Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Elvitegravir Versus Raltegravir

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).

Timeline

Start

2008-07

Primary completion

2010-12

Completion

2015-04

Outcome

Met primary endpoint

paper treatment difference 1·1%, 95% CI -6·0 to 8·2), meeting the criterion for non-inferiority (p=0·001). PMID 22015077 ↗

release “Responses at 48 weeks of elvitegravir met the statistical criteria of non-inferiority as compared to raltegravir” gilead.com ↗

release “its investigational antiretroviral elvitegravir, a novel oral integrase inhibitor being evaluated for the treatment of HIV-1 infection, was non-inferior to the integrase inhibitor raltegravir” gilead.com ↗

release “Phase 3 clinical trial results showing that the integrase inhibitor elvitegravir dosed once daily is non-inferior to raltegravir dosed twice daily among treatment-experienced HIV patients.” gilead.com ↗

Publications

• Results Molina JM, Lamarca A, Andrade-Villanueva J, Clotet B, Clumeck N, Liu YP, Zhong L, Margot N, Cheng AK, Chuck SL; Study 145 Team. Efficacy and safety of once daily elvitegravir versus twice daily raltegravir in treatment-experienced patients with HIV-1 receiving a ritonavir-boosted protease inhibitor: randomised, double-blind, phase 3, non-inferiority study. Lancet Infect Dis. 2012 Jan;12(1):27-35. doi: 10.1016/S1473-3099(11)70249-3. Epub 2011 Oct 18.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Raltegravir	Other / unclassified	400 mg	—
Subject	elvitegravir	Small molecule	85 mg	—
Subject	elvitegravir	Small molecule	150 mg	—
Background	Abacavir	Other / unclassified	—	—
Background	Atazanavir	Other / unclassified	—	—
Background	Combivir	Unknown	—	—
Background	Darunavir	Small molecule	—	—
Background	Didanosine	Small molecule	—	—
Background	EPZICOM	Unknown	—	—
Background	Enfuvirtide	Peptide	—	—
Background	Etravirine	Small molecule	—	—
Background	Fosamprenavir	Small molecule	—	—
Background	Lamivudine	Other / unclassified	—	—
Background	Lopinavir	Other / unclassified	—	—
Background	Maraviroc	Other / unclassified	—	—
Background	Ritonavir	Other / unclassified	—	—
Background	Tenofovir disoproxil fumarate	Small molecule	—	—
Background	Tipranavir	Small molecule	—	—
Background	Truvada	Unknown	—	—
Background	Zidovudine	Small molecule	—	—
Background	emtricitabine	Other / unclassified	—	—

Indications