Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00708162
First received: June 30, 2008
Last updated: April 21, 2016
Last verified: April 2016
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: EVG placebo
Drug: RAL placebo
Drug: Background regimen

  Participant Flow
  Hide Participant Flow

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 study visit occurred on 22 April 2015.

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 Elvitegravir (EVG) 85 or 150 mg tablet once daily plus raltegravir (RAL) placebo plus background regimen (1 fully-active ritonavir (RTV)-boosted protease inhibitor (PI) plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Raltegravir RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.

Participant Flow for 2 periods

Period 1:   Randomized Phase
    Elvitegravir   Raltegravir
STARTED   361   363 
Randomized and Treated   354   358 
COMPLETED   205   209 
NOT COMPLETED   156   154 
Randomized but Not Treated                7                5 
Participant Noncompliance                40                32 
Lost to Follow-up                34                34 
Withdrew Consent                31                22 
Lack of Efficacy                14                19 
Protocol Violation                10                11 
Adverse Event                8                12 
Investigator’s Discretion                7                10 
Death                2                9 
Pregnancy                3                0 

Period 2:   Open-Label Phase
    Elvitegravir   Raltegravir
STARTED   196 [1]   151 [2] 
COMPLETED   152   121 
NOT COMPLETED   44   30 
Lost to Follow-up                10                8 
Withdrew Consent                12                6 
Participant Noncompliance                7                7 
Lack of Efficacy                7                4 
Investigator's Discretion                3                2 
Death                3                1 
Adverse Event                1                2 
Other                1                0 
[1] 9 participants completing the Randomized Phase did not continue to the Open-Label Phase.
[2] 58 participants completing the Randomized Phase did not continue to the Open-Label Phase.



  Baseline Characteristics
  Hide Baseline Characteristics

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.
Safety Analysis Set: participants who were randomized and received at least one dose of study drug

Reporting Groups
  Description
Elvitegravir EVG 85 or 150 mg tablet once daily plus RAL placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Raltegravir RAL 400 mg tablet twice daily plus EVG placebo plus background regimen (1 fully-active RTV-boosted PI plus 1 or 2 additional agents) in the Randomized Phase, followed by EVG 85 or 150 mg tablet once daily plus background regimen in the Open-Label Phase.
Total Total of all reporting groups

Baseline Measures
   Elvitegravir   Raltegravir   Total 
Overall Participants Analyzed 
[Units: Participants]
 354   358   712 
Age 
[Units: Years]
Mean (Standard Deviation)
 44  (9.0)   45  (9.1)   45  (9.1) 
Gender 
[Units: Participants]
     
Female   60   67   127 
Male   294   291   585 
Ethnicity (NIH/OMB) 
[Units: Participants]
     
Hispanic or Latino   81   74   155 
Not Hispanic or Latino   272   283   555 
Unknown or Not Reported   1   1   2 
Race/Ethnicity, Customized 
[Units: Participants]
     
White   210   227   437 
Black or African American   128   119   247 
Asian   9   5   14 
American Indian or Alaska Native   3   3   6 
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 
[1] All randomized participants were analyzed for Region of Enrollment (elvitegravir arm: n = 361; raltegravir arm: n = 363)
HIV-1 RNA 
[Units: Log10 copies/mL]
Mean (Standard Deviation)
 4.26  (0.969)   4.27  (0.943)   4.26  (0.955) 
HIV-1 RNA category 
[Units: Participants]
     
≤ 100,000 copies/mL   263   267   530 
> 100,000 copies/mL   91   91   182 
Cluster of differentiation (CD4) Cell Count 
[Units: Cells/mm^3]
Mean (Standard Deviation)
 257.9  (204.31)   265.3  (207.04)   261.6  (205.57) 
HIV Disease Status 
[Units: Participants]
     
Asymptomatic   172   175   347 
Symptomatic HIV Infections   52   54   106 
AIDS   126   125   251 
Unknown   4   4   8 
Type of PI in Background Regimen (Excluding Ritonavir) [1] 
[Units: Participants]
     
atazanavir   64   53   117 
darunavir   202   206   408 
fosamprenavir   14   20   34 
lopinavir   68   72   140 
tipranavir   6   7   13 
[1] 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.
Type of NRTI in Background Regimen 
[Units: Participants]
     
tenofovir disoproxil fumarate   163   171   334 
emtricitabine/tenofovir disoproxil fumarate   91   66   157 
lamivudine   13   13   26 
abacavir   6   15   21 
abacavir/lamivudine   4   8   12 
lamivudine/zidovudine   6   5   11 
zidovudine   3   6   9 
didanosine   1   7   8 
emtricitabine   2   3   5 
no NRTI in background regimen   65   64   129 
Enfuvirtide (T-20) in background regimen 
[Units: Participants]
     
No   352   357   709 
Yes   2   1   3 
Etravirine in background regimen 
[Units: Participants]
     
No   309   303   612 
Yes   45   55   100 
Maraviroc in background regimen 
[Units: Participants]
     
No   330   340   670 
Yes   24   18   42 
Phenotypic Sensitivity Score [1] 
[Units: Participants]
     
1.0   5   4   9 
1.5   23   28   51 
2.0   309   313   622 
2.5   2   1   3 
3.0   14   10   24 
3.5   0   1   1 
No baseline PSS score   1   1   2 
[1] Phenotypic sensitivity score (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.
Chronic Hepatitis B (HBV) Infection Status 
[Units: Participants]
     
Indeterminant   1   0   1 
Negative   333   342   675 
Positive   17   13   30 
No baseline HBV measurement   3   3   6 
Chronic Hepatitis C (HCV) Infection Status 
[Units: Participants]
     
Indeterminant   2   2   4 
Negative   305   298   603 
Positive   44   55   99 
No baseline HCV measurement   3   3   6 


  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
  Hide Limitations and Caveats

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
  Hide More Information

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
2007-004225-26 ( EudraCT Number )
Study First Received: June 30, 2008
Results First Received: October 23, 2014
Last Updated: April 21, 2016
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