Clinical trial NCT00943540: Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients
Official title: Pharmacokinetic and Safety Pilotstudy of RAltegravir and Atazanavir in a Once DAily Dose Regimen in HIV-1 Infected Patients (PRADA)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infection
HIV Infections
Keywords: pharmacokinetics
single dose
raltegravir
Treatment experienced
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2009-07-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: pharmacokinetics of raltegravir
timeFrame: after two weeks of reference treatment and after two weeks of test treatment
Secondary outcomes:
measure: Viral load
timeFrame: after two weeks treatment with the reference treatment and after two weeks treatment with the test treatment
measure: Adverse events
timeFrame: entire trial
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: University of Bonn
city: Arnhem
country: Netherlands
facility: Rijnstate Hospital Arnhem
city: Nijmegen
country: Netherlands
facility: Radboud University Medical Centre Nijmegen
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center Rotterdam
Study officials:
affiliation: Radboud University Medical Center
name: David Burger
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jansen A, Colbers EP, van der Ven AJ, Richter C, Rockstroh JK, Wasmuth JC, van Luin M, Burger DM. Pharmacokinetics of the combination raltegravir/atazanavir in HIV-1-infected patients. HIV Med. 2013 Aug;14(7):449-52. doi: 10.1111/hiv.12029. Epub 2013 Mar 18.