Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV
Information source: Bristol-Myers Squibb
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Atazanavir + ritonavir + tenofovir + nucleoside (Drug); Atazanavir + saquinavir + tenofovir + nucleoside (Drug); Lopinavir/ritonavir + tenofovir + nucleoside (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: Bristol-Myers Squibb Official(s) and/or principal investigator(s): Bristol-Myers Squibb, Study Director, Affiliation: Bristol-Myers Squibb
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). There
is a comparison arm with lopinavir (LPV)/RTV and TDF and a nucleoside.
Clinical Details
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
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24Mean Change From Baseline in HIV RNA at Week 48 Mean Change From Baseline in HIV RNA at Week 96
Secondary outcome: Mean Change From Baseline in HIV RNA at Week 2Participants Achieving Virologic Half Log Suppression (Limit of Quantification [LOQ] = 400 c/mL) at Week 24 (Overall and by Protease Inhibitor [PI] Sensitivity) Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity) Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96 Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24 Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24, by PI Sensitivity Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48 Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 48, by PI Sensitivity Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 96 Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 24 Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 48 Participants Achieving Treatment Response (LOQ = 400 c/mL) Without Prior Failure at Week 96 Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 24 Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 48 Participants Achieving Treatment Response (LOQ = 50 c/mL) Without Prior Failure at Week 96 Change From Baseline in CD4 Cell Count at Week 24 Change From Baseline in CD4 Cell Count at Week 48 Change From Baseline in CD4 Cell Count at 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 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 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 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 Lipid Mean Percent Change From Baseline at Week 24 Lipid Mean Percent Change From Baseline at Week 48 Lipid Mean Percent Change From Baseline at Week 96, Observed Values Deaths, Serious Adverse Events (SAEs), and Adverse Events (AEs) Through Week 48 Most Common AEs and AEs of Interest Through Week 48 Fasting Glucose Mean Change From Baseline at Week 24 Fasting Glucose Mean Change From Baseline at Week 48 Grade 3/4 Laboratory Abnormalities Through Week 48 Fridericia-corrected QT (QTcF) Interval and Change From Baseline by Analysis Time Point PR Interval and Change From Baseline by Analysis Time Point Adherence to Regimen Though Week 48 Based on MACS the Multicenter AIDS Cohort Study (MACS) Adherence Questionnaire Mean Score of European Quality of Life-5 Dimensions (EQ-5D) Health Index Score at Baseline, Mid-Study (Week 24), and Final (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) Number of Participants Utilizing Resources for Managing Lipid Elevation Mean ATV, RTV and SQV Minimum Concentration (Cmin) Values HIV IC50 at Week 24 Inhibitory Quotient at Week 24 Inhibitory Quotient at Week 48 HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 24 HIV RNA Level - Treated Subjects With Evaluable Cmins at Week 48
Eligibility
Minimum age: 16 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- 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):
1. 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
2. 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.
- 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:
1. serum creatine <1. 5 times the upper limit of normal (ULN)
2. total serum lipase <1. 4 times the ULN
3. liver enzymes alanine aminotransferase (AST), aspartate aminotransferase (ALT)
<3 times the ULN
4. total serum bilirubin <1. 5 times the ULN
Exclusion Criteria:
- 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
- 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:
1. Heart rate-corrected QT (QTc) interval >450 msec on the screening
electrocardiogram (EKG)
2. Heart rate <40 beats per minute (bpm)
3. Pause length >3 seconds seen on EKG
4. Clinical symptoms potentially related to heart block
5. 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.
Locations and Contacts
San Francisco, California 94121, United States
Torrance, California 90502, United States
Boulder, Colorado 80304, United States
Altamonte Springs, Florida, United States
Ft Lauderdale, Florida 33306, United States
Ft Lauderdale, Florida 33308, United States
Miami Beach, Florida 33160, United States
Orlando, Florida 32801, United States
Decatur, Georgia, United States
Honolulu, Hawaii 96816, United States
Boise, Indiana, United States
Wichita, Kansas 67214, United States
Louisville, Kentucky 40202, United States
New Orleans, Louisiana, United States
Brookline, Massachusetts, United States
Fall River, Massachusetts 02720, United States
East Orange, New Jersey, United States
Newark, New Jersey 07103, United States
Buffalo, New York 14215, United States
Manhasset, New York 11030, United States
New York, New York 10019, United States
Rochester, New York 14620, United States
Huntersville, North Carolina 28078, United States
Winston Salem, North Carolina 29203, United States
Winston-Salem, North Carolina 27157, United States
Akron, Ohio, United States
Dallas, Texas 75246, United States
Dallas, Texas, United States
Houston, Texas 77006, United States
Additional Information
BMS Clinical Trials Disclosure For FDA Safety Alerts and Recalls refer to the following link www.fda.gov/MEDWATCH/safety.htm
Starting date: November 2001
Last updated: November 29, 2010
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