Phase 3
Completed N=724
Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Elvitegravir Versus Raltegravir
Source: ClinicalTrials.gov NCT00708162 ↗Enrolled (actual)
724
Serious AEs
23.5%
Results posted
Nov 2014
Primary outcomePrimary: Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 — 59.0; 57.8 percentage of participants
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).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48 |
59.0; 57.8 | — |
| SECONDARY Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 96 |
47.6; 45.0 | — |
| SECONDARY Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 48 |
68.1; 67.2 | — |
| SECONDARY Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 96 |
57.0; 56.1 | — |
| SECONDARY Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL) |
59.8; 57.5 | — |
| SECONDARY Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL) |
52.4; 53.0 | — |
| SECONDARY Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 48 |
35; 35 | — |
| SECONDARY Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 96 |
45; 46 | — |
| SECONDARY Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 48 |
24; 24 | — |
| SECONDARY Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 96 |
32; 31 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 |
61.0; 60.7 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 |
53.6; 56.4 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 |
70.1; 72.1 | — |
| SECONDARY Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 |
61.3; 63.0 | — |
| SECONDARY Change From Baseline in HIV-1 RNA at Week 48 |
-2.17; -2.18 | — |
| SECONDARY Change From Baseline in HIV-1 RNA at Week 96 |
-2.26; -2.31 | — |
| SECONDARY Change From Baseline in CD4 Cell Count at Week 48 |
138; 147 | — |
| SECONDARY Change From Baseline in CD4 Cell Count at Week 96 |
205; 198 | — |
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
Data sourced from ClinicalTrials.gov (NCT00708162). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.