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

This study has been completed.
Sponsor:
Information provided by:
Radboud University
ClinicalTrials.gov Identifier:
NCT00943540
First received: July 21, 2009
Last updated: January 7, 2011
Last verified: January 2011

July 21, 2009
January 7, 2011
July 2009
December 2010   (final data collection date for primary outcome measure)
pharmacokinetics of raltegravir [ Time Frame: after two weeks of reference treatment and after two weeks of test treatment ] [ Designated as safety issue: No ]
Same as current
Complete list of historical versions of study NCT00943540 on ClinicalTrials.gov Archive Site
  • Viral load [ Time Frame: after two weeks treatment with the reference treatment and after two weeks treatment with the test treatment ] [ Designated as safety issue: Yes ]
  • Adverse events [ Time Frame: entire trial ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Pharmacokinetic and Safety Study of Raltegravir and Atazanavir in a Once Daily Dose Regimen in HIV-1 Infected Patients
Pharmacokinetic and Safety Pilotstudy of RAltegravir and Atazanavir in a Once DAily Dose Regimen in HIV-1 Infected Patients (PRADA)

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.

Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • HIV Infection
  • HIV Infections
  • Drug: raltegravir QD
    Raltegravir 800mg QD
  • Drug: atazanavir
    atazanavir
  • Drug: lamivudine (or emtricitabine)
    lamivudine (or emtricitabine)
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
Interventions:
  • Drug: raltegravir QD
  • Drug: atazanavir
  • Drug: lamivudine (or emtricitabine)
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
20
January 2011
December 2010   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Germany,   Netherlands
 
NCT00943540
UMCN-AKF 08.07
No
D.M. Burger, PhD, PharmD, Radboud University Medical Centre Nijmegen
Radboud University
Not Provided
Principal Investigator: David Burger Radboud University
Radboud University
January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP