
• Organization: University of Maryland School of Medicine

rhorenst@medicine.umaryland.edu

410-706-0154

Study Officials

• Richard B Horenstein, M.D.

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 22, 2011
• First Posted: April 25, 2011
• Study Start: July 1, 2010
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: January 30, 2024
• Results First Posted: July 27, 2017

Record last verified: 2024-01

Locations

US (1)