Pharmacokinetic Interaction Between Ritonavir and Prasugrel in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by:
University Hospital, Geneva
ClinicalTrials.gov Identifier:
NCT01346800
First received: April 21, 2011
Last updated: October 5, 2011
Last verified: April 2011
  Purpose

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.


Condition Intervention Phase
Healthy Volunteers
Drug: Prasugrel
Drug: Ritonavir
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Basic Science

Resource links provided by NLM:


Further study details as provided by University Hospital, Geneva:

Primary Outcome Measures:
  • Plasmatic prasugrel metabolites concentrations (ng/mL) in presence/absence of ritonavir [ Time Frame: One week ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • CYP2B6 phenotype in presence/absence of ritonavir [ Time Frame: One week ] [ Designated as safety issue: No ]
    The phenotype will be assessed by taking a blood sample once and one week later

  • CYP2C9 phenotype in presence/absence of ritonavir [ Time Frame: one week ] [ Designated as safety issue: No ]
    The phenotype will be assessed by taking a blood sample once and one week later

  • CYP2C19 phenotype in presence/absence of ritonavir [ Time Frame: one week ] [ Designated as safety issue: No ]
    The phenotype will be assessed by taking a blood sample once and one week later

  • CYP3A4 phenotype in presence/absence of ritonavir [ Time Frame: one week ] [ Designated as safety issue: No ]
    The phenotype will be assessed by taking a blood sample once and one week later


Enrollment: 10
Study Start Date: February 2011
Study Completion Date: September 2011
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Prasugrel 10mg po Drug: Prasugrel
Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4
Experimental: Prasugrel 10mg po + ritonavir 100mg po Drug: Prasugrel
Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4
Drug: Ritonavir
Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4 in presence of ritonavir

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01346800

Locations
Switzerland
University Hospitals
Geneva 14, Switzerland, 1211
Sponsors and Collaborators
University Hospital, Geneva
Investigators
Principal Investigator: Jules A Desmeules, Pr University Hospitals, Geneva
  More Information

No publications provided

Responsible Party: Pr Jules Desmeules, University Hospitals, Geneva
ClinicalTrials.gov Identifier: NCT01346800     History of Changes
Other Study ID Numbers: MICRO-PRASU-RITONAVIR
Study First Received: April 21, 2011
Last Updated: October 5, 2011
Health Authority: Switzerland: Swissmedic

Additional relevant MeSH terms:
Ritonavir
Prasugrel
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 20, 2014