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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01440569
• Other study ID #: GS-US-216-0130
• Secondary ID: 2011-003501-22
• Status: Completed
• Phase: Phase 3
• First received: September 22, 2011
• Last updated: November 20, 2015
• Start date: September 2011
• Est. completion date: October 2015

Study information

• Verified date: November 2015
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 extension period to receive cobicistat and attend visits every 12 weeks until it becomes commercially available, or until Gilead Sciences elects to terminate development of cobicistat.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 314
• Est. completion date: October 2015
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Immunologic Deficiency Syndromes

Intervention

Drug:
• COBI
Cobicistat (COBI) 150 mg tablet administered orally with food once daily
• DRV
Darunavir (DRV) 800 mg (2 x 400 mg tablets) administered orally with food once daily
• 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.

Locations

Country	Name	City	State
Puerto Rico	Clinical Research Puerto Rico	San Juan
United States	Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)	Annandale	Virginia
United States	Atlanta ID group	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	Community Research Initiative of New England	Boston	Massachusetts
United States	Carolinas Medical Center-Myer's Park Infectious Disease Clinic	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	Northstar Medical Center	Chicago	Illinois
United States	Southwest Infectious Disease Clinical Research, Inc.	Dallas	Texas
United States	Trinity Health and Wellness Center/AIDS Arms, Inc.	Dallas	Texas
United States	Infectious Disease Specialists of Atlanta	Decatur	Georgia
United States	Apex Research LLC	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Gary J. Richmond,M.D., P.A.	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Tarrant County Infectious Disease	Fort Worth	Texas
United States	Hawaii Center for AIDS, University of Hawaii	Honolulu	Hawaii
United States	Gordon Crofoot MD, PA	Houston	Texas
United States	Gordon E. Crofoot MD PA	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	Long Beach Education and Research Consultants, PC	Long Beach	California
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Anthony Mills MD Inc	Los Angeles	California
United States	Peter J Ruane MD Inc.	Los Angeles	California
United States	Johns Hopkins University	Lutherville	Maryland
United States	Mercer University	Macon	Georgia
United States	North Shore University Hospital / Division of Infectious Diseases	Manhasset	New York
United States	Wohlfeiler, Piperato and Associates, LLC	Miami Beach	Florida
United States	HIV Program Hennepin County Medical Center	Minneapolis	Minnesota
United States	Greiger Clinic	Mt. Vernon	New York
United States	Beth Israel Medical Center	New York	New York
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	Orlando Immunology Center	Orlando	Florida
United States	Stanford University	Palo Alto	California
United States	Philadelphia FIGHT	Philadelphia	Pennsylvania
United States	University of PA	Philadelphia	Pennsylvania
United States	Spectrum Medical Group	Phoenix	Arizona
United States	Miriam Hospital	Providence	Rhode Island
United States	Kaiser Permanente Medical Group	Sacramento	California
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	Metropolis Medical	San Francisco	California
United States	Swedish Medical Center	Seattle	Washington
United States	South Jersey Infectious Disease	Somers Point	New Jersey
United States	Central West Clinical Research Inc	St. Louis	Michigan
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	Dupont Circle Physician's Group	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia
United States	Wake Forest University Health Services	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Gilead Sciences	Janssen, LP

Countries where clinical trial is conducted

United States,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Onset of Any Treatment-emergent Grade 3 or 4 Adverse Event Between Baseline and Week 24		Up to 24 weeks	No
Secondary	Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 24 (Snapshot Analysis)		Week 24	No
Secondary	Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis)		Week 48	No
Secondary	Change From Baseline in CD4+ Cell Count at Week 24		Baseline; Week 24	No
Secondary	Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48	No
Secondary	Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 24		Up to 24 weeks	No
Secondary	Percentage of Participants Experiencing Any Treatment-emergent Adverse Event and Any Treatment-emergent Adverse Event Leading to Discontinuation of Study Drug Through Week 48		Up to 48 weeks	No