Impact of Antiretroviral Treatment on Pharmacokinetics and Pharmacodynamics of Thienopyridines in Healthy Volunteers and HIV Patients

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

21 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-06-30

Study Completion Date

2017-04-30

Brief Summary

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HIV patients are at particular risk to develop cardiovascular disease (CVD) as they exhibit multiple risk factors by the nature of their pathology. In addition, the long term exposition to antiretroviral drugs has been associated to an increased risk for CVD. HIV patients can thus potentially receive antiplatelet therapy concomitantly with their antiretroviral treatment. Clopidogrel and prasugrel are thienopyridine antiplatelet agents indicated to prevent the recurrence of ischemic events after coronary arteries stenting. These pro-drugs are mainly bioactivated by cytochromes P450 (CYP) 3A and 2B6 for prasugrel and CYP2C19, CYP3A and CYP2B6 for clopidogrel. Ritonavir is commonly used to "boost" the bioavailability of other HIV drugs through inhibition of CYP3A4 as well as CYP2B6 and CYP2C9. This interaction could therefore reduce clopidogrel and prasugrel efficacy by reducing the formation of their active metabolites. The aim of the present study is to assess the potential drug-drug interaction between clopidogrel/prasugrel and ritonavir. Two groups of 12 male subjects will be constituted (12 HIV patients under ritonavir boosted therapy and 12 healthy volunteers) in a randomized cross-over clinical trial. All subjects will also be genotyped for the CYP2C19. The pharmacokinetics of clopidogrel active metabolite and prasugrel active metabolite will be assessed. Furthermore, the pharmacodynamic response will be evaluated by two gold standard platelet inhibition tests, namely VAsodilator-Stimulated Phosphoprotein Assay (VASP) and VerifyNow® assays. The primary endpoint of this study is to compare the pharmacodynamic response to clopidogrel and prasugrel in HIV patients to that of healthy volunteers.

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Detailed Description

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Conditions

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Hiv

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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HIV clopidogrel

clopidogrel 300 mg single dose oral route

Group Type EXPERIMENTAL

Clopidogrel 300Mg Tablet

Intervention Type DRUG

HIV prasugrel

prasugrel 60 mg single dose oral route

Group Type EXPERIMENTAL

Prasugrel 60Mg

Intervention Type DRUG

Control clopidogrel

clopidogrel 300 mg single dose oral route

Group Type ACTIVE_COMPARATOR

Clopidogrel 300Mg Tablet

Intervention Type DRUG

Control prasugrel

prasugrel 60 mg single dose oral route

Group Type ACTIVE_COMPARATOR

Prasugrel 60Mg

Intervention Type DRUG

Interventions

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Clopidogrel 300Mg Tablet

Intervention Type DRUG

Prasugrel 60Mg

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Healthy males \>18 years
* Understanding of French language and able to give an inform consent
* Anti-HIV therapy with ritonavir or cobicistat (for HIV group)
* Stable antiretroviral treatment since at least 2 weeks (for HIV group)
* Viremia \<100 copies/ml (for HIV group)

Exclusion Criteria

* renal failure: calculated creatinine Clearance (cockcroft) \< 50ml/min
* hepatic impairment (ASAT, ALAT, bilirubin, gamma-GT more than 2-fold increase)
* smoker \>1 pack/day
* hypersensitivity to any of the drugs used
* intake of any drug or particular food (grapefruit) that can affect CYP activities inhibitors (in the last 10 days before the start of the study or 4 half-life after the last intake)
* pathologies or drugs associated with an increased bleeding risk such as aspirin, non-steroidal anti-inflammatory drugs, steroids and serotonin reuptake inhibitors (in the last 10 days before the start of the study or 4 half-life after the last intake)
* bleeding familial history or antecedent or haemorrhagic disease

Minimum Eligible Age

18 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes