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

Study Overview
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Brief Summary
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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 will be randomized in a 2:1 ratio to receive Stribild or Atripla. Randomization will be stratified by HIV-1 RNA level (≤ 100,000 copies/mL or > 100,000 copies/mL) at screening. After Week 48, participants will continue to take their blinded study drug and attend visits every 12 weeks until treatment assignments are unblinded (Week 60), at which point all participants will attend an Unblinding Visit and be 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).

Official Title
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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

Conditions
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HIV, HIV Infections

Intervention / Treatment
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* Drug: Stribild
* Drug: Atripla


Participation Criteria
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Eligibility Criteria
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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/µL 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 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Stribild<br> | Drug: Stribild<br>* 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)<br>|
| Active Comparator: Atripla<br> | Drug: Atripla<br>* Atripla (EFV 150 mg/FTC 200mg/TDF 300 mg) STR QHS + placebo to match Stribild QD<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) Less Than 50 Copies/mL at Week 24 | The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 24 was summarized. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Percentage of Participants With HIV-1 RNA Less Than 50 Copies/mL at Week 48 | The percentage of participants with plasma HIV-1 RNA < 50 copies/mL at Week 48 was summarized. | Week 48 | 
| Change From Baseline in HIV-1 RNA (log_10 Copies/mL) | Change = Week 24 or 48 value minus baseline value | Baseline to Weeks 24 and 48 | 
| Change From Baseline in Cluster Determinant 4 (CD4) Cell Count at Week 24 | Change = Week 24 value minus baseline value | Baseline to Week 24 | 
| Change From Baseline in CD4 Cell Count at Week 48 | Change = Week 48 value minus baseline value | Baseline to Week 48 | 
| 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 | 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. | Baseline to Weeks 24 and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, HIV-1, Antiretroviral Treatment-Naive, treatment naive