Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Elvitegravir Versus Raltegravir
Condition: HIV Infection
MeSH terms: HIV Infections
Intervention: Elvitegravir; Raltegravir; EVG placebo; RAL placebo; Background regimen
Intervention description: Elvitegravir (EVG) tablet administered orally once daily with food; Raltegravir tablet administered orally twice daily according to prescribing information; Placebo to match elvitegravir administered orally once daily; RAL placebo administered orally twice daily.; Background Regimen (administered according to prescribing information) contains 1 fully-active ritonavir-boosted protease inhibitor (PI/r) plus 1 or 2 additional agents. The ritonavir-boosted PIs include either ATV, darunavir, fosamprenavir, LPV (Kaletra®), or tipranavir; the additional agents include abacavir (ABC), Combivir® (lamivudine (LAM)/zidovudine (ZDV) coformulated), didanosine, emtricitabine (FTC), enfuvirtide, Epzicom® (ABC/LAM coformulated), etravirine, LAM, maraviroc, tenofovir disoproxil fumarate (TDF), Truvada®, (FTC/TDF coformulated), and/or ZDV.
Intervention MeSH terms: Raltegravir Potassium; Elvitegravir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 724.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: HIV; HIV I; Treatment Experienced

Summary:

      The purpose of this study is to compare the safety, tolerability and efficacy of a regimen
      containing once-daily elvitegravir (EVG) versus twice-daily raltegravir (RAL) added to a
      background regimen (1 fully-active ritonavir (RTV)-boosted protease inhibitor (PI) plus 1 or
      2 additional antiretroviral (ARV) agents) in HIV-1 infected, ARV treatment-experienced adults
      who have documented resistance, or at least six months experience prior to screening with two
      or more different classes of ARV agents.

      Participants will be randomized in a 1:1 ratio to receive EVG plus background regimen
      (Elvitegravir group), or raltegravir plus background regimen (Raltegravir group). Due to
      known drug interactions, participants in the Elvitegravir group receiving RTV-boosted
      atazanavir (ATV) or RTV-boosted lopinavir (LPV) as part of their background regimen will
      receive elvitegravir at a lower dose (85 mg).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening

          -  Documented resistance or at least six months experience prior to screening with two or
             more different classes of antiretroviral agents

          -  Stable antiretroviral regimen for at least 30 days prior to screening: however,
             participants may discontinue the antiretroviral regimen after screening and remain off
             therapy until baseline at the discretion of the investigator

          -  Eligible to receive one of the fully-active ritonavir-boosted-PIs, and an allowed
             second agent

          -  Normal ECG

          -  Adequate renal function (estimated glomerular filtration rate according to the
             Cockcroft-Gault formula ≥ 60 mL/min)

          -  Hepatic transaminases ≤ 5 × upper limit of normal

          -  Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin

          -  Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥
             50,000/mm^3; hemoglobin ≥ 8.5 g/dL)

          -  Serum amylase < 1.5 × the upper limit of the normal range

          -  Negative serum pregnancy test (females of childbearing potential only)

          -  Males and females of childbearing potential must agree to use highly effective
             contraception methods

          -  Age ≥ 18 years

          -  Life expectancy ≥ 1 year

          -  Ability to understand and sign a written informed consent form

        Exclusion Criteria:

          -  New AIDS-defining condition diagnosed within the 30 days prior to screening

          -  Prior treatment with any HIV-1 integrase inhibitor

          -  Participants experiencing ascites

          -  Participants experiencing encephalopathy

          -  Females who are breastfeeding

          -  Positive serum pregnancy test at any time during the study (female of childbearing
             potential)

          -  Participants receiving ongoing therapy with any disallowed medication

          -  Current alcohol or substance use judged by the investigator to potentially interfere
             with study compliance

          -  Malignancy other than cutaneous Kaposi's sarcoma or basal cell 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 (except for the etravirine or maraviroc
             expanded access program), without prior approval from sponsor

          -  Any other clinical condition or prior therapy that would make participants unsuitable
             for the study

          -  Known hypersensitivity to study drug, metabolites or formulation excipients