Healthy Volunteer Study of Clopidogrel and Rifampicin

NCT00696566 | Completed Phase 1

• 2 other identifiers: STH14468BHF Grant: PG/05/095
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

The principal research question is: Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin? Clopidogrel is an antithrombotic drug in clinical use that reduces the risk of heart attack and coronary stent thrombosis. However some patients respond poorly to clopidogrel, at least partly because they fail to convert it effectively to its active form, and consequently are at higher risk of arterial thrombosis. Preliminary evidence indicates that the antibiotic rifampicin enhances the effectiveness of clopidogrel by increasing its conversion to its active form by the liver. We wish to study further the extent of rifampicin's effect on clopidogrel to see whether this might be useful in clinical practice.

Conditions

Coronary Artery Disease

Keywords

Thrombosis; Platelet aggregation inhibitor; Blood platelets; P2 receptor; Cytochrome P450

Outcome Measures

Primary Outcomes (1)

• Can platelet P2Y12 receptor blockade by the antithrombotic drug clopidogrel be significantly enhanced by coadministration of the antibiotic rifampicin?

  All year

Study Arms (1)

A

EXPERIMENTAL

All subjects will receive Clopidogrel and Rifampicin.

Drug: Clopidogrel and Rifampicin

Interventions

Clopidogrel and Rifampicin DRUG

Clopidogrel: loading dose of 600 mg, then 75 mg o.d. for up to 28 days Rifampicin: 300 mg b.d. for up to 28 days

Also known as: Clopidorel = Plavix, Rifampicin = Rifadin

A

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 male subjects, or female subjects not of childbearing potential (either surgically sterile or post menopausal).
• Age between 18 and 65 years inclusive.
• Non smokers.
• Body mass index (BMI) between 18 and 28 kg/m2 inclusive, with a body weight between 60 - 100 kg.
• Subjects are to be in good health as determined by a medical history, physical examination including vital signs, and clinical laboratory test results including liver function and full blood count.
• Subjects have given their signed informed consent before any trial-related activity.

You may not qualify if:

• In the opinion of the investigator, subjects with, or a history of, cancer, diabetes or clinically significant cardiovascular, respiratory, metabolic, renal, hepatic, gastrointestinal, haematological, dermatological, neurological, psychiatric or other major disorders.
• Subjects with a history of significant multiple drug allergies or with a known allergy to the study drugs or any medicine chemically related to the trial product.
• Subjects who have a clinically significant allergic disease (including hay fever).
• Subjects who have had a clinically significant illness within 4 weeks of dosing.
• Subjects taking regular medication including NSAID's, antibiotics, aspirin or anticoagulant therapy.
• Any clinically significant abnormal laboratory test results at screening.
• Subjects who have a supine blood pressure at screening, after resting for 5 min higher than 150/90 mmHg or lower than 100/50 mmHg.
• Subjects who have a supine heart rate at screening, after resting for 5 minutes outside the range of 40 - 90 beats/min.
• Subjects who have received any prescribed systemic or topical medication within two weeks prior to screening (although occasional use of paracetamol is permitted at the discretion of the investigator).
• Subjects who have received an investigational medicinal product within the previous four months (new chemical entity) or three months (licensed product) or subjects who have received a vaccine within three months preceding the start of dosing.
• Subjects who have donated any blood or plasma in the past month or in excess of 500 ml within twelve weeks preceding screening.
• Subjects who have a history of alcohol or drug abuse (consume greater than 28 units per week \[one unit of alcohol equals 250 ml of beer or lager or one glass of wine or 20 ml of spirits\]).
• Subjects with mental incapacity or language barriers which preclude adequate understanding.

Sponsors & Collaborators

• Sheffield Teaching Hospitals NHS Foundation Trust: lead
• British Heart Foundation: collaborator
• University of Sheffield: collaborator

Study Sites (1)

Sheffield Clinical Research Facility, Royal Hallamshire Hospital

Sheffield, S. Yorkshire, S10 2JF, United Kingdom

Location

MeSH Terms

Conditions

Coronary Artery Disease; Thrombosis

Interventions

Clopidogrel; Rifampin

Condition Hierarchy (Ancestors)

Coronary Disease; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Embolism and Thrombosis

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; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Robert F Storey

  University of Sheffield

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 4, 2008
• First Posted: June 12, 2008
• Study Start: November 1, 2007
• Primary Completion: March 1, 2008
• Study Completion: March 1, 2008
• Last Updated: June 12, 2008

Record last verified: 2008-06

Locations

GB (1)