IMPACT/R: Impact of Antiretroviral Treatment on Pharmacokinetics and Pharmacodynamics of Thienopyridines in Healthy Volunteers and HIV Patients

Sponsor

Jules Desmeules (Other)

Overall Status

Terminated

CT.gov ID

NCT03054207

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hiv	Drug: Clopidogrel 300Mg Tablet Drug: Prasugrel 60Mg	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Study Start Date :

Jun 1, 2015

Actual Primary Completion Date :

Apr 1, 2017

Actual Study Completion Date :

Apr 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: HIV clopidogrel clopidogrel 300 mg single dose oral route	Drug: Clopidogrel 300Mg Tablet
Experimental: HIV prasugrel prasugrel 60 mg single dose oral route	Drug: Prasugrel 60Mg
Active Comparator: Control clopidogrel clopidogrel 300 mg single dose oral route	Drug: Clopidogrel 300Mg Tablet
Active Comparator: Control prasugrel prasugrel 60 mg single dose oral route	Drug: Prasugrel 60Mg

Outcome Measures

Primary Outcome Measures

Comparison of Platelet Reactivity Index between HIV patients and healthy volunteers [4hr]
assess the effect of antiretroviral therapies on the response to antiplatelet treatment

Secondary Outcome Measures

Comparison of platelet inhibition between HIV patients and healthy volunteers [4hr]
Comparison of AUC of plasmatic concentrations of prasugrel and clopidogrel between HIV patients and healthy volunteers [4 hr]
Comparison of Cmax of prasugrel and clopidogrel between HIV patients and healthy volunteers [4 hr]
Comparison of Tmax of plasmatic concentrations of prasugrel and clopidogrelpatients and healthy between HIV patients and healthy volunteersvolunteers [4 hr]
Comparison of Half life of prasugrel and clopidogrel between HIV patients and healthy volunteers [4 hr]
Comparison of Clearance of prasugrel and clopidogrel between HIV patients and healthy volunteers [4 hr]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals	Geneva		Switzerland	1211

Sponsors and Collaborators

Jules Desmeules

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jules Desmeules, Professor, University Hospital, Geneva

ClinicalTrials.gov Identifier:

NCT03054207

Other Study ID Numbers:

13-096

First Posted:

Feb 15, 2017

Last Update Posted:

Sep 11, 2017

Last Verified:

Feb 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Additional relevant MeSH terms:

Clopidogrel

Prasugrel Hydrochloride

Study Results

No Results Posted as of Sep 11, 2017