Study of the Safety and Efficacy of Stribild Versus Atripla in Human Immunodeficiency Virus, Type 1 (HIV-1) Infected, Antiretroviral Treatment-Naive Adults

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00869557
First received: March 24, 2009
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

The objective of this double-blinded, multicenter, randomized, active-controlled study is to evaluate the safety and efficacy of Stribild, a single-tablet regimen (STR) containing fixed doses of elvitegravir (EVG)/GS-9350 (cobicistat; COBI )/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/FTC/TDF (Atripla) in HIV-1 infected, antiretroviral treatment-naive adult participants. Stribild offers an alternative STR for patients who are not candidates for non-nucleoside reverse transcriptor (NNRTI)-based STRs.

Participants were randomized in a 2:1 ratio to receive Stribild or Atripla. Randomization was stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. After Week 48, participants continued to take their blinded study drug and attended visits every 12 weeks until treatment assignments were unblinded (Week 60), at which point all participants attended an Unblinding Visit and were given the option to participate in an open-label rollover extension (the extension is scheduled to be open until Stribild becomes commercially available, or until Gilead Sciences elects to terminate the study).


Condition Intervention Phase
HIV
HIV Infections
Drug: Stribild
Drug: Atripla
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Emtricitabine/Tenofovir Disoproxil Fumarate/GS-9350 Versus Atripla® (Efavirenz 600 mg/Emtricitabine 200 mg/Tenofovir Disoproxil Fumarate 300 mg) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 24 was summarized.


Secondary Outcome Measures:
  • The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 48 was summarized.

  • Change From Baseline in HIV-1 RNA (log_10 Copies/mL) [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
    Change = Week 24 or 48 value minus baseline value

  • Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Change = Week 24 value minus baseline value

  • Change From Baseline in CD4 Cell Count at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
    Change = Week 48 value minus baseline value

  • The Percentage of Participants With Virologic Success at Weeks 24 and 48 Using FDA-Defined Snapshot Analysis and HIV-1 RNA Less Than 50 Copies/mL [ Time Frame: Baseline to Weeks 24 and 48 ] [ Designated as safety issue: No ]
    The percentage of participants with virologic success at Weeks 24 and 48 assessed using the FDA-defined snapshot analysis for an HIV-1 RNA cutoff of 50 copies/mL was summarized.


Enrollment: 71
Study Start Date: April 2009
Study Completion Date: September 2013
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Stribild Drug: Stribild
Stribild (EVG 150 mg/COBI 150 mg/FTC 200 mg/TDF 300 mg) STR once daily (QD) + placebo to match Atripla once daily prior to bedtime (QHS)
Active Comparator: Atripla Drug: Atripla
Atripla (EFV 150 mg/FTC 200mg/TDF 300 mg) STR QHS + placebo to match Stribild QD

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Plasma HIV-1 RNA levels ≥ 5,000 copies/mL
  • No prior use of any approved or experimental anti-HIV drug
  • Normal electrocardiogram (ECG)
  • Adequate renal function: estimated glomerular filtration rate ≥ 80 mL/min according to the Cockcroft Gault formula
  • Hepatic transaminases ≤ 2.5 x upper limit of normal (ULN)
  • Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
  • Adequate hematologic function
  • Cluster determinant 4 (CD4) cell count > 50 cells/uL
  • Serum amylase ≤ 1.5 x ULN
  • Normal thyroid-stimulating hormone
  • Negative serum pregnancy test (for females of childbearing potential only)
  • Males and females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 12 weeks following the last dose of study drugs
  • Age ≥ 18 years
  • Life expectancy ≥ 1 year
  • Ability to understand and sign a written informed consent form

Exclusion Criteria:

  • New acquired immunodeficiency syndrome (AIDS) defining condition diagnosed within the 30 days prior to screening
  • Documented drug resistance to nucleoside reverse transcriptase inhibitors or nonnucleoside reverse transcriptase inhibitors or primary protease inhibitor resistance mutation(s)
  • Hepatitis B surface antigen positive
  • Hepatitis C antibody positive
  • Participants experiencing cirrhosis
  • Participants experiencing ascites
  • Participants experiencing encephalopathy
  • Females who are breastfeeding
  • Positive serum pregnancy test (for females of childbearing potential)
  • Vaccinated within 90 days of study dosing
  • History or family history of Long QT Syndrome or family history of sudden cardiac death or unexplained death in an otherwise healthy individual under the age of 30
  • Presence or history of cardiovascular disease, cardiomyopathy, and/or cardiac conduction abnormalities
  • Prolonged QTcF interval at screening
  • PR interval ≥ 200 msec or ≤ 120 msec on ECG at screening
  • QRS ≥ 120 msec on ECG at screening
  • Implanted defibrillator or pacemaker
  • Participants receiving ongoing therapy with any disallowed medications
  • Current alcohol or substance use judged to potentially interfere with participant study compliance
  • History of or ongoing malignancy (including untreated carcinoma in situ) other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
  • Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
  • Participation in any other clinical trial without prior approval
  • Medications contraindicated for use with EFV, EVG, COBI, FTC, or TDF
  • Any known allergies to the excipients of Atripla or Stribild tablets
  • Any other clinical condition or prior therapy that would make the participant unsuitable for the study or unable to comply with the dosing requirements
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00869557

  Show 30 Study Locations
Sponsors and Collaborators
Gilead Sciences
  More Information

Additional Information:
Publications:
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00869557     History of Changes
Other Study ID Numbers: GS-US-236-0104
Study First Received: March 24, 2009
Results First Received: September 20, 2012
Last Updated: February 24, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV
HIV-1
Antiretroviral Treatment-Naive
treatment naive

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir disoproxil
Tenofovir
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 23, 2014