Atazanavir (BMS-232632) in Combination With Ritonavir or Saquinavir, and Lopinavir/Ritonavir, Each With Tenofovir and a Nucleoside in Subjects With HIV

NCT00035932 | Completed Phase 3 Results

• 1 other identifier: AI424-045
• Study Type: interventional
• Target: 571
• Locations: 1 country
• Sites: 29

Brief 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.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (3)

• Mean Change From Baseline in HIV Ribonucleic Acid (RNA) at Week 24

  Baseline, Week 24

• Mean Change From Baseline in HIV RNA at Week 48

  Baseline, Week 48

• Mean Change From Baseline in HIV RNA at Week 96

  Baseline, Week 96

Secondary Outcomes (42)

• Mean Change From Baseline in HIV RNA at Week 2

  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)

  Baseline, Week 24

• Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 48, (Overall and by PI Sensitivity)

  Baseline, Week 48

• Participants Achieving Virologic Half Log Suppression (LOQ = 400 c/mL) at Week 96

  Baseline, Week 96

• Participants Achieving Virologic Half Log Suppression (LOQ = 50 c/mL) at Week 24

  Week 24

Study Arms (3)

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

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

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

Drug: Lopinavir/ritonavir + tenofovir + nucleoside

Interventions

Atazanavir + ritonavir + tenofovir + nucleoside DRUG

Active Comparator, Capsules, tablets, Oral

Also known as: BMS-232632, Reyataz

I

Atazanavir + saquinavir + tenofovir + nucleoside DRUG

Active Comparator, Capsules, tablets, Oral

Also known as: BMS-232632, Reyataz

II

Lopinavir/ritonavir + tenofovir + nucleoside DRUG

Active Comparator, Capsules, tablets, Oral

III

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (29)

Unknown Facility

San Francisco, California, 94121, United States

Location

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Torrance, California, 90502, United States

Location

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Boulder, Colorado, 80304, United States

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Altamonte Springs, Florida, United States

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Fort Lauderdale, Florida, 33306, United States

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Fort Lauderdale, Florida, 33308, United States

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Miami Beach, Florida, 33160, United States

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Orlando, Florida, 32801, United States

Location

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Decatur, Georgia, United States

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Honolulu, Hawaii, 96816, United States

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Boise, Indiana, United States

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Wichita, Kansas, 67214, United States

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Louisville, Kentucky, 40202, United States

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New Orleans, Louisiana, United States

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Brookline, Massachusetts, United States

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Fall River, Massachusetts, 02720, United States

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East Orange, New Jersey, United States

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Newark, New Jersey, 07103, United States

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Buffalo, New York, 14215, United States

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Manhasset, New York, 11030, United States

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New York, New York, 10019, United States

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Rochester, New York, 14620, United States

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Huntersville, North Carolina, 28078, United States

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Winston-Salem, North Carolina, 27157, United States

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Winston-Salem, North Carolina, 29203, United States

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Akron, Ohio, United States

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Dallas, Texas, 75246, United States

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Unknown Facility

Dallas, Texas, United States

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Unknown Facility

Houston, Texas, 77006, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Atazanavir Sulfate; Ritonavir; Tenofovir; Nucleosides; Saquinavir; Lopinavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Organophosphonates; Organophosphorus Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Glycosides; Carbohydrates; Nucleic Acids, Nucleotides, and Nucleosides; Isoquinolines; Quinolines; Pyrimidinones; Pyrimidines

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 6, 2002
• First Posted: May 8, 2002
• Study Start: November 1, 2001
• Primary Completion: July 1, 2003
• Study Completion: March 1, 2009
• Last Updated: December 24, 2010
• Results First Posted: December 24, 2010

Record last verified: 2010-11

Locations

US (29)