Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL) - Full Text View

Sponsor:	Gilead Sciences
Information provided by (Responsible Party):	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00708162

Purpose

The purpose of this study is to compare the safety, tolerability and efficacy of a regimen containing once-daily ritonavir-boosted elvitegravir or twice-daily raltegravir added to a background regimen in HIV-1 infected, antiretroviral treatment-experienced adults who have documented resistance, or at least six months experience prior to screening with two or more different classes of antiretroviral agents.

Condition	Intervention	Phase
HIV Infection	Drug: elvitegravir Drug: Raltegravir	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL) Each Administered With a Background Regimen in HIV-1 Infected, Antiretroviral Treatment-Experienced Adults

Resource links provided by NLM:

Genetics Home Reference related topics: complement factor I deficiency

MedlinePlus related topics: HIV/AIDS

Drug Information available for: Ritonavir Raltegravir GS 9137 Raltegravir potassium

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

The primary efficacy endpoint is the proportion of subjects achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL through Week 48. [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

To evaluate the efficacy, safety and tolerability of the two treatment arms through 48 weeks of treatment. [ Time Frame: 96 weeks ] [ Designated as safety issue: No ]

Enrollment:	712
Study Start Date:	September 2008
Estimated Study Completion Date:	March 2014
Primary Completion Date:	December 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Ritonavir-boosted elvitegravir 150 mg QD (ritonavir-boosted elvitegravir 85 mg QD for subjects taking atazanavir/r or lopinavir/r as part of their BR) + BR (N = 350)	Drug: elvitegravir Elvitegravir 85 mg, 150 mg tablets or matching placebo administered orally QD (with ritonavir-boosted PI) to be taken with food.
Active Comparator: 2 Raltegravir 400 mg BID + BR (N = 350)	Drug: Raltegravir Raltegravir 400 mg tablets or matching placebo administered orally BID and to be taken according to the prescribing information. Other Name: Isentress

Detailed Description:

This is a double-blind, double-dummy, multicenter, randomized, active-controlled study to assess the safety and efficacy of a regimen containing ritonavir-boosted elvitegravir versus raltegravir, each administered with a background regimen (BR) containing a fully-active ritonavir-boosted protease inhibitor (PI) and a second single agent in HIV-1 infected, antiretroviral treatment-experienced adults. Subjects will be randomized in a 1:1 ratio to one of the following two treatment arms:

Treatment Arm 1: Ritonavir-boosted elvitegravir 150 mg QD (ritonavir-boosted elvitegravir 85 mg QD for subjects taking atazanavir/r or lopinavir/r as part of their BR) + BR (N = 350)
Treatment Arm 2: Raltegravir 400 mg BID + BR (N = 350)

Due to known pharmacokinetic interactions, subjects who are taking atazanavir/r (ATV/r) or lopinavir/r (LPV/r) as part of their BR will receive elvitegravir 85 mg if randomized to Treatment Arm 1.

The BR shall be constructed by the investigator based on viral resistance testing and shall be composed of a fully-active ritonavir-boosted PI and a second single agent.

The fully-active PI is defined by phenotypic resistance analysis. For phenotypic susceptibility, fully active is defined as being below the lower clinical or biological cutoff. The following ritonavir-boosted PIs are allowed to be prescribed by the investigator as part of the BR: atazanavir/r, darunavir/r, fosamprenavir/r, lopinavir/r, or tipranavir/r. Subjects must take their ritonavir dose based on the dosing schedule indicated in the prescribing information for the PI; no additional ritonavir is required to be taken with elvitegravir. No other marketed PIs will be allowed as part of the BR due to unknown pharmacokinetic interactions.

The second single agent may or may not be fully-active and can be one nucleoside or nucleotide reverse transcriptase inhibitor (NRTI), etravirine, maraviroc, or T-20. However, the second single agent must not include an integrase inhibitor; the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz, nevirapine, or delavirdine (due to unknown pharmacokinetic interactions); or fixed-dose combination antiretroviral therapies.

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 greater than or equal to 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 and must remain on screening regimen until the baseline visit
Eligible to receive one of the fully-active ritonavir-boosted-PIs, and an allowed second agent
Normal ECG
Adequate renal function
Hepatic transaminases less than or equal to 2.5 x upper limit of normal
Total bilirubin less than or equal to 1.5 mg/dL, or normal direct bilirubin
Adequate hematologic function
Prothrombin Time less than or equal to 1.25 x ULN
Serum amylase less than 1.5 x ULN
Negative serum pregnancy test (females of childbearing potential only)
Males and females of childbearing potential must agree to use highly effective contraception methods
Age greater than or equal to 18 years
Life expectancy greater than or equal to 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
Subjects experiencing ascites
Subjects experiencing encephalopathy
Females who are breastfeeding
Positive serum pregnancy test at any time during the study (female of childbearing potential)
Subjects 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 therapy
Participation in any other clinical trial (except for the etravirine expanded access program), without prior approval from sponsor
Any other clinical condition or prior therapy that would make subjects unsuitable for the study
Known hypersensitivity to study drug, metabolites or formulation excipients

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00708162

Show 182 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Javier Szwarcberg, MD, MPH

Gilead Sciences

More Information

No publications provided by Gilead Sciences

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Epub 2011 Oct 18.

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT00708162 History of Changes
Other Study ID Numbers:	GS-US-183-0145, EudraCT Number:2007-004225-26
Study First Received:	June 30, 2008
Last Updated:	September 14, 2011
Health Authority:	United States: Food and Drug Administration; Australia: Human Research Ethics Committee; Belgium: Federal Agency for Medicinal Products and Health Products; Canada: Health Canada; France: Afssaps - French Health Products Safety Agency; Germany: Federal Institute for Drugs and Medical Devices; Ireland: Irish Medicines Board; Italy: Ministry of Health; Netherlands: The Central Committee on Research Involving Human Subjects (CCMO); Portugal: National Pharmacy and Medicines Institute; Spain: Spanish Agency of Medicines; Switzerland: Swissmedic; United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:

HIV
HIV I
Treatment Experienced

Additional relevant MeSH terms:

HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases

Ritonavir
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 09, 2012