Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00708162




Registration number
NCT00708162
Ethics application status
Date submitted
30/06/2008
Date registered
2/07/2008
Date last updated
30/05/2016

Titles & IDs
Public title
Multicenter, Randomized, Double-Blind, Double-Dummy, Phase 3 Study of the Safety and Efficacy of Elvitegravir Versus Raltegravir
Scientific 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
Secondary ID [1] 0 0
2007-004225-26
Secondary ID [2] 0 0
GS-US-183-0145
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Elvitegravir
Treatment: Drugs - Raltegravir
Treatment: Drugs - EVG placebo
Treatment: Drugs - RAL placebo
Treatment: Drugs - Background regimen

Experimental: Elvitegravir - EVG 85 mg or 150 mg + RAL placebo + background regimen in the Randomized Phase, followed by EVG 85 mg or 150 mg + background regimen in the Open-Label Phase.
Participants receiving lopinavir/ritonavir (LPV/r) or atazanavir/ritonavir (ATV/r) as part of their background regimen will receive EVG 85 mg; all other participants will receive EVG 150 mg.

Active Comparator: Raltegravir - RAL 800 mg (400 mg twice daily) + EVG placebo + background regimen in the Randomized Phase, followed by EVG 85 mg or 150 mg + background regimen in the Open-Label Phase.
Participants receiving LPV/r or ATV/r as part of their background regimen in the Open-Label Phase will receive EVG 85 mg; all other participants will receive EVG 150 mg.


Treatment: Drugs: Elvitegravir
Elvitegravir (EVG) tablet administered orally once daily with food

Treatment: Drugs: Raltegravir
Raltegravir tablet administered orally twice daily according to prescribing information

Treatment: Drugs: EVG placebo
Placebo to match elvitegravir administered orally once daily

Treatment: Drugs: RAL placebo
RAL placebo administered orally twice daily.

Treatment: Drugs: Background regimen
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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 96
Timepoint [1] 0 0
Week 96
Secondary outcome [2] 0 0
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 48
Timepoint [2] 0 0
Week 48
Secondary outcome [3] 0 0
Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 96
Timepoint [3] 0 0
Week 96
Secondary outcome [4] 0 0
Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL)
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL)
Timepoint [5] 0 0
Week 96
Secondary outcome [6] 0 0
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 48
Timepoint [6] 0 0
Baseline to Week 48
Secondary outcome [7] 0 0
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 96
Timepoint [7] 0 0
Baseline to Week 96
Secondary outcome [8] 0 0
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 48
Timepoint [8] 0 0
Baseline to Week 48
Secondary outcome [9] 0 0
Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 96
Timepoint [9] 0 0
Baseline to Week 96
Secondary outcome [10] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Timepoint [10] 0 0
Week 48
Secondary outcome [11] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96
Timepoint [11] 0 0
Week 96
Secondary outcome [12] 0 0
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96
Timepoint [13] 0 0
Week 96
Secondary outcome [14] 0 0
Change From Baseline in HIV-1 RNA at Week 48
Timepoint [14] 0 0
Baseline to Week 48
Secondary outcome [15] 0 0
Change From Baseline in HIV-1 RNA at Week 96
Timepoint [15] 0 0
Baseline to Week 96
Secondary outcome [16] 0 0
Change From Baseline in CD4 Cell Count at Week 48
Timepoint [16] 0 0
Baseline to Week 48
Secondary outcome [17] 0 0
Change From Baseline in CD4 Cell Count at Week 96
Timepoint [17] 0 0
Baseline to Week 96

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/07/2008
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2015
Sample size
Target
Accrual to date
Final
724
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Ground Zero Medical Centre - Darlinghurst
Recruitment hospital [3] 0 0
Holdsworth House Medical Practice - Darlinghurst
Recruitment hospital [4] 0 0
St. Vincent's Hospital, Sydney - Darlinghurst
Recruitment hospital [5] 0 0
St George Hospital - Kogarah
Recruitment hospital [6] 0 0
East Sidney Doctors - Sidney
Recruitment hospital [7] 0 0
Albion Street Centre - Sydney
Recruitment hospital [8] 0 0
Westmead Hospital - Wentworthville
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
2010 - Sidney
Recruitment postcode(s) [5] 0 0
2010 - Sydney
Recruitment postcode(s) [6] 0 0
2145 - Wentworthville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Hawaii
Country [9] 0 0
United States of America
State/province [9] 0 0
Illinois
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New Mexico
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Pennsylvania
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
Belgium
State/province [24] 0 0
Antwerp
Country [25] 0 0
Belgium
State/province [25] 0 0
Brussels
Country [26] 0 0
Belgium
State/province [26] 0 0
Charleroi
Country [27] 0 0
Belgium
State/province [27] 0 0
Liege
Country [28] 0 0
Canada
State/province [28] 0 0
British Columbia
Country [29] 0 0
Canada
State/province [29] 0 0
Nova Scotia
Country [30] 0 0
Canada
State/province [30] 0 0
Ontario
Country [31] 0 0
Canada
State/province [31] 0 0
Quebec
Country [32] 0 0
Canada
State/province [32] 0 0
Winnipeg
Country [33] 0 0
France
State/province [33] 0 0
Le Kremlin Bicetre
Country [34] 0 0
France
State/province [34] 0 0
Montpellier
Country [35] 0 0
France
State/province [35] 0 0
Nantes
Country [36] 0 0
France
State/province [36] 0 0
Nice
Country [37] 0 0
France
State/province [37] 0 0
Paris
Country [38] 0 0
France
State/province [38] 0 0
Pessac
Country [39] 0 0
France
State/province [39] 0 0
Toulouse
Country [40] 0 0
Germany
State/province [40] 0 0
Bonn
Country [41] 0 0
Germany
State/province [41] 0 0
Dusseldorf
Country [42] 0 0
Germany
State/province [42] 0 0
Essen
Country [43] 0 0
Germany
State/province [43] 0 0
Frankfurt
Country [44] 0 0
Germany
State/province [44] 0 0
Hamburg
Country [45] 0 0
Germany
State/province [45] 0 0
Kiel
Country [46] 0 0
Germany
State/province [46] 0 0
Koln
Country [47] 0 0
Germany
State/province [47] 0 0
Munich
Country [48] 0 0
Italy
State/province [48] 0 0
Bergamo
Country [49] 0 0
Italy
State/province [49] 0 0
Brescia
Country [50] 0 0
Italy
State/province [50] 0 0
Milan
Country [51] 0 0
Italy
State/province [51] 0 0
Rome
Country [52] 0 0
Mexico
State/province [52] 0 0
D.f.
Country [53] 0 0
Mexico
State/province [53] 0 0
Guanajuato
Country [54] 0 0
Mexico
State/province [54] 0 0
Jalisco
Country [55] 0 0
Mexico
State/province [55] 0 0
San Luis Potsi
Country [56] 0 0
Netherlands
State/province [56] 0 0
Rotterdam
Country [57] 0 0
Portugal
State/province [57] 0 0
Amadora
Country [58] 0 0
Portugal
State/province [58] 0 0
Lisbon
Country [59] 0 0
Portugal
State/province [59] 0 0
Porto
Country [60] 0 0
Puerto Rico
State/province [60] 0 0
Ponce
Country [61] 0 0
Puerto Rico
State/province [61] 0 0
San Juan
Country [62] 0 0
Spain
State/province [62] 0 0
Alicante
Country [63] 0 0
Spain
State/province [63] 0 0
Barcelona
Country [64] 0 0
Spain
State/province [64] 0 0
Cordoba
Country [65] 0 0
Spain
State/province [65] 0 0
Elche
Country [66] 0 0
Spain
State/province [66] 0 0
Granada
Country [67] 0 0
Spain
State/province [67] 0 0
Madrid
Country [68] 0 0
Spain
State/province [68] 0 0
Malaga
Country [69] 0 0
Spain
State/province [69] 0 0
Santa Cruz de Tenerife
Country [70] 0 0
Spain
State/province [70] 0 0
Sevilla
Country [71] 0 0
Spain
State/province [71] 0 0
Vigo
Country [72] 0 0
Switzerland
State/province [72] 0 0
Zurich
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Edinburgh
Country [74] 0 0
United Kingdom
State/province [74] 0 0
London
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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).
Trial website
https://clinicaltrials.gov/ct2/show/NCT00708162
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Javier Szwarcberg, MD, MPH
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00708162