Phase 3 Study of the Safety and Efficacy of Ritonavir-Boosted Elvitegravir (EVG/r) Versus Raltegravir (RAL)

This study has been terminated.
(Due to declining numbers of patients with unsuppressed viremia, Gilead combined the studies GS-US-183-0144 and 0145 into one study (GS-US-183-0145).)
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00707733
First received: June 27, 2008
Last updated: February 11, 2014
Last verified: February 2014
  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
Drug: Placebo to match elvitegravir
Drug: Placebo to match raltegravir
Drug: Background regimen
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel 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:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Proportion of subjects achieving and maintaining confirmed HIV-1 RNA less than 50 copies/mL through Week 48. [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Proportion of subjects achieving and maintaining confirmed HIV-1 RNA less than 400 copies/mL through Week 48. [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]
  • Proportion of subjects with HIV-1 RNA < 50 copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Change from baseline in log10 HIV-1 RNA (copies/mL) at Week 48 [ Time Frame: Baseline to Weeks 48 ] [ Designated as safety issue: No ]
  • Change from baseline in CD4+ cell count at Week 48 [ Time Frame: Baseline to Week 48 ] [ Designated as safety issue: No ]

Enrollment: 214
Study Start Date: June 2008
Study Completion Date: December 2010
Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Elvitegravir
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
Drug: Elvitegravir
Elvitegravir administered orally once daily with food
Drug: Placebo to match raltegravir
Placebo to match raltegravir administered as a tablet orally twice daily
Drug: Background regimen
Background regimen (BR) administered according to prescribing information, and containing 1 fully-active ritonavir-boosted protease inhibitor (PI/r) plus 1 or 2 additional agents. Agents may include atazanavir, abacavir, darunavir, didanosine, emtricitabine, enfuvirtide, etravirine, fosamprenavir, lamivudine, lopinavir, maraviroc, tenofovir disoproxil fumarate, tipranavir, and or zidovudine
Active Comparator: Raltegravir
Raltegravir 400 mg BID + BR
Drug: Raltegravir
Raltegravir administered orally twice daily according to the prescribing information
Other Name: Isentress
Drug: Placebo to match elvitegravir
Placebo to match elvitegravir administered as a tablet orally once daily
Drug: Background regimen
Background regimen (BR) administered according to prescribing information, and containing 1 fully-active ritonavir-boosted protease inhibitor (PI/r) plus 1 or 2 additional agents. Agents may include atazanavir, abacavir, darunavir, didanosine, emtricitabine, enfuvirtide, etravirine, fosamprenavir, lamivudine, lopinavir, maraviroc, tenofovir disoproxil fumarate, tipranavir, and or zidovudine

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 once daily (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.

Two identical Phase 3 studies of elvitegravir tablets boosted with ritonavir are currently ongoing in treatment-experienced adults with HIV-1 infection. Initiated in July 2008, Study GS-US-183-0144 (planned N=700) is being conducted in the US and Puerto Rico and Study GS-US-183-0145 (planned N=700) is being conducted in Europe, Australia, Mexico and Canada. Given the declining numbers of patients with unsuppressed viremia, Gilead is combining the two ongoing studies into a single, global Phase 3 study (GS-US-183-0145) to enroll a total of 700 subjects. The protocol amendment enables the transfer of subjects from Study GS-US-183-0144 into study GS-US-183-0145.

  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
  • Subjects must have 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
  • Subjects must be 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 the upper limit of the normal range (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:

  • A 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 without prior approval from sponsor
  • Any other clinical condition or prior therapy that would make subject unsuitable for the study
  • Known hypersensitivity to study drug, metabolites or formulation excipients
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00707733

Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Steven Chuck, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00707733     History of Changes
Other Study ID Numbers: GS-US-183-0144
Study First Received: June 27, 2008
Last Updated: February 11, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV
HIV 1
Treatment Experienced

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Immune System Diseases
Immunologic Deficiency Syndromes
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Sexually Transmitted Diseases
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Virus Diseases
Ritonavir
Anti-HIV Agents
Anti-Infective Agents
Anti-Retroviral Agents
Antiviral Agents
Enzyme Inhibitors
HIV Protease Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014