Pharmacokinetic Interaction Between Ritonavir and Prasugrel in Healthy Volunteers

Healthy Volunteers Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01346800
• Other study ID #: MICRO-PRASU-RITONAVIR
• Status: Completed
• Phase: Phase 1
• First received: April 21, 2011
• Last updated: October 5, 2011
• Start date: February 2011
• Est. completion date: September 2011

Study information

• Verified date: April 2011
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: September 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• Prasugrel
Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4
• Ritonavir
Assessment of prasugrel metabolic ratio and phenotyping of CYP2B6/2C9/2C19/3A4 in presence of ritonavir

Locations

Country	Name	City	State
Switzerland	University Hospitals	Geneva 14

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Geneva

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	CYP2B6 phenotype in presence/absence of ritonavir	The phenotype will be assessed by taking a blood sample once and one week later	One week	No
Secondary	CYP2C9 phenotype in presence/absence of ritonavir	The phenotype will be assessed by taking a blood sample once and one week later	one week	No
Secondary	CYP2C19 phenotype in presence/absence of ritonavir	The phenotype will be assessed by taking a blood sample once and one week later	one week	No
Secondary	CYP3A4 phenotype in presence/absence of ritonavir	The phenotype will be assessed by taking a blood sample once and one week later	one week	No