HIV InfectionsPhase 2NCT00122577
Efficacy and Safety of Tenofovir DF/Atazanavir Enhanced With Low Dose of Ritonavir in HIV-Infected Patients
A Phase 2 study testing Tenofovir, Atazanavir and Ritonavir in people with HIV Infections, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Tenofovir, Atazanavir and Ritonavir
- How many people
- 50 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2002to Jul 2004
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
France1 site
Service d'Immunologie clinique Hopital Europeen Georges Pompidou
Paris, 75015
About this study
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)
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.
Read the 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
- Conditions
- HIV Infections
- Being tested
- Tenofovir, Atazanavir, Ritonavir
- Keywords
- HIV infections, Treatment Failure, tenofovir, atazanavir
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TenofovirDrug
AtazanavirDrug
RitonavirDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma HIV RNA level and percentage of patients with undetectable HIV-RNA in plasma at Week 26
Secondary outcomes (7)
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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2005 (estimated)
- Study startMar 2002
- Study completionJul 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants
Sponsor and investigators
- Lead sponsor
- French National Agency for Research on AIDS and Viral Hepatitis
- Sponsor type
- Other government
- Collaborators
- Bristol-Myers Squibb, Gilead Sciences
- Investigators
- Christophe Piketty, MD, Principal investigator, Hopital Européen Georges Pompidou Paris, service d'immunologie cliniqueJean Pierre Aboulker, MD, Study chair, Inserm SC10
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00122577
- Sponsor's protocol ID
- ANRS 107 Puzzle 2
- Status last verified
- Jul 2005
- First submitted
- 19 Jul 2005
- Last updated
- 28 Jul 2005
- Results posted
- No
Publications
Piketty C, Gerard L, Chazallon C, Calvez V, Clavel F, Taburet AM, Girard PM, Aboulker JP; ANRS 107 Puzzle 2 Study Group. Virological and immunological impact of non-nucleoside reverse transcriptase inhibitor withdrawal in HIV-infected patients with multiple treatment failures. AIDS. 2004 Jul 2;18(10):1469-71. doi: 10.1097/01.aids.0000131340.68666.21.
PubMed 15199325Taburet AM, Piketty C, Chazallon C, Vincent I, Gerard L, Calvez V, Clavel F, Aboulker JP, Girard PM. Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2004 Jun;48(6):2091-6. doi: 10.1128/AAC.48.6.2091-2096.2004.
PubMed 15155205
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT00122577
- Acronym / sponsor ID
- ANRS 107 Puzzle 2
- Conditions
- HIV Infections
- Keywords
- HIV infections, Treatment Failure, tenofovir, atazanavir
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 50 participants
- Lead sponsor
- French National Agency for Research on AIDS and Viral HepatitisOther government
- Collaborators
- Bristol-Myers Squibb, Gilead Sciences
- Study start
- Mar 2002
- Study completion
- Jul 2004
- First posted
- 22 Jul 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Tenofovir | Drug | – |
| Atazanavir | Drug | – |
| Ritonavir | Drug | – |
Primary outcome
Change in plasma HIV RNA level and percentage of patients with undetectable HIV-RNA in plasma at Week 26
7 secondary outcomes
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)
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2005.
- Results publication: PubMed 15199325Piketty C, Gerard L, Chazallon C, Calvez V, Clavel F, Taburet AM, Girard PM, Aboulker JP; ANRS 107 Puzzle 2 Study Group. Virological and immunological impact of non-nucleoside reverse transcriptase inhibitor withdrawal in HIV-infected patients with multiple treatment failures. AIDS. 2004 Jul 2;18(10):1469-71. doi: 10.1097/01.aids.0000131340.68666.21.
- Results publication: PubMed 15155205Taburet AM, Piketty C, Chazallon C, Vincent I, Gerard L, Calvez V, Clavel F, Aboulker JP, Girard PM. Interactions between atazanavir-ritonavir and tenofovir in heavily pretreated human immunodeficiency virus-infected patients. Antimicrob Agents Chemother. 2004 Jun;48(6):2091-6. doi: 10.1128/AAC.48.6.2091-2096.2004.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christophe Piketty, MD principal investigator
Hopital Européen Georges Pompidou Paris, service d'immunologie clinique
Jean Pierre Aboulker, MD study chair
Inserm SC10
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Tenofovir, Atazanavir and Ritonavir in people with HIV Infections, run by French National Agency for Research on AIDS and Viral Hepatitis at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 28 Jul 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma HIV RNA level and percentage of patients with undetectable HIV-RNA in plasma at Week 26. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00122577, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2005.