Pharmacokinetic Interaction Between Ritonavir and Prasugrel in Healthy Volunteers

NCT01346800 | Completed Phase 1

• 1 other identifier: MICRO-PRASU-RITONAVIR
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

HIV patients are at particular risk to develop cardiovascular disease (CVD) as they exhibit multiple known risk factors for CVD. Of specific concern is the fact that use of the non nucleosidic reverse transcriptase inhibitors (NNRTI) and/or protease inhibitors (PI) drug classes is associated with dyslipidemia known to increase the risk of coronary heart disease particularly among older subjects with normalized CD4 cell counts and suppressed HIV replication. HIV patients could thus potentially receive anti-aggregant therapy concomitantly with their antiretroviral treatment. Prasugrel is an anti-aggregating agent indicated to prevent the recurrence of ischemic events after coronary arteries stenting. It is a pro-drug mainly metabolized by cytochromes P450 (CYP) 3A and 2B6 and to a lesser extent by CYP2C9 and 2C19. Ritonavir is an anti-protease and CYP3A4 and CYP2B6 inhibitor used in anti-HIV therapy. The aim of the present study is to assess the potential drug-drug interaction between prasugrel and the CYP3A/2B6 inhibitor ritonavir. Ten healthy volunteers will receive prasugrel 10mg alone or after 100mg ritonavir. The effect of ritonavir on prasugrel pharmacokinetics will be assessed. The two sessions will be separated by a one-week "wash out" period. During each session, CYP3A, 2B6, 2C9 and 2C19 activities will be assessed by a micrococktail approach with microdoses of midazolam, bupropion, flurbiprofen and omeprazole. The pharmacokinetics of prasugrel active metabolite will be assessed during the two sessions.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Plasmatic prasugrel metabolites concentrations (ng/mL) in presence/absence of ritonavir

  The concentrations will be measured at 9 differents times during 6 hours (0,1min,30min,1H,1H30,2H,3H,4H,6H). The measurements will be repeated one week later for 6 hours

  One week

Secondary Outcomes (4)

• CYP2B6 phenotype in presence/absence of ritonavir

  One week

• CYP2C9 phenotype in presence/absence of ritonavir

  one week

• CYP2C19 phenotype in presence/absence of ritonavir

  one week

• CYP3A4 phenotype in presence/absence of ritonavir

  one week

Study Arms (2)

Prasugrel 10mg po

EXPERIMENTAL

Drug: Prasugrel

Prasugrel 10mg po + ritonavir 100mg po

EXPERIMENTAL

Drug: Prasugrel; Drug: Ritonavir

Interventions

Prasugrel DRUG

Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4

Prasugrel 10mg po; Prasugrel 10mg po + ritonavir 100mg po

Ritonavir DRUG

Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4 in presence of ritonavir

Prasugrel 10mg po + ritonavir 100mg po

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male volunteers aged from 18 to 60 years
• BMI between 18 and 25
• Understanding of French language and able to give an inform consent.

You may not qualify if:

• smoker
• hypersensitivity to prasugrel or ritonavir or constituents of the tablets - - regular alcohol consumption
• concomitant disease
• intake of any drug or particular food (grapefruit) that can affect or metabolized by the CYP3A, 2C19, 2B6 and 2C9 within 1 month before the study
• 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)
• bleeding familial history or antecedent or haemorrhagic disease
• previous gastro-intestinal ulcer or active ulcer

Sponsors & Collaborators

• University Hospital, Geneva: lead

Study Sites (1)

University Hospitals

Geneva, 1211, Switzerland

Location

MeSH Terms

Interventions

Prasugrel Hydrochloride; Ritonavir

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Thiazoles; Azoles

Study Officials

• Jules A Desmeules, Pr

  University Hospital, Geneva

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: April 21, 2011
• First Posted: May 3, 2011
• Study Start: February 1, 2011
• Primary Completion: June 1, 2011
• Study Completion: September 1, 2011
• Last Updated: October 6, 2011

Record last verified: 2011-04

Locations

CH (1)