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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 24

Mean 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 2

Participants 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

Page last updated: August 23, 2015

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