HIVPhase 3SUPPRESSNCT01605084
Second-line Treatment of HIV-1 With Ritonavir Boosted Atazanavir or Darunavir With an Optimized NRTI Backbone
A Phase 3 study testing Atazanavir, Darunavir and Ritonavir in people with HIV, run by Bristol-Myers Squibb at 14 sites in United States.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- HIV
- What is being tested?
- Atazanavir, Darunavir and Ritonavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 14 sitesUnited States
- Study dates
- 30 Jun 2012to 31 Aug 2014
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:.
- 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.
- 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".
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- 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.
Who cannot join
- 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:.
- Subjects with any darunavir associated mutations* at baseline (*V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V).
- Subjects with a major mutation to Atazanavir sulfate consisting of N88S.
- 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.
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- 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.
- Active alcohol or illegal substance use.
- Inability to swallow capsules.
- Active peripheral neuropathy.
- Presence of cardiomypathy or any significant cardiovascular disease.
- Known, clinically significant cardiac conduction system disease.
- 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.
- 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.
- 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.
- Other Exclusion Criteria.
- Prisoners or subjects who are involuntarily incarcerated.
- Subjects who are compulsorily detained for treatment of wither a psychiatric or physical illness.
- Other protocol-defined Inclusion/Exclusion criteria apply.
Trial locations and contacts
14 sites in 1 country.
14 sites in 1 country
United States14 sites
Be Well Medical Center
Berkley, Michigan
I.D. Care Associates
Hillsborough, New Jersey, 08844
Indiana University Hospital
Indianapolis, Indiana, 46202
Health For Life Clinic Pllc
Little Rock, Arkansas, 72207
Anthony M. Mills Md Inc
Los Angeles, California, 90069
Saint Michael'S Medical Center
Newark, New Jersey, 07102
Southwest Center For Hiv/Aids
Phoenix, Arizona, 85006
Southwest Center For Hiv/Aids
Phoenix, Arizona
Uc Davis Medical Center
Sacramento, California, 95817
Metropolis Medical Pc
San Francisco, California, 94109
Southampton Health Center
St Louis, Missouri, 63139
Southampton Health Center
St Louis, Missouri
James J Peters VAMC
The Bronx, New York, 10468
Infectious Disease Clinic & AI
The Bronx, New York
About this study
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
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
Read the detailed description
Allocation: Randomization will be stratified
- ATV = Atazanavir
- DRV = Darunavir
- RTV = Ritonavir
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtazanavirDrug
Also called REYATAZ®
Capsule, Oral, 300 mg, Once daily (QD), 48 weeks
DarunavirDrug
Also called PREZISTA®
Oral, Two 400 mg Tablets, Once daily (QD), 48 weeks
RitonavirDrug
Also called NORVIR®
Tablet, Oral, 100 mg, Once daily (QD), 48 weeks
Optimized NRTI backboneDrug
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
| Study group | Role | What they receive |
|---|---|---|
| Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone | Experimental | Not described Receives: Drug: Atazanavir; Drug: Ritonavir; Drug: Optimized NRTI backbone |
| Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone | Experimental | Not described Receives: Drug: Darunavir; Drug: Ritonavir; Drug: Optimized NRTI backbone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of subjects with Human immunodeficiency virus 1 (HIV-1) Ribonucleic Acid (RNA) < 50 c/mL
Measured: At Week 48
Secondary outcomes (5)
Proportion of subjects with HIV-1 RNA < 50 c/mL
Measured: At week 24
Change from baseline in CD4 cell count
Measured: Baseline (Week 0) and at week 48
Incidence rates of serious adverse event (SAEs) and adverse events (AEs) leading to discontinuation
Measured: up to week 48
Incidence rates of antiretroviral resistance measured by newly emergent genotypic substitutions and phenotypic resistance to study drugs for virologic failure
Measured: up to week 48
Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 by baseline M184V presence or absence
Measured: Week 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2012 (estimated)
- Study start30 Jun 2012
- Primary completion31 Aug 2014 (estimated)
- Study completion31 Aug 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HIVStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01605084
- Sponsor's protocol ID
- AI424-493
- Other IDs
- 2011-006186-18
- Acronym
- SUPPRESS
- Status last verified
- Dec 2023
- First submitted
- 22 May 2012
- Last updated
- 19 Dec 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01605084
- Acronym / sponsor ID
- SUPPRESS / AI424-493
- Conditions
- HIV
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Withdrawn
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- 30 Jun 2012 (actual)
- Primary completion
- 31 Aug 2014 (estimated)
- Study completion
- 31 Aug 2014 (estimated)
- First posted
- 24 May 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
Allocation: Randomization will be stratified
- ATV = Atazanavir
- DRV = Darunavir
- RTV = Ritonavir
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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:.
- 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".
Key exclusion criteria (48 listed)
- 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:.
- Subjects with any darunavir associated mutations* at baseline (*V11I, V32I, L33F, I47V, I50V, I54L, I54M, T74P, L76V, I84V and L89V).
- Subjects with a major mutation to Atazanavir sulfate consisting of N88S.
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AtazanavirAlso: REYATAZ®Capsule, Oral, 300 mg, Once daily (QD), 48 weeks | Drug | Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone |
| DarunavirAlso: PREZISTA®Oral, Two 400 mg Tablets, Once daily (QD), 48 weeks | Drug | Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone |
| RitonavirAlso: NORVIR®Tablet, Oral, 100 mg, Once daily (QD), 48 weeks | Drug | Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone, Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone |
| Optimized NRTI backbonetablet/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 | Drug | Arm 1: ATV/RTV 300/100 mg QD + optimized NRTI backbone, Arm 2: DRV/RTV 800/100 mg QD + optimized NRTI backbone |
Primary outcome
Proportion of subjects with Human immunodeficiency virus 1 (HIV-1) Ribonucleic Acid (RNA) < 50 c/mL
Time frame: At Week 48
5 secondary outcomes
Proportion of subjects with HIV-1 RNA < 50 c/mL
Time frame: At week 24
Change from baseline in CD4 cell count
Time frame: Baseline (Week 0) and at week 48
Incidence rates of serious adverse event (SAEs) and adverse events (AEs) leading to discontinuation
Time frame: up to week 48
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
Proportion of subjects with HIV-1 RNA < 50 c/mL at Week 48 by baseline M184V presence or absence
Time frame: Week 48
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Dec 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
14 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atazanavir, Darunavir and Ritonavir in people with HIV, run by Bristol-Myers Squibb at 14 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 48 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 19 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of subjects with Human immunodeficiency virus 1 (HIV-1) Ribonucleic Acid (RNA) < 50 c/mL (time frame: At Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Dec 2023.