Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults

Study Description

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Brief Summary:

This study is to evaluate the safety and tolerability of cobicistat-boosted darunavir plus two fully active nucleoside analogue reverse transcriptase inhibitors in HIV 1 infected, antiretroviral treatment-naive and treatment-experienced adults with no darunavir (DRV) resistance-associated mutations.

After the Week 48 Visit, participants will be given the option to participate in an open-label rollover phase to receive cobicistat and attend visits every 12 weeks until it becomes commercially available, or until Gilead Sciences elects to terminate development of cobicistat.

Condition or disease	Intervention/treatment	Phase
Acquired Immunodeficiency Syndrome; HIV Infections	Drug: COBI; Drug: DRV; Drug: NRTIs	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	314 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 3b, Open-Label, Single Arm Study to Evaluate the Safety and Efficacy of Cobicistat-boosted Darunavir Plus Two Fully Active Nucleoside Reverse Transcriptase Inhibitors in HIV-1 Infected, Antiretroviral Treatment-Naïve and -Experienced Adults With No Darunavir Resistance-associated Mutations
Study Start Date :	September 2011
Actual Primary Completion Date :	August 2012
Actual Study Completion Date :	October 2015

Arms and Interventions

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Arm

Intervention/treatment

Experimental: COBI-boosted DRV; Participants will receive DRV+COBI+2 investigator-selected NRTIs for 48 weeks, and may continue their regimen in the open-label rollover phase.

Drug: COBI; 150 mg tablet administered orally with food once daily; Other Names: Tybost®; GS-9350 Drug: DRV; 800 mg (2 x 400 mg tablets) administered orally with food once daily; Other Names: Prezista®; TMC114 Drug: NRTIs; Participants will receive 2 nucleoside analogue reverse transcriptase inhibitors (NRTIs) selected by the investigator after resistance testing at screening and administered according to prescribing information. NRTIs may include emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF), zidovudine+FTC/TDF, abacavir (ABC)+TDF, ABC+FTC/TDF, ABC+lamivudine (3TC), or didanosine (DDI)+FTC.

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With Onset of Any Treatment-emergent Grade 3 or 4 Adverse Event Between Baseline and Week 24 [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :

1. Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 24 (Snapshot Analysis) [ Time Frame: Week 24 ]
2. Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis) [ Time Frame: Week 48 ]
3. Change From Baseline in CD4+ Cell Count at Week 24 [ Time Frame: Baseline; Week 24 ]
4. Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
5. Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 24 [ Time Frame: Up to 24 weeks ]
6. Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 48 [ Time Frame: Up to 48 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Adult ≥ 18 years males or non-pregnant females
• Ability to understand and sign a written informed consent form
• General medical condition that does not interfere with the assessments and the completion of the trial
• Treatment Naive: No prior use of any approved or investigational antiretroviral drug for any length of time OR
• Treatment Experienced: Stable antiretroviral regimen for at least 12 weeks prior to screening
• Plasma HIV-1 RNA levels ≥ 1000 copies/mL at Screening
• Screening genotype report shows full sensitivity to two nucleoside analogue reverse transcriptase inhibitors (NRTIs) and no darunavir resistance-associated mutations
• Normal electrocardiogram (ECG)
• Hepatic transaminases ≤ 2.5 × upper limit of normal (ULN)
• Total bilirubin ≤ 1.5 mg/dL
• Adequate hematologic function
• Serum amylase ≤ 2 × ULN and serum lipase ≤ 3 × ULN
• Adequate renal function: Estimated glomerular filtration rate ≥ 80 mL/min
• Females of childbearing potential must agree to utilize protocol-recommended methods of contraception, or be nonheterosexually active, practice sexual abstinence or have a vasectomized partner from Screening throughout the duration of the study period and for 30 days following the last dose of study drug.
• Male subjects must agree to utilize protocol-recommended methods of contraception during heterosexual intercourse from the Screening visit, throughout the duration of the study and for 30 days following discontinuation of investigational medicinal product or be nonheterosexually active, practice sexual abstinence, or be vasectomized.

Exclusion Criteria:

• Previous or current use of darunavir
• A new AIDS-defining condition diagnosed within the 30 days prior to Screening
• Females who are breastfeeding
• Positive serum pregnancy test (if female of childbearing potential)
• Proven or suspected acute hepatitis in the 30 days prior to study entry
• Subjects receiving drug treatment for hepatitis C virus (HCV), or subjects who are anticipated to receive treatment for HCV during the course of the study
• Have a history of ongoing active liver disease or experiencing decompensated cirrhosis irrespective of liver enzyme levels
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance use that may interfere with subject study compliance
• A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma
• Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
• Participation in any other clinical trial
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements.
• Subjects receiving ongoing therapy with any of the medications, including drugs not to be used with cobicistat, darunavir, or investigator selected NRTIs; or subjects with any known allergies to cobicistat tablets, darunavir tablets or contraindications for the 2 NRTIs as part of the regimen.

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

  Show 49 Study Locations

Sponsors and Collaborators

Gilead Sciences

Janssen Research & Development, LLC

Investigators

Study Director:	Marshall Fordyce, MD	Gilead Sciences

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01440569 History of Changes
Other Study ID Numbers:	GS-US-216-0130; 2011-003501-22 ( EudraCT Number )
First Posted:	September 26, 2011
Results First Posted:	October 28, 2014
Last Update Posted:	December 14, 2016
Last Verified:	October 2016

Keywords provided by Gilead Sciences:

HIV-1; HIV; Treatment Naïve; Treatment Experienced

Additional relevant MeSH terms:

HIV Infections; Immunologic Deficiency Syndromes; Acquired Immunodeficiency Syndrome; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immune System Diseases; Slow Virus Diseases; Darunavir; Cobicistat	Reverse Transcriptase Inhibitors; HIV Protease Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors