Efficacy and Safety of Tenofovir DF/Atazanavir Enhanced With Low Dose of Ritonavir in HIV-Infected Patients

This study has been terminated.
Sponsor:
Collaborators:
Bristol-Myers Squibb
Gilead Sciences
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00122577
First received: July 19, 2005
Last updated: July 27, 2005
Last verified: July 2005

July 19, 2005
July 27, 2005
March 2002
Not Provided
Change in plasma HIV RNA level and percentage of patients with undetectable HIV-RNA in plasma at Week 26
Same as current
Complete list of historical versions of study NCT00122577 on ClinicalTrials.gov Archive Site
  • Tolerance during the study
  • Changes in CD4+ counts at week 26
  • Emergence of drug-resistant viruses
  • Rate of virus decay in plasma in group 2 during the initial phase (14 days) of therapy according to baseline EC50 of atazanavir
  • Pharmacokinetic (PK) profile of atazanavir alone at day 14
  • Blood samples prior to drug administration (Cmin) and after drug administration on day 14 at +1h, +2h, +3h, +5h, +8h, and +24h in 10 patients of group 2
  • PK assessment on Week 6, of atazanavir, after 4 weeks of co-administration with tenofovir DF. (Blood samples prior to drug administration (Cmin) and after drug administration at +1h, +2h, +3h, +5h, +8h, and +24h in the same 10 patients of group 2)
  • Tolerance during the study
  • Changes in CD4+ counts at week 26
  • Emergence of drug-resistant viruses
  • Rate of virus decay in plasma in the group 2 during the initial phase (14 days) of therapy according to baseline EC50 of atazanavir
  • Pharmacokinetic (PK) profile of atazanavir alone at day 14
  • Blood samples prior to drug administration (Cmin) and after drug administration on day 14 at +1h, +2h, +3h, +5h, +8h, and +24h in 10 patient of group 2
  • PK assessment on Week 6, of atazanavir, after 4 weeks of co-administration with tenofovir DF. (Blood samples prior to drug administration (Cmin) and after drug administration at +1h, +2h, +3h, +5h, +8h, and +24h in the same 10 patient of group 2
Not Provided
Not Provided
 
Efficacy and Safety of Tenofovir DF/Atazanavir Enhanced With Low Dose of Ritonavir in HIV-Infected Patients
Randomized Open Label Study Assessing the Antiviral Activity, Toxicity and Pharmacologic Interaction of Tenofovir DF/Atazanavir Enhanced With Low Dose of Ritonavir as Part of a Salvage Regimen in HIV Infected Patients With Multiple Treatment Failures (ANRS 107 Trial PUZZLE 2)

This trial is aimed at studying the antiviral activity, toxicity and pharmacokinetic (PK) interactions of tenofovir DF and atazanavir enhanced with low dose of ritonavir given alone and then concomitantly as part of a salvage regimen to HIV patients with multiple failure, under conditions allowing to tease out the specific role of atazanavir combined with low dose of ritonavir.

When licensed, new drugs are widely used in patients failing antiretroviral therapy, including patients with multiple failures. In such patients, having multi-resistant virus, the introduction of one new drug only in the salvage regimen will infrequently result in undetectable virus load in the plasma. Tenofovir DF and atazanavir appear promising because of their pharmacokinetic profile, activity, safety and resistance properties. In addition, pharmacokinetic data in healthy volunteers suggest that atazanavir could be optimized by adding ritonavir at low dose. Thus, one may speculate that atazanavir pharmacokinetic and antiviral activity could be optimized by adding ritonavir at low dose in patients exhibiting high rate of protease inhibitor mutations.

This protocol is aimed at studying the antiviral activity, toxicity and PK interactions, of tenofovir DF and atazanavir enhanced with low dose of ritonavir given alone and then concomitantly as part of a salvage regimen to patients with multiple failure, under conditions allowing to tease out the specific role of atazanavir combined with low dose of ritonavir.

EKG abnormalities (increased PR and QTc intervals) were observed in normal volunteers treated with atazanavir, therefore EKG safety monitoring will be performed on all subjects during this study

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Tenofovir
  • Drug: Atazanavir
  • Drug: Ritonavir
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
50
July 2004
Not Provided

Inclusion Criteria:

  • Males and non pregnant females 18 years of age and older who have confirmed laboratory diagnosis of HIV infection and documented failure (plasma HIV RNA level over 10,000 copies/ml) to at least two protease inhibitors (ritonavir [RTV] must have been given at a dose over 400 mg twice a day (bid), in order to qualify for a protease inhibitor in this study) and one non-nucleoside reverse transcriptase inhibitor (NNRTI)
  • Ongoing antiretroviral therapy at inclusion without change within the last month
  • No threshold of CD4 cell count
  • Patients naive of atazanavir and tenofovir DF

Exclusion Criteria:

  • Cardiomyopathy
  • QTc interval over 450 msec and pause length over 3 seconds on screening EKG
  • Heart rate below 40 bpm
  • Third degree heart block, and clinical symptoms potentially related to heart block
  • Ongoing immunotherapy including IL2, interferon or HIV specific vaccine
  • Ongoing opportunistic infection
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00122577
ANRS 107 Puzzle 2
Not Provided
Not Provided
French National Agency for Research on AIDS and Viral Hepatitis
  • Bristol-Myers Squibb
  • Gilead Sciences
Principal Investigator: Christophe Piketty, MD Hopital Européen Georges Pompidou Paris, service d'immunologie clinique
Study Chair: Jean Pierre Aboulker, MD Inserm SC10
French National Agency for Research on AIDS and Viral Hepatitis
July 2005

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