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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00708162
First received: June 30, 2008
Last updated: October 30, 2014
Last verified: October 2014
Results First Received: October 23, 2014  
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
Condition: HIV Infection
Interventions: Drug: Elvitegravir
Drug: Raltegravir
Drug: Placebo to match elvitegravir
Drug: Placebo to match raltegravir
Drug: Background regimen

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants were enrolled in a total of 161 study sites in Australia, Europe, and North America. The first participant was screened on 19 June 2008. The last participant observation for the Week 96 analysis was on 29 November 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
1335 participants were screened.

Reporting Groups
  Description
Elvitegravir Participants were randomized to receive elvitegravir (EVG), plus placebo to match raltegravir (RAL), plus background regimen.
Raltegravir Participants were randomized to receive RAL, plus placebo to match EVG, plus background regimen.

Participant Flow:   Overall Study
    Elvitegravir     Raltegravir  
STARTED     361     363  
Randomized and Treated     354     358  
COMPLETED     0     0  
NOT COMPLETED     361     363  
Randomized but not treated                 7                 5  
Lost to Follow-up                 31                 33  
Subject noncompliance                 36                 28  
Withdrawal by Subject                 30                 18  
Lack of Efficacy                 13                 15  
Protocol Violation                 10                 11  
Adverse Event                 8                 11  
Physician Decision                 7                 10  
Death                 2                 9  
Pregnancy                 1                 0  
Participant Still on Study                 216                 223  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT Analysis Set: participants randomized and treated with study drug and no critical protocol violations

Reporting Groups
  Description
Elvitegravir Participants were randomized to receive elvitegravir (EVG), plus placebo to match raltegravir (RAL), plus background regimen.
Raltegravir Participants were randomized to receive RAL, plus placebo to match EVG, plus background regimen.
Total Total of all reporting groups

Baseline Measures
    Elvitegravir     Raltegravir     Total  
Number of Participants  
[units: participants]
  351     351     702  
Age  
[units: years]
Mean ± Standard Deviation
  44  ± 9.0     45  ± 9.2     45  ± 9.1  
Gender  
[units: participants]
     
Female     59     67     126  
Male     292     284     576  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     79     73     152  
Not Hispanic or Latino     271     277     548  
Unknown or Not Reported     1     1     2  
Race/Ethnicity, Customized  
[units: participants]
     
White     211     226     437  
Black or African American     125     113     238  
Asian     9     5     14  
American Indian or Alaska Native     2     3     5  
Native Hawaiian or Other Pacific Islander     1     0     1  
Other     3     4     7  
Region of Enrollment [1]
[units: participants]
     
United States     230     223     453  
Portugal     10     11     21  
Spain     14     20     34  
United Kingdom     6     5     11  
Italy     7     10     17  
France     16     9     25  
Mexico     26     25     51  
Canada     16     18     34  
Puerto Rico     8     14     22  
Belgium     5     6     11  
Australia     17     12     29  
Germany     6     8     14  
Netherlands     0     2     2  
HIV-1 RNA  
[units: log10┬ácopies/mL]
Mean ± Standard Deviation
  4.26  ± 0.971     4.27  ± 0.944     4.26  ± 0.957  
HIV-1 RNA category  
[units: participants]
     
≤ 100,000 copies/mL     261     261     522  
> 100,000 copies/mL     90     90     180  
Cluster of differentiation (CD4) Cell Count  
[units: cells/mm^3]
Mean ± Standard Deviation
  259  ± 204.4     264  ± 207.9     262  ± 206.1  
HIV Disease Status  
[units: participants]
     
Asymptomatic     170     168     338  
Symptomatic HIV Infections     51     54     105  
AIDS     126     125     251  
Unknown     4     4     8  
Type of PI in Background Regimen (Excluding Ritonavir) [2]
[units: participants]
     
atazanavir     61     51     112  
darunavir     202     207     409  
fosamprenavir     14     18     32  
lopinavir     68     68     136  
tipranavir     6     7     13  
Type of NRTI in Background Regimen [3]
[units: participants]
     
tenofovir disoproxil fumarate     163     171     334  
emtricitabine/tenofovir disoproxil fumarate     91     67     158  
lamivudine     11     13     24  
abacavir     5     12     17  
abacavir/lamivudine     4     8     12  
lamivudine/zidovudine     6     5     11  
zidovudine     3     6     9  
didanosine     1     5     6  
emtricitabine     2     2     4  
Enfuvirtide (T-20) in background regimen  
[units: participants]
     
No     349     350     699  
Yes     2     1     3  
Etravirine in background regimen  
[units: participants]
     
No     306     297     603  
Yes     45     54     99  
Maraviroc in background regimen  
[units: participants]
     
No     327     333     660  
Yes     24     18     42  
Phenotypic Sensitivity Score [4]
[units: participants]
     
1     5     4     9  
1.5     23     28     51  
2     306     306     612  
2.5     2     1     3  
3     14     10     24  
3.5     0     1     1  
Chronic Hepatitis B (HBV) Infection Status [5]
[units: participants]
     
Indeterminant     1     0     1  
Negative     330     336     666  
Positive     17     12     29  
Chronic Hepatitis C (HCV) Infection Status [6]
[units: participants]
     
Indeterminant     2     2     4  
Negative     302     292     594  
Positive     44     54     98  
[1] All randomized participants were analyzed for Region of Enrollment (elvitegravir arm: n = 361; raltegravir arm: n = 363)
[2] One participant in the raltegravir group switched from darunavir to fosamprenavir at Day 5, and is counted only in the number receiving darunavir at baseline.
[3] Only participants who had an NRTI in their background regimen were reported.
[4] 350 participants in the EVG arm and 350 participants in the RAL arm had baseline measurements for phenotypic sensitivity score (PSS). PSS was calculated by summing up drug susceptibility values (1=sensitive; 0.5=partially sensitive; 0=resistance or reduced susceptibility) on all drugs in the baseline background regimen. For subjects naive to enfuvirtide (or maraviroc), a score of 1 was assigned for enfuvirtide (or maraviroc). Higher scores correspond to increased sensitivity.
[5] 348 participants in the EVG arm and 348 participants in the RAL arm had baseline measurements for chronic HBV infection status.
[6] 348 participants in the EVG arm and 348 participants in the RAL arm had baseline measurements for chronic HCV infection status.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 48   [ Time Frame: Week 48 ]

2.  Secondary:   Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 50 Copies/mL at Week 96   [ Time Frame: Week 96 ]

3.  Secondary:   Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 48   [ Time Frame: Week 48 ]

4.  Secondary:   Percentage of Participants Achieving and Maintaining Confirmed HIV-1 RNA < 400 Copies/mL at Week 96   [ Time Frame: Week 96 ]

5.  Secondary:   Virologic Response at Week 48 (HIV-1 RNA < 50 Copies/mL)   [ Time Frame: Week 48 ]

6.  Secondary:   Virologic Response at Week 96 (HIV-1 RNA < 50 Copies/mL)   [ Time Frame: Week 96 ]

7.  Secondary:   Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 48   [ Time Frame: Baseline to Week 48 ]

8.  Secondary:   Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 50 Copies/mL) up to Week 96   [ Time Frame: Baseline to Week 96 ]

9.  Secondary:   Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 48   [ Time Frame: Baseline to Week 48 ]

10.  Secondary:   Percentage of Participants With Pure Virologic Failure (HIV-1 RNA Cutoff at 400 Copies/mL) up to Week 96   [ Time Frame: Baseline to Week 96 ]

11.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48   [ Time Frame: Week 48 ]

12.  Secondary:   Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96   [ Time Frame: Week 96 ]

13.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 48   [ Time Frame: Week 48 ]

14.  Secondary:   Percentage of Participants With HIV-1 RNA < 400 Copies/mL at Week 96   [ Time Frame: Week 96 ]

15.  Secondary:   Change From Baseline in HIV-1 RNA at Week 48   [ Time Frame: Baseline to Week 48 ]

16.  Secondary:   Change From Baseline in HIV-1 RNA at Week 96   [ Time Frame: Baseline to Week 96 ]

17.  Secondary:   Change From Baseline in CD4 Cell Count at Week 48   [ Time Frame: Baseline to Week 48 ]

18.  Secondary:   Change From Baseline in CD4 Cell Count at Week 96   [ Time Frame: Baseline to Week 96 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
10 participants from a single study site were excluded from Intent-to-Treat (ITT) Analysis Set due to critical and multiple protocol violations (elvitegravir arm: n = 3; raltegravir arm: n = 7).


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Clinical Trial Disclosures
Organization: Gilead Sciences, Inc.
e-mail: ClinicalTrialDisclosures@gilead.com


Publications of Results:

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00708162     History of Changes
Obsolete Identifiers: NCT00707733
Other Study ID Numbers: GS-US-183-0145, EudraCT Number:2007-004225-26
Study First Received: June 30, 2008
Results First Received: October 23, 2014
Last Updated: October 30, 2014
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 - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
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