HIV InfectionsPhase 3NCT00035932
Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV
A Phase 3 study testing Atazanavir + ritonavir + tenofovir + nucleoside, Atazanavir + saquinavir + tenofovir + nucleoside and Lopinavir/ritonavir + tenofovir + nucleoside in people with HIV Infections, run by Bristol-Myers Squibb at 29 sites in United States.
Trial summary
The purpose of this study is to learn how well atazanavir (ATV) works in combination with ritonavir (RTV) or saquinavir (SQV) with tenofovir (TDF) and a nucleoside to reduce the viral load of treatment experienced subjects with human immunodeficiency virus (HIV). Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- HIV Infections
- What is being tested?
- Atazanavir + ritonavir + tenofovir + nucleoside, Atazanavir + saquinavir + tenofovir + nucleoside and Lopinavir/ritonavir + tenofovir + nucleoside
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 571 participants
- Where
- 29 sitesUnited States
- Study dates
- Nov 2001to Mar 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Virologic failure to 2 or more highly active antiretroviral therapy (HAART) regimens that, in total, have included at least one drug from all approved classes protease inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (PI, NNRTI, NRTI):
- Currently on a failing HAART regimen with 2 qualifying plasma viral load measurements (hospital/clinic value within 4 weeks of screening with viral load equivalent to =>1,000 c/mL on the Roche Amplicor[TM] and central lab measurements of =>1,000 c/mL (Roche Amplicor[TM]) within 4 weeks of randomization
- Cluster of Differentiation 4 (CD4) cell count =>50 cells/mm3 obtained within 4 weeks prior to randomization
- =>16 years of age (or minimum age as determined by local regulations or as legal requirements dictate);
- History of prior virologic response to at least one HAART regimen, defined as a 1.0 log10 decline or a decline in viral load to <400 c/mL by Roche Amplicor or <500 c/mL by Chiron Quantiplex branched DNA (bDNA) assay
- Both females of child bearing potential and males must utilize effective barrier contraception to reduce transmission of sexually transmitted disease, including human immunodeficiency virus (HIV). Other contraception in addition to barrier methods is permitted; interaction between atazanavir and oral contraceptives has not been studied.
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- Subjects must be able to provide written informed consent;
- Subjects should be available for follow-up for a period of at least 48 weeks
- Baseline laboratory values measured within 2 weeks prior to initiating study drugs as follows:
- serum creatine <1.5 times the upper limit of normal (ULN)
- total serum lipase <1.4 times the ULN
- liver enzymes alanine aminotransferase (AST), aspartate aminotransferase (ALT) <3 times the ULN
- total serum bilirubin <1.5 times the ULN
Who cannot join
- Prior use (=>3 days) of atazanavir, TVF or LPV/RTV; if history of SQV, then must be phenotypically sensitive
- the current failing antiretroviral regimen must have been administered for at least eight weeks at he initiation of screening and must not include both a PI and NNRTI
- Presence of a newly diagnosed HIV-related opportunistic infection or any medical requiring acute therapy at the time of enrollment
- Proven or suspected acute hepatitis in the 30 days prior to study entry. Subjects with chronic hepatitis are eligible provided that their liver function enzymes (ALT/AST) are <3 x ULN
- Previous therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatoxic, hepatoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment of therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect Cytochrome P450 3A4 (CYP3A4).
- Active alcohol or substance use sufficient, in the Investigator's opinion, to prevent adequate compliance with study therapy or to increase the risk of developing pancreatitis or chemical hepatitis
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- Intractable diarrhea (=> 6 loose stools/day for at least 7 days consecutive days) within 30 days prior to study entry
- Pregnancy or breast-feeding
- History of hemophilia
- Presence of cardiomyopathy
- Any one of the following:
- Heart rate-corrected QT (QTc) interval >450 msec on the screening electrocardiogram (EKG)
- Heart rate <40 beats per minute (bpm)
- Pause length >3 seconds seen on EKG
- Clinical symptoms potentially related to heart block
- Third degree heart block
- History of acute or chronic pancreatitis
- If choosing 2'-3' dideoxyinosine (ddI) or 2',3'-didehydro-3'-deoxythymidine (d4T) as the NRTI: History or signs and symptoms of bilateral peripheral neuropathy => Grade 2 at the time of screening
- Inability to tolerate oral medications
- Any other clinical conditions or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for study or unable to comply with the dosing requirements.
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
United States29 sites
Study site
Akron, Ohio
Study site
Altamonte Springs, Florida
Study site
Boise, Indiana
Study site
Boulder, Colorado, 80304
Study site
Brookline, Massachusetts
Study site
Buffalo, New York, 14215
Study site
Dallas, Texas, 75246
Study site
Dallas, Texas
Study site
Decatur, Georgia
Study site
East Orange, New Jersey
Study site
Fall River, Massachusetts, 02720
Study site
Fort Lauderdale, Florida, 33306
Study site
Fort Lauderdale, Florida, 33308
Study site
Honolulu, Hawaii, 96816
Study site
Houston, Texas, 77006
Study site
Huntersville, North Carolina, 28078
Study site
Louisville, Kentucky, 40202
Study site
Manhasset, New York, 11030
Study site
Miami Beach, Florida, 33160
Study site
New Orleans, Louisiana
Study site
New York, New York, 10019
Study site
Newark, New Jersey, 07103
Study site
Orlando, Florida, 32801
Study site
Rochester, New York, 14620
Study site
San Francisco, California, 94121
Study site
Torrance, California, 90502
Study site
Wichita, Kansas, 67214
Study site
Winston-Salem, North Carolina, 27157
Study site
Winston-Salem, North Carolina, 29203
About this study
Official title: Phase III Open Label Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV
The purpose of this study is to learn how well atazanavir (ATV) works in combination with ritonavir (RTV) or saquinavir (SQV) with tenofovir (TDF) and a nucleoside to reduce the viral load of treatment experienced subjects with human immunodeficiency virus (HIV). There is a comparison arm with lopinavir (LPV)/RTV and TDF and a nucleoside.
- Conditions
- HIV Infections
- Being tested
- Atazanavir + ritonavir + tenofovir + nucleoside, Atazanavir + saquinavir + tenofovir + nucleoside, Lopinavir/ritonavir + tenofovir + nucleoside
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atazanavir + ritonavir + tenofovir + nucleosideDrug
Also called BMS-232632, Reyataz
Active Comparator, Capsules, tablets, Oral
Atazanavir + saquinavir + tenofovir + nucleosideDrug
Also called BMS-232632, Reyataz
Active Comparator, Capsules, tablets, Oral
Lopinavir/ritonavir + tenofovir + nucleosideDrug
Active Comparator, Capsules, tablets, Oral
| Study group | Role | What they receive |
|---|---|---|
| I | Active comparator | ATV 300 mg + RTV 100 mg + TDF 300 mg + nucleoside of choice
ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study Receives: Drug: Atazanavir + ritonavir + tenofovir + nucleoside |
| II | Active comparator | ATV 400 mg + SQV 1200 mg + TDF 300 mg + nucleoside of choice
ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study Receives: Drug: Atazanavir + saquinavir + tenofovir + nucleoside |
| III | Active comparator | LPV/RTV 400/100 mg + TDF 300 mg + nucleoside of choice
LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study Receives: Drug: Lopinavir/ritonavir + tenofovir + nucleoside |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24
Measured: Baseline, Week 24
Mean Change From Baseline in HIV RNA at Week 48
Measured: Baseline, Week 48
Mean Change From Baseline in HIV RNA at Week 96
Measured: Baseline, Week 96
Secondary outcomes (42)
Mean Change From Baseline in HIV RNA at Week 2
Measured: Baseline, Week 2
Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity)
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 400 c/mL at Week 24, by their baseline phenotypic sensitivity to their randomized PI.
Measured: Baseline, Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity)
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 400 c/mL at Week 48, by their baseline phenotypic sensitivity to their randomized PI.
Measured: Baseline, Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 400 c/mL at Week 96.
Measured: Baseline, Week 96
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24
Measured: Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24, by PI Sensitivity
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 50 c/mL at Week 24, by their baseline phenotypic sensitivity to their randomized PI.
Measured: Baseline, Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48
Measured: Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48, by PI Sensitivity
Number of participants with a >=0.5 log10 decrease in HIV RNA from baseline or HIV RNA < 50 c/mL at Week 48, by their baseline phenotypic sensitivity to their randomized PI.
Measured: Baseline, Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96
Measured: Week 96
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Measured: Week 24
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Measured: Week 48
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96
Treatment Response = confirmed suppression to LOQ (400 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Measured: Week 96
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Measured: Week 24
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Measured: Week 48
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96
Treatment Response = confirmed suppression to LOQ (50 c/mL). The Algorithm for Treatment Response Without Prior Failure (TRPWF) = participants staying in response at the analysis timepoint without having an intervening, confirmed rebound.
Measured: Week 96
Change From Baseline in CD4 Cell Count at Week 24
Measured: Baseline, Week 24
Change From Baseline in CD4 Cell Count at Week 48
Measured: Baseline, Week 48
Change From Baseline in CD4 Cell Count at Week 96
Measured: Baseline, Week 96
Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with HIV RNA change from baseline at Week 24 were explored.
Measured: Baseline, Week 24
Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 48
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with HIV RNA change from baseline at Week 48 were explored.
Measured: Baseline, Week 48
Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with CD4 cell count change from baseline at Week 24 were explored.
Measured: Baseline, Week 24
Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 48
Pearson correlations of the Cmin (trough plasma concentration), IQ (the ratio of Cmin of ATV to HIV IC50), and Number of baseline PI Mutations with CD4 cell count change from baseline at Week 48 were explored.
Measured: Baseline, Week 48
Lipid Mean Percent Change From Baseline at Week 24
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Measured: Baseline, Week 24
Lipid Mean Percent Change From Baseline at Week 48
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Measured: Week 48
Lipid Mean Percent Change From Baseline at Week 96, Observed Values
Mean percent change in total cholesterol, high density lipoprotein (HDL) cholesterol, fasting low density lipoprotein (LDL) cholesterol, and fasting triglycerides.
Measured: Week 96
Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48
AE=any new untoward medical occurrence/worsening of a pre-existing medical condition regardless of causal relationship. SAE=any untoward medical occurrence at any dose that: results in death; is life-threatening; requires/prolongs inpatient hospitalization; results in persistent/significant disability; is cancer; is congenital anomaly/birth defect; results in drug dependency/abuse; is an important medical event.
Measured: From Enrollment through Week 48
Most Common AEs and AEs of Interest Through Week 48
Prespecified AEs of interest included jaundice, ocular icterus, and hyperbilirubinemia.
Measured: From Enrollment to Week 48
Fasting Glucose Mean Change From Baseline at Week 24
Measured: Baseline, Week 24
Fasting Glucose Mean Change From Baseline at Week 48
Measured: Week 48
Grade 3/4 Laboratory Abnormalities Through Week 48
Common Terminology Criteria for Adverse Events v3.0 (CTCAE) Grades:1=Mild, 2=Moderate, 3=Severe, 4=Life-threatening/disabling, 5=Death. Abnormal values: absolute neutrophil count: ≥500 to <750/mm3 (grade 3), <500/mm3 (grade 4); platelets: 20,000-49,999/mm3 (grade 3), <20,000/mm3 or diffuse petechiae (grade 4); alanine transaminase (ALT): 5.1-10 x upper limit of normal (ULN; grade 3), >10 x ULN (grade 4); aspartate transaminase (AST): 5.1-10 x ULN (grade 3), >10 x ULN (grade 4); bilirubin: 2.6-5 x ULN (grade 3), >5 x ULN (grade 4).
Measured: From Enrollment to Week 48
Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point
The QT interval is a measure of the time between the start of the Q wave and the end of the T wave in the heart's electrical cycle. The QT interval was corrected for heart rate using Fridericia's (QTcF) formula.
Measured: Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
PR Interval and Change From Baseline by Analysis Time Point
The PR interval is measured from the beginning of the P wave to the beginning of the QRS complex, and reflects the time the electrical impulse takes to travel from the sinus node through the atrioventricular (AV) node and entering the ventricles. The PR interval is therefore a good estimate of AV node function.
Measured: Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire
The MACS adherence questionnaire asks patients how many medication doses they missed during the previous day, 2 days, 3 days and 4 days. Drug-specific questions included adherence with dose and frequency. Adherence was defined as taking all doses and numbers of pills as prescribed for each medication. This strict adherence cut-off was based on the guidelines stating that anything less than excellent adherence may result in a virus breakthrough and development of resistance.
Measured: Baseline, Week 24, Week 48
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)
The EQ-5D is a 5-item questionnaire to assess health-related quality of life in 5 health dimensions (mobility, self-care, usual activity, pain/discomfort, anxiety/depression) are scored on a 3-level scale: no problems (1), some problems (2), extreme problems (3). Using a standard algorithm, responses are summarized into a single score, the EQ-5D Health Index Score (HIS), which ranges between 1 (representing perfect health) and 0 (representing the worst imaginable health state or death). The smallest coefficient of change is 0.03.
Measured: Baseline, Week 24, Week 48
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48)
The EQ-5D has a Visual Analog Scale (VAS), which is a feeling thermometer-like scale with a range between 0 and 100. Patients are required to draw a line from a box on the VAS scale to an actual mark on the thermometer-like scale that corresponds with a number that reflects their self-assessed health status at the time they are completing the questionnaire. Higher VAS scores indicate better overall health. There is no minimum clinically important difference reported in the literature for VAS.
Measured: Baseline, Week 24, Week 48
Number of Participants Utilizing Resources for Managing Lipid Elevation
Participants' overall resource utilization for managing lipid elevation that includes the management of side effects of lipid lowering medications, such as those due to drug interactions.
Measured: Baseline, Week 24, Week 48
Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values
The minimum or "trough" concentration (Cmin) of a drug observed after its administration and just prior to the administration of a subsequent dose.
Measured: collected at the pre-dose time point after receiving atazanavir for at least four weeks
HIV IC50 at Week 24
IC50: inhibitory concentration of drug required to reduce viral replication by 50%.
Measured: Week 24
Inhibitory Quotient at Week 24
Inhibitory quotient is a measure of drug exposure and susceptibility in an individual. The IQ is typically calculated as the ratio of Cmin to HIV IC50.
Measured: Baseline, Week 24
Inhibitory Quotient at Week 48
Inhibitory quotient is a measure of drug exposure and susceptibility in an individual. The IQ is typically calculated as the ratio of Cmin to HIV IC50.
Measured: Baseline, Week 48
HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24
Week 24 HIV RNA level and change from baseline were summarized for treated subjects with evaluable Cmins.
Measured: Baseline, Week 24
HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 48
Week 24 HIV RNA level and change from baseline were summarized for treated subjects with evaluable Cmins.
Measured: Baseline, Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2002 (estimated)
- Study startNov 2001
- Primary completionJul 2003
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 571 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00035932
- Sponsor's protocol ID
- AI424-045
- Status last verified
- Nov 2010
- First submitted
- 6 May 2002
- Last updated
- 24 Dec 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Expanded access
- Available
Study at a glance
From the registry record, last updated by the sponsor on 24 Dec 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase III Open Label Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV
- ClinicalTrials.gov ID
- NCT00035932
- Acronym / sponsor ID
- AI424-045
- Conditions
- HIV Infections
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 571 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Nov 2001
- Primary completion
- Jul 2003 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 8 May 2002 (estimated)
- Results
- Posted 24 Dec 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to learn how well atazanavir (ATV) works in combination with ritonavir (RTV) or saquinavir (SQV) with tenofovir (TDF) and a nucleoside to reduce the viral load of treatment experienced subjects with human immunodeficiency virus (HIV). There is a comparison arm with lopinavir (LPV)/RTV and TDF and a nucleoside.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| I | Active comparator | Drug: Atazanavir + ritonavir + tenofovir + nucleosideATV 300 mg + RTV 100 mg + TDF 300 mg + nucleoside of choice ATV , RTV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study |
| II | Active comparator | Drug: Atazanavir + saquinavir + tenofovir + nucleosideATV 400 mg + SQV 1200 mg + TDF 300 mg + nucleoside of choice ATV, SQV, and TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study |
| III | Active comparator | Drug: Lopinavir/ritonavir + tenofovir + nucleosideLPV/RTV 400/100 mg + TDF 300 mg + nucleoside of choice LPV/RTV twice daily, TDF once daily, nucleoside per label 48 Weeks and then for as long as subject is in need of therapy through study |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- Virologic failure to 2 or more highly active antiretroviral therapy (HAART) regimens that, in total, have included at least one drug from all approved classes protease inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (PI, NNRTI, NRTI):
- =>16 years of age (or minimum age as determined by local regulations or as legal requirements dictate);
- History of prior virologic response to at least one HAART regimen, defined as a 1.0 log10 decline or a decline in viral load to <400 c/mL by Roche Amplicor or <500 c/mL by Chiron Quantiplex branched DNA (bDNA) assay
- Both females of child bearing potential and males must utilize effective barrier contraception to reduce transmission of sexually transmitted disease, including human immunodeficiency virus (HIV). Other contraception in addition to barrier methods is permitted; interaction between atazanavir and oral contraceptives has not been studied.
- Subjects must be able to provide written informed consent;
Key exclusion criteria (20 listed)
- Prior use (=>3 days) of atazanavir, TVF or LPV/RTV; if history of SQV, then must be phenotypically sensitive
- the current failing antiretroviral regimen must have been administered for at least eight weeks at he initiation of screening and must not include both a PI and NNRTI
- Presence of a newly diagnosed HIV-related opportunistic infection or any medical requiring acute therapy at the time of enrollment
- Proven or suspected acute hepatitis in the 30 days prior to study entry. Subjects with chronic hepatitis are eligible provided that their liver function enzymes (ALT/AST) are <3 x ULN
- Previous therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatoxic, hepatoxic or cytotoxic potential within 3 months of study start or the expected need for such therapy at the time of enrollment of therapy with methadone or ribavirin/interferons or treatment with neurotoxic drugs or drugs that affect Cytochrome P450 3A4 (CYP3A4).
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 |
|---|---|---|
| Atazanavir + ritonavir + tenofovir + nucleosideAlso: BMS-232632, ReyatazActive Comparator, Capsules, tablets, Oral | Drug | I |
| Atazanavir + saquinavir + tenofovir + nucleosideAlso: BMS-232632, ReyatazActive Comparator, Capsules, tablets, Oral | Drug | II |
| Lopinavir/ritonavir + tenofovir + nucleosideActive Comparator, Capsules, tablets, Oral | Drug | III |
Primary outcome
Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24
Time frame: Baseline, Week 24
Mean Change From Baseline in HIV RNA at Week 48
Time frame: Baseline, Week 48
Mean Change From Baseline in HIV RNA at Week 96
Time frame: Baseline, Week 96
42 secondary outcomes
Mean Change From Baseline in HIV RNA at Week 2
Time frame: Baseline, Week 2
Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity)
Time frame: Baseline, Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity)
Time frame: Baseline, Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96
Time frame: Baseline, Week 96
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24
Time frame: Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24, by PI Sensitivity
Time frame: Baseline, Week 24
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48
Time frame: Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48, by PI Sensitivity
Time frame: Baseline, Week 48
Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96
Time frame: Week 96
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24
Time frame: Week 24
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48
Time frame: Week 48
Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96
Time frame: Week 96
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24
Time frame: Week 24
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48
Time frame: Week 48
Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96
Time frame: Week 96
Change From Baseline in CD4 Cell Count at Week 24
Time frame: Baseline, Week 24
Change From Baseline in CD4 Cell Count at Week 48
Time frame: Baseline, Week 48
Change From Baseline in CD4 Cell Count at Week 96
Time frame: Baseline, Week 96
Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 24
Time frame: Baseline, Week 24
Correlation of ATV Minimum Plasma Concentration (Cmin), Inhibitory Quotient (IQ), and Number of Protease Inhibitor (PI) Mutations at Baseline With HIV RNA Change From Baseline at Week 48
Time frame: Baseline, Week 48
Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 24
Time frame: Baseline, Week 24
Correlation of ATV Minimum Plasma Concentration (Cmin) Inhibitory Quotient (IQ), and Number of PI Mutations at Baseline and CD4 Cell Count Change From Baseline at Week 48
Time frame: Baseline, Week 48
Lipid Mean Percent Change From Baseline at Week 24
Time frame: Baseline, Week 24
Lipid Mean Percent Change From Baseline at Week 48
Time frame: Week 48
Lipid Mean Percent Change From Baseline at Week 96, Observed Values
Time frame: Week 96
Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48
Time frame: From Enrollment through Week 48
Most Common AEs and AEs of Interest Through Week 48
Time frame: From Enrollment to Week 48
Fasting Glucose Mean Change From Baseline at Week 24
Time frame: Baseline, Week 24
Fasting Glucose Mean Change From Baseline at Week 48
Time frame: Week 48
Grade 3/4 Laboratory Abnormalities Through Week 48
Time frame: From Enrollment to Week 48
Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point
Time frame: Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
PR Interval and Change From Baseline by Analysis Time Point
Time frame: Baseline, Week 4 predose, 2-3 hours postdose, 6-12 hours postdose, Week 12, Week 24, Week 48
Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire
Time frame: Baseline, Week 24, Week 48
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (Week 48)
Time frame: Baseline, Week 24, Week 48
Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Baseline, Mid-Study (Week 24), and Final (Week 48)
Time frame: Baseline, Week 24, Week 48
Number of Participants Utilizing Resources for Managing Lipid Elevation
Time frame: Baseline, Week 24, Week 48
Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values
Time frame: collected at the pre-dose time point after receiving atazanavir for at least four weeks
HIV IC50 at Week 24
Time frame: Week 24
Inhibitory Quotient at Week 24
Time frame: Baseline, Week 24
Inhibitory Quotient at Week 48
Time frame: Baseline, Week 48
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Dec 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atazanavir + ritonavir + tenofovir + nucleoside, Atazanavir + saquinavir + tenofovir + nucleoside and Lopinavir/ritonavir + tenofovir + nucleoside in people with HIV Infections, run by Bristol-Myers Squibb at 29 sites in United States.
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 13 inclusion and 20 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: finished, as of the sponsor's last update on 24 Dec 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24 (time frame: Baseline, Week 24). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Dec 2010.