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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/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 - The percentage of participants achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the FDA-defined Time to Loss of Virologic Response (TLOVR) algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.
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 - The percentage of participants achieving and maintaining confirmed HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.
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 - The percentage of participants achieving and maintaining confirmed HIV-1 RNA < 400 copies/mL at Week 48 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.
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 - The percentage of participants achieving and maintaining confirmed HIV-1 RNA < 400 copies/mL at Week 96 was analyzed using the FDA-defined TLOVR algorithm, which takes into account a patient's longitudinal viral load up to the predefined time point by considering patterns of suppression and rebounding.
Timepoint [3] 0 0
Week 96
Secondary outcome [4] 0 0
Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL) - Virologic response at Week 48 (percentage of participants with HIV-1 RNA < 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using the viral load along with study drug discontinuation status at the predefined time point within an allowed window of time.
Timepoint [4] 0 0
Week 48
Secondary outcome [5] 0 0
Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL) - Virologic response at Week 96 (percentage of participants with HIV-1 RNA < 50 copies/mL) was analyzed using the FDA-defined Snapshot algorithm, which defines a patient's virologic response status using the viral load along with study drug discontinuation status at the predefined time point within an allowed window of time.
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 - The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 50 copies/mL) up to Week 48 was estimated using the Kaplan-Meier method in the time to event analysis.
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 - The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 50 copies/mL) up to Week 96 was estimated using the Kaplan-Meier method in the time to event analysis.
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 - The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 400 copies/mL) up to Week 48 was estimated using the Kaplan-Meier method in the time to event analysis.
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 - The percentage of participants with pure virologic failure (HIV-1 RNA cutoff at 400 copies/mL) up to Week 96 was estimated using the Kaplan-Meier method in the time to event analysis.
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 - The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 48 was analyzed using the missing = failure method, where participants with missing data were considered as having failed to meet the criteria for evaluation.
Timepoint [10] 0 0
Week 48
Secondary outcome [11] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 - The percentage of participants with HIV-1 RNA < 50 copies/mL at Week 96 was analyzed using the missing = failure method.
Timepoint [11] 0 0
Week 96
Secondary outcome [12] 0 0
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48 - The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 48 was analyzed using the missing = failure method.
Timepoint [12] 0 0
Week 48
Secondary outcome [13] 0 0
Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96 - The percentage of participants with HIV-1 RNA < 400 copies/mL at Week 96 was analyzed using the missing = failure method.
Timepoint [13] 0 0
Week 96
Secondary outcome [14] 0 0
Change From Baseline in HIV-1 RNA at Week 48 - The change from baseline in log10 HIV-1 RNA (copies/mL) at Week 48 was analyzed.
Timepoint [14] 0 0
Baseline to Week 48
Secondary outcome [15] 0 0
Change From Baseline in HIV-1 RNA at Week 96 - The change from baseline in log10 HIV-1 RNA (copies/mL) at Week 96 was analyzed.
Timepoint [15] 0 0
Baseline to Week 96
Secondary outcome [16] 0 0
Change From Baseline in CD4 Cell Count at Week 48 - The change from baseline in CD4 cell count (cells/mm^3) at Week 48 was analyzed.
Timepoint [16] 0 0
Baseline to Week 48
Secondary outcome [17] 0 0
Change From Baseline in CD4 Cell Count at Week 96 - The change from baseline in CD4 cell count (cells/mm^3) at Week 96 was analyzed.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
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United States of America
State/province [16] 0 0
New Mexico
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
Country [20] 0 0
United States of America
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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
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Belgium
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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
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France
State/province [36] 0 0
Nice
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France
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Paris
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France
State/province [38] 0 0
Pessac
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France
State/province [39] 0 0
Toulouse
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Germany
State/province [40] 0 0
Bonn
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Germany
State/province [41] 0 0
Dusseldorf
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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
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Italy
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Milan
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Italy
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Rome
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Mexico
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D.f.
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Mexico
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Guanajuato
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Mexico
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Jalisco
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Mexico
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San Luis Potsi
Country [56] 0 0
Netherlands
State/province [56] 0 0
Rotterdam
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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/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
Other publications