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

NCT ID: NCT00943540

Last Updated: 2020-11-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-07-31
• Study Completion Date: 2011-01-31

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.

Conditions

HIV Infection; HIV Infections

Keywords

pharmacokinetics; single dose; raltegravir; Treatment experienced

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

raltegravir QD

Intervention Type: DRUG

Raltegravir 800mg QD

atazanavir

Intervention Type: DRUG

atazanavir

lamivudine (or emtricitabine)

Intervention Type: DRUG

lamivudine (or emtricitabine)

Interventions

raltegravir QD

Raltegravir 800mg QD

Intervention Type: DRUG

atazanavir

atazanavir

Intervention Type: DRUG

lamivudine (or emtricitabine)

lamivudine (or emtricitabine)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Radboud University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Radboud University Medical Centre Nijmegen

Principal Investigators

David Burger

Role: PRINCIPAL_INVESTIGATOR

Radboud University Medical Center

Locations

University of Bonn

Bonn, , Germany

Rijnstate Hospital Arnhem

Arnhem, , Netherlands

Radboud University Medical Centre Nijmegen

Nijmegen, , Netherlands

Erasmus Medical Center Rotterdam

Rotterdam, , Netherlands

Countries

Germany; Netherlands

References

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.

Reference Type: RESULT

PMID: 23506243 (View on PubMed)

Other Identifiers

UMCN-AKF 08.07

Identifier Type: -

Identifier Source: org_study_id