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

NCT01440569 | Completed Phase 3 Results

• 2 other identifiers: GS-US-216-01302011-003501-22
• Study Type: interventional
• Target: 314
• Locations: 2 countries
• Sites: 49

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.

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Keywords

HIV-1; HIV; Treatment Naïve; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Onset of Any Treatment-emergent Grade 3 or 4 Adverse Event Between Baseline and Week 24

  Up to 24 weeks

Secondary Outcomes (6)

• Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 24 (Snapshot Analysis)

  Week 24

• Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 (Snapshot Analysis)

  Week 48

• Change From Baseline in CD4+ Cell Count at Week 24

  Baseline; Week 24

• Change From Baseline in CD4+ Cell Count at Week 48

  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

  Up to 24 weeks

Study Arms (1)

COBI-boosted DRV

EXPERIMENTAL

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; Drug: DRV; Drug: NRTIs

Interventions

COBI DRUG

150 mg tablet administered orally with food once daily

Also known as: Tybost®, GS-9350

COBI-boosted DRV

DRV DRUG

800 mg (2 x 400 mg tablets) administered orally with food once daily

Also known as: Prezista®, TMC114

COBI-boosted DRV

NRTIs DRUG

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.

COBI-boosted DRV

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (49)

Spectrum Medical Group

Phoenix, Arizona, 85012, United States

Location

Long Beach Education and Research Consultants, PC

Long Beach, California, 90813, United States

Location

Peter J Ruane MD Inc.

Los Angeles, California, 90036, United States

Location

Anthony Mills MD Inc

Los Angeles, California, 90069, United States

Location

Stanford University

Palo Alto, California, 94304, United States

Location

Kaiser Permanente Medical Group

Sacramento, California, 95825, United States

Location

La Playa Medical Group and Clinical Research

San Diego, California, 92103, United States

Location

Metropolis Medical

San Francisco, California, 94109, United States

Location

Apex Research LLC

Denver, Colorado, 80220, United States

Location

Dupont Circle Physician's Group

Washington D.C., District of Columbia, 20009, United States

Location

Whitman-Walker Health

Washington D.C., District of Columbia, 20009, United States

Location

Gary J. Richmond,M.D., P.A.

Fort Lauderdale, Florida, 33316, United States

Location

Midway Immunology and Research Center

Ft. Pierce, Florida, 34983, United States

Location

Wohlfeiler, Piperato and Associates, LLC

Miami Beach, Florida, 33139, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

St. Joseph's Comprehensive Research Institute

Tampa, Florida, 33614, United States

Location

Atlanta ID group

Atlanta, Georgia, 30309, United States

Location

Infectious Disease Specialists of Atlanta

Decatur, Georgia, 30033, United States

Location

Mercer University

Macon, Georgia, 31220, United States

Location

Hawaii Center for AIDS, University of Hawaii

Honolulu, Hawaii, 96816, United States

Location

Howard Brown Health Center

Chicago, Illinois, 60613, United States

Location

Northstar Medical Center

Chicago, Illinois, 60657, United States

Location

Johns Hopkins University

Lutherville, Maryland, 21093, United States

Location

Community Research Initiative of New England

Boston, Massachusetts, 02215, United States

Location

Be Well Medical Center

Berkley, Michigan, 48072, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Central West Clinical Research Inc

Saint Louis, Michigan, 63108, United States

Location

HIV Program Hennepin County Medical Center

Minneapolis, Minnesota, 55415, United States

Location

Saint Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

South Jersey Infectious Disease

Somers Point, New Jersey, 08244, United States

Location

North Shore University Hospital / Division of Infectious Diseases

Manhasset, New York, 11030, United States

Location

Greiger Clinic

Mount Vernon, New York, 10550, United States

Location

Beth Israel Medical Center

New York, New York, 10003, United States

Location

Carolinas Medical Center-Myer's Park Infectious Disease Clinic

Charlotte, North Carolina, 28079, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Wake Forest University Health Services

Winston-Salem, North Carolina, 27157, United States

Location

University of PA

Philadelphia, Pennsylvania, 19104, United States

Location

Philadelphia FIGHT

Philadelphia, Pennsylvania, 19107, United States

Location

Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

Trinity Health and Wellness Center/AIDS Arms, Inc.

Dallas, Texas, 75208, United States

Location

Southwest Infectious Disease Clinical Research, Inc.

Dallas, Texas, 75219, United States

Location

Tarrant County Infectious Disease

Fort Worth, Texas, 76104, United States

Location

Therapeutic Concepts, PA

Houston, Texas, 77004, United States

Location

Gordon Crofoot MD, PA

Houston, Texas, 77098, United States

Location

DCOL Center for Clinical Research

Longview, Texas, 75605, United States

Location

Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)

Annandale, Virginia, 22003, United States

Location

Swedish Medical Center

Seattle, Washington, 89104, United States

Location

Clinical Research Puerto Rico

San Juan, 00909, Puerto Rico

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome; HIV Infections

Interventions

Cobicistat; Darunavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Carbamates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Sulfonamides; Amides; Sulfones; Furans

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences, Inc.

ClinicalTrialDisclosures@gilead.com

Study Officials

• Marshall Fordyce, MD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2011
• First Posted: September 26, 2011
• Study Start: September 1, 2011
• Primary Completion: August 1, 2012
• Study Completion: October 1, 2015
• Last Updated: December 14, 2016
• Results First Posted: October 28, 2014

Record last verified: 2016-10

Locations

US (48); PR (1)