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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Tenofovir
Drug: Atazanavir
Drug: Ritonavir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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)

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

Primary Outcome Measures:
  • Change in plasma HIV RNA level and percentage of patients with undetectable HIV-RNA in plasma at Week 26

Secondary Outcome Measures:
  • 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)

Estimated Enrollment: 50
Study Start Date: March 2002
Estimated Study Completion Date: July 2004
Detailed Description:

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00122577

Locations
France
Service d'Immunologie clinique Hopital Europeen Georges Pompidou
Paris, France, 75015
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Bristol-Myers Squibb
Gilead Sciences
Investigators
Principal Investigator: Christophe Piketty, MD Hopital Européen Georges Pompidou Paris, service d'immunologie clinique
Study Chair: Jean Pierre Aboulker, MD Inserm SC10
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00122577     History of Changes
Other Study ID Numbers: ANRS 107 Puzzle 2
Study First Received: July 19, 2005
Last Updated: July 27, 2005
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
HIV infections
Treatment Failure
tenofovir
atazanavir

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Atazanavir
Tenofovir
Tenofovir disoproxil
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on April 16, 2014