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

• ClinicalTrials.gov Identifier: NCT01440569
• Recruitment Status: Completed
• First Posted: September 26, 2011
• Results First Posted: October 28, 2014
• Last Update Posted: December 14, 2016
• Sponsor: Gilead Sciences
• Collaborator: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: September 22, 2011
• First Posted Date: September 26, 2011
• Results First Submitted Date: October 23, 2014
• Results First Posted Date: October 28, 2014
• Last Update Posted Date: December 14, 2016
• Study Start Date: September 2011
• Actual Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: October 23, 2014): 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 ]

Original Primary Outcome Measures (submitted: September 23, 2011)

The primary safety endpoint is the onset of any treatment emergent Grade 3 or Grade 4 adverse events [ Time Frame: 24 Weeks ]

Onset of any treatment emergent Grade 3 or Grade 4 adverse event through 24 weeks.

Current Secondary Outcome Measures (submitted: October 23, 2014)

• Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 24 (Snapshot Analysis) [ Time Frame: Week 24 ]
• Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis) [ Time Frame: Week 48 ]
• Change From Baseline in CD4+ Cell Count at Week 24 [ Time Frame: Baseline; Week 24 ]
• Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
• 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 ]
• 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 ]

Original Secondary Outcome Measures (submitted: September 23, 2011)

• The proportion of subjects achieving HIV 1 RNA < 50 copies/mL [ Time Frame: 24 & 48 Weeks ]
  The proportion of subjects achieving HIV 1 RNA < 50 copies/mL at Weeks 24 and 48.
• The change from baseline in CD4+ cell count [ Time Frame: 24 & 48 Weeks ]
  The change from baseline in CD4+ cell count at Weeks 24 and 48.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of Cobicistat-boosted Darunavir in HIV Infected Adults
• 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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Acquired Immunodeficiency Syndrome
• HIV Infections

Intervention

• 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.

Study Arms

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.

Interventions:

• Drug: COBI
• Drug: DRV
• Drug: NRTIs

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 23, 2014): 314
• Original Estimated Enrollment (submitted: September 23, 2011): 300
• Actual Study Completion Date: October 2015
• Actual Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, United States
• Removed Location Countries: Belgium, France, Germany

Administrative Information

• NCT Number: NCT01440569
• Other Study ID Numbers: GS-US-216-0130; 2011-003501-22 ( EudraCT Number )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Janssen Research & Development, LLC

Investigators

• Study Director: Marshall Fordyce, MD; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: October 2016