PRADA: Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients

Sponsor

Radboud University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT00943540

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The licensed dose of raltegravir is 400 mg twice daily with or without food. Raltegravir is metabolized predominantly through glucuronidation by UGT1A1. Atazanavir increases the plasma concentrations of raltegravir 400 mg twice daily by 72% due to inhibition of UGT 1A1.

This suggests that combined use of atazanavir and a lower dose frequency of raltegravir, once daily for example, is possible. Another reason why raltegravir most likely can be applied is that its pharmacodynamic effect is not related to Cmin but to AUC which is expected to be similar for an 800mg QD dose when compared to 400mg BD. Phase III clinical trials evaluating QD dosing of raltegravir are currently ongoing and interim results are expected to be published in mid 2009.

A regimen of atazanavir and raltegravir in combination with lamivudine or emtricitabine may be a well tolerated and effective NNRTI-, and ritonavir-sparing regimen that could be an attractive option for both first and second line (after NRTI/NNRTI failure) treatment regimens.

Condition or Disease	Intervention/Treatment	Phase
HIV Infection HIV Infections	Drug: raltegravir QD Drug: atazanavir Drug: lamivudine (or emtricitabine)	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Pharmacokinetic and Safety Pilotstudy of RAltegravir and Atazanavir in a Once DAily Dose Regimen in HIV-1 Infected Patients (PRADA)

Study Start Date :

Jul 1, 2009

Actual Primary Completion Date :

Dec 1, 2010

Actual Study Completion Date :

Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Raltegravir BID-QD Week 1-4 600 mg of atazanavir to be taken once daily 400 mg of raltegravir to be taken twice daily 300 mg of lamivudine (or 200 mg of emtricitabine) to be taken once daily Week 5-8 600 mg of atazanavir to be taken once daily 800 mg of raltegravir to be taken once daily 300 mg of lamivudine (or 200 mg of emtricitabine) to be taken once daily	Drug: raltegravir QD Raltegravir 800mg QD Drug: atazanavir atazanavir Drug: lamivudine (or emtricitabine) lamivudine (or emtricitabine)

Arm

Intervention/Treatment

Experimental: Raltegravir BID-QD

Week 1-4 600 mg of atazanavir to be taken once daily 400 mg of raltegravir to be taken twice daily 300 mg of lamivudine (or 200 mg of emtricitabine) to be taken once daily Week 5-8 600 mg of atazanavir to be taken once daily 800 mg of raltegravir to be taken once daily 300 mg of lamivudine (or 200 mg of emtricitabine) to be taken once daily

Drug: raltegravir QD

Raltegravir 800mg QD

Drug: atazanavir

atazanavir

Drug: lamivudine (or emtricitabine)

lamivudine (or emtricitabine)

Outcome Measures

Primary Outcome Measures

pharmacokinetics of raltegravir [after two weeks of reference treatment and after two weeks of test treatment]

Secondary Outcome Measures

Viral load [after two weeks treatment with the reference treatment and after two weeks treatment with the test treatment]
Adverse events [entire trial]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

HIV-infected as documented by positive HIV antibody test and confirmed by Western Blot.
Subject is at least 18 years of age at the day of screening.
Subject is able and willing to sign the Informed Consent Form prior to screening evaluations.
HIV-1 RNA < 40 copies/mL for at least 6 months on antiretroviral therapy.
Subject has no history of previous virological failure or documented resistance mutations

Exclusion Criteria:

History of sensitivity/idiosyncrasy to the drug or chemically related compounds or excipients, which may be employed in the trial.
Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion.
Inability to understand the nature and extent of the trial and the procedures required.
Pregnant female (as confirmed by an HCG test performed less than 3 weeks before the first dose) or breast-feeding female.
Abnormal serum transaminases determined as levels being > 5 times upper limit of normal (see Appendix A for normal ranges of clinical laboratory values).
Concomitant use of medications that interfere with raltegravir or atazanavir pharmacokinetics: rifampicin, irinotecan, midazolam, triazolam, ergotamine, dihydroergotamine, cisapride, pimozide, lovastatin, simvastatin, indinavir, proton pump inhibitors, H2 receptor antagonists, St. john's wort, Ginkgo Biloba, didanosine, tenofovir, efavirenz, nevirapine, antacids, clarithromycin, phenytoin, phenobarbital, carbamazepine.
Active hepatobiliary or hepatic disease (including chronic hepatitis B infection).
Alcohol abuse.

Contacts and Locations

Locations

	Site	City	Country
1	University of Bonn	Bonn	Germany
2	Rijnstate Hospital Arnhem	Arnhem	Netherlands
3	Radboud University Medical Centre Nijmegen	Nijmegen	Netherlands
4	Erasmus Medical Center Rotterdam	Rotterdam	Netherlands