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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT01605084
First received: May 22, 2012
Last updated: December 3, 2012
Last verified: December 2012
  Purpose

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


Condition Intervention Phase
HIV
Drug: Atazanavir
Drug: Darunavir
Drug: Ritonavir
Drug: Optimized NRTI backbone
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Phase 3B Study in HIV-Infected Individuals With Viremia on or After Their First-Line Non-Nucleoside Reverse Transcriptase Inhibitor or Integrase Inhibitor-Based Regimen and Starting a Second-Line Regimen Consisting of ATV/RTV or DRV/RTV With an Optimized NRTI Backbone

Resource links provided by NLM:


Further study details as provided by Bristol-Myers Squibb:

Primary Outcome Measures:
  • Proportion of subjects with Human immunodeficiency virus 1 (HIV-1) Ribonucleic Acid (RNA) < 50 c/mL [ Time Frame: At Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects with HIV-1 RNA < 50 c/mL [ Time Frame: At week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4 cell count [ Time Frame: Baseline (Week 0) and at week 48 ] [ Designated as safety issue: No ]
  • Incidence rates of serious adverse event (SAEs) and adverse events (AEs) leading to discontinuation [ Time Frame: up to week 48 ] [ Designated as safety issue: Yes ]
  • Incidence rates of antiretroviral resistance measured by newly emergent genotypic substitutions and phenotypic resistance to study drugs for virologic failure [ Time Frame: up to week 48 ] [ Designated as safety issue: Yes ]
  • Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 by baseline M184V presence or absence [ Time Frame: Week 48 ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: June 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone Drug: Atazanavir
Capsule, Oral, 300 mg, Once daily (QD), 48 weeks
Other Name: REYATAZ®
Drug: Ritonavir
Tablet, Oral, 100 mg, Once daily (QD), 48 weeks
Other Name: NORVIR®
Drug: Optimized NRTI backbone

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
Experimental: Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone Drug: Darunavir
Oral, Two 400 mg Tablets, Once daily (QD), 48 weeks
Other Name: PREZISTA®
Drug: Ritonavir
Tablet, Oral, 100 mg, Once daily (QD), 48 weeks
Other Name: NORVIR®
Drug: Optimized NRTI backbone

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

Detailed Description:

Allocation: Randomization will be stratified

  • ATV = Atazanavir
  • DRV = Darunavir
  • RTV = Ritonavir
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Signed informed consent
  2. 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:

    • 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
    • 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
  3. 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)
  4. 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"

4. Mentally able to participate in the study 5. 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

Exclusion Criteria:

  1. Screening HIV genotype showing presence at baseline of any of the following Protease inhibitor (PI) Mutation Patterns associated with genotypic resistance to Atazanavir sulfate/ Ritonavir or Darunavir/Ritonavir will lead to exclusion:

    1. Subjects with any darunavir associated mutations* at baseline (*V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V)
    2. Subjects with a major mutation to Atazanavir sulfate consisting of N88S
    3. 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
  2. Subjects with < 1 fully active NRTI on PhenoSense report, other than lamivudine and emtricitabine
  3. Diagnosed with active tuberculosis
  4. Chronic hepatitis B infection
  5. Hepatitis C-positive patients who are not clinically stable or need treatment during the study period
  6. Acute hepatitis in the 30 days prior to study entry
  7. Any gastrointestinal disease or surgical procedure that may impact the absorption of study drug
  8. Intractable diarrhea within 30 days prior to study entry
  9. Presence of a newly diagnosed Human immunodeficiency virus (HIV)-related opportunistic infection or any medical condition requiring acute therapy at the time of enrollment
  10. Subject's with Cushing's syndrome
  11. Untreated hypothyroidism or hyperthyroidism
  12. Recent therapy with agents with significant systemic myelosuppressive, neurotoxic, pancreatotoxic, hepatotoxic or cytotoxic potential within 3 months of study start
  13. Subject's with obstructive liver disease
  14. Active alcohol or illegal substance use
  15. Inability to swallow capsules
  16. Active peripheral neuropathy
  17. Presence of cardiomypathy or any significant cardiovascular disease
  18. Known, clinically significant cardiac conduction system disease
  19. Physical and Laboratory Test Findings:

    • Moderate to severe hepatic insufficiency
    • Screening laboratory values as follows:

      • T4 < 4mcg/dL or >11mcg/dL and/or Thyroid-stimulating hormone (TSH) <0.5mU/L or >5.0mU/L
      • Calculated creatinine clearance < 60 cc/min
      • Hemoglobin < 8.0 g/dL
      • Total serum lipase ≥ 1.4 times the upper limit of normal (ULN)
      • Liver enzymes [Aspartate transaminase (AST), Alanine transaminase (ALT)] ≥ 5 times the ULN
      • Alkaline phosphatase > 5 times the ULN
      • Platelets < 50,000 cells/mm3
      • Positive blood screen for hepatitis B surface antigen (HBsAg)
      • Total serum bilirubin ≥ 1.5 times the ULN
  20. Allergies and Adverse Drug Reaction:

    • Previously demonstrated hypersensitivity to any of the components of atazanavir or the other experimental agents in this study
    • Darunavir contains a sulfonamide moiety. Darunavir should be used with caution in patients with a known sulfonamide allergy
    • History of allergy to atazanavir, ritonavir, or darunavir
    • History of allergy to NRTIs included as NRTI backbone options in this study
    • History of clinically relevant severe drug reaction
  21. Sex and Reproductive Status:

    • Women with a positive pregnancy test on enrollment prior to study drug administration
    • Women who become pregnant during the study will be taken off-protocol
    • Women using a prohibited contraceptive method
    • Women who are breastfeeding
  22. Other Exclusion Criteria

    • Prisoners or subjects who are involuntarily incarcerated
    • Subjects who are compulsorily detained for treatment of wither a psychiatric or physical illness
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01605084

Locations
United States, Arizona
Southwest Center For Hiv/Aids
Phoenix, Arizona, United States, 85006
United States, Arkansas
Health For Life Clinic Pllc
Little Rock, Arkansas, United States, 72207
United States, California
Uc Davis Medical Center
Sacramento, California, United States, 95817
Metropolis Medical Pc
San Francisco, California, United States, 94109
United States, Indiana
Indiana University Hospital
Indianapolis, Indiana, United States, 46202
United States, Michigan
Be Well Medical Center
Berkley, Michigan, United States, 48072
United States, Missouri
Southampton Health Center
St Louis, Missouri, United States, 63139
United States, New Jersey
I.D. Care Associates
Hillsborourgh, New Jersey, United States, 08844
Saint Michael'S Medical Center
Newark, New Jersey, United States, 07102
United States, New York
Infectious Disease Clinic & AI
Bronx, New York, United States
James J Peters VAMC
Bronx, New York, United States, 10468
Sponsors and Collaborators
Bristol-Myers Squibb
Investigators
Study Director: Bristol-Myers Squibb Bristol-Myers Squibb
  More Information

Additional Information:
No publications provided

Responsible Party: Bristol-Myers Squibb
ClinicalTrials.gov Identifier: NCT01605084     History of Changes
Other Study ID Numbers: AI424-493, 2011-006186-18
Study First Received: May 22, 2012
Last Updated: December 3, 2012
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
European Union: European Medicines Agency

Additional relevant MeSH terms:
Reverse Transcriptase Inhibitors
Ritonavir
Atazanavir
Darunavir
Integrase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
HIV Protease Inhibitors
Protease Inhibitors
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 15, 2014