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

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

Intervention: Atazanavir (Drug); Darunavir (Drug); Ritonavir (Drug); Optimized NRTI backbone (Drug)

Phase: Phase 3

Status: Withdrawn

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 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

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

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

Secondary outcome:

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

Change from baseline in CD4 cell count

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

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

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

Detailed description: Allocation: Randomization will be stratified

- ATV = Atazanavir

- DRV = Darunavir

- RTV = Ritonavir

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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

Locations and Contacts

Southwest Center For Hiv/Aids, Phoenix, Arizona 85006, United States

Health For Life Clinic Pllc, Little Rock, Arkansas 72207, United States

Uc Davis Medical Center, Sacramento, California 95817, United States

Metropolis Medical Pc, San Francisco, California 94109, United States

Indiana University Hospital, Indianapolis, Indiana 46202, United States

Be Well Medical Center, Berkley, Michigan 48072, United States

Southampton Health Center, St Louis, Missouri 63139, United States

I.D. Care Associates, Hillsborourgh, New Jersey 08844, United States

Saint Michael'S Medical Center, Newark, New Jersey 07102, United States

Infectious Disease Clinic & AI, Bronx, New York, United States

James J Peters VAMC, Bronx, New York 10468, United States

Additional Information

BMS Clinical Trials Disclosure

Investigator Inquiry form

For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm

Starting date: June 2012
Last updated: December 3, 2012

Page last updated: August 23, 2015

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