Second-line Treatment of HIV-1 With Ritonavir Boosted Atazanavir or Darunavir With an Optimized NRTI Backbone

NCT01605084 | Withdrawn Phase 3

• 2 other identifiers: AI424-4932011-006186-18
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of this study is to determine the proportion of subjects with HIV-1 RNA \< 50 c/mL at Week 48 in patients who failed their first line therapy containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) or an integrase inhibitor

Conditions

HIV

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with Human immunodeficiency virus 1 (HIV-1) Ribonucleic Acid (RNA) < 50 c/mL

  At Week 48

Secondary Outcomes (5)

• Proportion of subjects with HIV-1 RNA < 50 c/mL

  At week 24

• Change from baseline in CD4 cell count

  Baseline (Week 0) and at week 48

• Incidence rates of serious adverse event (SAEs) and adverse events (AEs) leading to discontinuation

  up to week 48

• Incidence rates of antiretroviral resistance measured by newly emergent genotypic substitutions and phenotypic resistance to study drugs for virologic failure

  up to week 48

• Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 by baseline M184V presence or absence

  Week 48

Study Arms (2)

Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone

EXPERIMENTAL

Drug: Atazanavir; Drug: Ritonavir; Drug: Optimized NRTI backbone

Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone

EXPERIMENTAL

Drug: Darunavir; Drug: Ritonavir; Drug: Optimized NRTI backbone

Interventions

Atazanavir DRUG

Capsule, Oral, 300 mg, Once daily (QD), 48 weeks

Also known as: REYATAZ®

Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone

Darunavir DRUG

Oral, Two 400 mg Tablets, Once daily (QD), 48 weeks

Also known as: PREZISTA®

Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone

Ritonavir DRUG

Tablet, Oral, 100 mg, Once daily (QD), 48 weeks

Also known as: NORVIR®

Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone; Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone

Optimized NRTI backbone DRUG

tablet/capsule, Noninvestigational products i.e. NRTI backbone will be administered according to their respective package inserts for 48 weeks NRTI backbone are: \- Abacavir (300 mg), Tenofovir (300 mg), Didanosine (250 mg or 400 mg), Stavudine (30 mg or 40 mg), Emtricitabine (200 mg), Lamivudine (300 mg), Zidovudine (300 mg), EPZICOM® (600 mg Ziagen® + 300 mg Lamivudine), COMBIVIR® (150 mg Lamivudine + 300 mg Zidovudine) The following NRTI combinations are prohibited in this study: * Didanosine + Stavudine * Zidovudine + Stavudine * Lamivudine + Emtricitabine

Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone; Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone

Eligibility Criteria

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

You may qualify if:

• Signed informed consent.
• HIV-1 infected patients with viremia (VL ≥ 500/mL) on or after their first NNRTI or INI-based cART regimen and meeting one of the two criteria below:.
• i) On 1st line Non-nucleoside reverse transcriptase inhibitor (NNRTI) or Integrase inhibitor (INI)-based Combination antiretroviral therapy (cART) with HIV-1 RNA ≥ 500 c/ML after being on the same therapy for at least 12 weeks.
• ii) Off 1st line NNRTI or INI-based Combination antiretroviral therapy (cART) for at least 2 weeks after having been on antiviral therapy for at least 4 weeks and who are non-compliant and off first line cART without a history of virologic failure with resistance, with a : HIV-1 RNA ≥ 500 c/ML.
• Fully sensitive genotype and phenotype report for Atazanavir/Ritonavir (clinical cut-off of 5.2) and Darunavir/Ritonavir (clinical cut-off ranging from 10 to 90).
• At least one NRTI other than Lamivudine (3TC) or emtricitabine (FTC) with full sensitivity (one "active" NRTI) by genotype and phenotype, ie, PhenoSense Genotype (GT), report must provide a "sensitive" net assessment of susceptibility. An NRTI or PI (reported with or without ritonavir) with a "partially sensitive" net assessment will not be considered "fully sensitive".
• Mentally able to participate in the study.
• Men and women ≥ 18 years old.
• Women of child bearing potential who engage in vaginal intercourse and who are not clinically sterilized must use highly effective methods of birth control during the study.

You may not qualify if:

• i) Subjects with any darunavir associated mutations\* at baseline (\*V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V).
• ii) Subjects with a major mutation to Atazanavir sulfate consisting of N88S.
• iii) Subjects with more than 3 of any of the following Atazanavir sulfate related mutations:D30N, M36I/V, M46I/L/T, I54V/L/T/M/A, A71V/T/I/G, G73S/A/C/T, V77I, V82A/F/T/S/I, I84V/A, N88D or L90M.
• \- Subjects with \< 1 fully active NRTI on PhenoSense report, other than lamivudine and emtricitabine.
• Diagnosed with active tuberculosis.
• Chronic hepatitis B infection.
• Hepatitis C-positive patients who are not clinically stable or need treatment during the study period.
• Acute hepatitis in the 30 days prior to study entry.
• Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug.
• Intractable diarrhea within 30 days prior to study entry.
• Presence of a newly diagnosed Human immunodeficiency virus (HIV)-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment.
• Subject's with Cushing's syndrome.
• Untreated hypothyroidism or hyperthyroidism.
• Recent therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start.
• Subject's with obstructive liver disease.

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (14)

Southwest Center For Hiv/Aids

Phoenix, Arizona, 85006, United States

Location

Southwest Center For Hiv/Aids

Phoenix, Arizona, United States

Location

Health For Life Clinic Pllc

Little Rock, Arkansas, 72207, United States

Location

Anthony M. Mills Md Inc

Los Angeles, California, 90069, United States

Location

Uc Davis Medical Center

Sacramento, California, 95817, United States

Location

Metropolis Medical Pc

San Francisco, California, 94109, United States

Location

Indiana University Hospital

Indianapolis, Indiana, 46202, United States

Location

Be Well Medical Center

Berkley, Michigan, United States

Location

Southampton Health Center

St Louis, Missouri, 63139, United States

Location

Southampton Health Center

St Louis, Missouri, United States

Location

I.D. Care Associates

Hillsborough, New Jersey, 08844, United States

Location

Saint Michael'S Medical Center

Newark, New Jersey, 07102, United States

Location

James J Peters VAMC

The Bronx, New York, 10468, United States

Location

Infectious Disease Clinic & AI

The Bronx, New York, United States

Location

Related Links

• Investigator Inquiry form

MeSH Terms

Interventions

Atazanavir Sulfate; Darunavir; Ritonavir

Intervention Hierarchy (Ancestors)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oligopeptides; Peptides; Amino Acids, Peptides, and Proteins; Sulfonamides; Amides; Organic Chemicals; Carbamates; Acids, Acyclic; Carboxylic Acids; Sulfones; Sulfur Compounds; Furans; Thiazoles; Azoles

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 22, 2012
• First Posted: May 24, 2012
• Study Start: June 30, 2012
• Primary Completion: August 31, 2014
• Study Completion: August 31, 2014
• Last Updated: December 19, 2023

Record last verified: 2023-12

Locations

US (14)