A Study to Evaluate the Safety and Efficacy of Raltegravir (MK0518) in HIV-Infected Patients Failing Current Antiretroviral Therapies (0518-019 EXT2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00293254
First received: February 15, 2006
Last updated: August 30, 2013
Last verified: August 2013
Results First Received: August 20, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: raltegravir potassium
Drug: Comparator: placebo

  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

Phase 3; First Patient In: 08-Mar-2006; Last Patient Last Visit (LPLV) for Week 48: 31-Jul-2007; Extension Study LPLV Week 240: May 2011

53 sites (US, Brazil, Canada, Colombia, Mexico, and Puerto Rico).


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Patients failed prior antiretroviral therapy (HIV RNA >1000 copies/mL), and had documented resistance to at least one drug in each class of licensed oral antiretroviral therapy (Nucleoside Reverse Transcriptase inhibitors, Non-Nucleoside Reverse Transcriptase Inhibitors, and Protease Inhibitors). All patients must have met laboratory criteria.

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. + OBT No text entered.
Placebo + OBT No text entered.

Participant Flow for 4 periods

Period 1:   Primary Study - Double-Blind Week 0-48
    Raltegravir 400 mg b.i.d. + OBT     Placebo + OBT  
STARTED     232     119  
Treated     230     119  
Continuing in Double-Blind     177 [1]   55 [2]
COMPLETED     177     55  
NOT COMPLETED     55     64  
Never Treated                 2                 0  
Adverse Event                 2                 1  
Death                 5                 2  
Lack of Efficacy                 2                 2  
Lost to Follow-up                 3                 1  
Withdrawal by Subject                 5                 1  
Moved or trial terminated at site                 1                 0  
Entered OLPVF Phase                 35                 57  
[1] Excludes participants who entered the Open-Label Post-Virologic Failure (OLPVF) Phase
[2] Excludes participants who entered the OLPVF phase

Period 2:   Extension - Double-Blind Week 49-156
    Raltegravir 400 mg b.i.d. + OBT     Placebo + OBT  
STARTED     177     54 [1]
COMPLETED     120     25  
NOT COMPLETED     57     29  
Adverse Event                 4                 1  
Death                 4                 1  
Lack of Efficacy                 3                 4  
Lost to Follow-up                 3                 3  
Withdrawal by Subject                 12                 8  
Participant Moved/Site Stopped Trial                 6                 3  
Other Reason                 10                 2  
Entered OLPVF Phase                 15                 7  
[1] 1 of 55 participants who completed Week 48 did not enter the extension study.

Period 3:   Extension - Open-Label Week 157-240
    Raltegravir 400 mg b.i.d. + OBT     Placebo + OBT  
STARTED     120     19 [1]
COMPLETED     110     18  
NOT COMPLETED     10     1  
Adverse Event                 2                 1  
Lack of Efficacy                 1                 0  
Withdrawal by Subject                 1                 0  
Lost to Follow-up                 2                 0  
Other Reason                 4                 0  
[1] 6 of 25 participants who completed the double-blind phase did not enter this open-label phase.

Period 4:   Open-Label Post Virologic Failure Phase
    Raltegravir 400 mg b.i.d. + OBT     Placebo + OBT  
STARTED     50 [1]   64 [1]
COMPLETED     19     37  
NOT COMPLETED     31     27  
Adverse Event                 4                 7  
Lack of Efficacy                 16                 14  
Withdrawal by Subject                 6                 3  
Lost to Follow-up                 3                 0  
Participant Moved/Site Stopped Trial                 1                 1  
Other Reason                 1                 2  
[1] Number of participants who failed treatment and consented to enter the OLPVF phase



  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.
No text entered.

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. + OBT No text entered.
Placebo + OBT No text entered.
Total Total of all reporting groups

Baseline Measures
    Raltegravir 400 mg b.i.d. + OBT     Placebo + OBT     Total  
Number of Participants  
[units: participants]
  230     119     349  
Age  
[units: Years]
Mean ( Full Range )
  45.3  
  ( 16 to 67 )  
  46.5  
  ( 17 to 70 )  
  45.7  
  ( 16 to 70 )  
Gender  
[units: participants]
     
Female     20     12     32  
Male     210     107     317  
Race/Ethnicity, Customized  
[units: Participants]
     
White     127     77     204  
Black     47     21     68  
Asian     2     1     3  
Hispanic     47     18     65  
Native American     1     0     1  
Other     6     2     8  
Cluster of Differentiation 4 (CD4) Cell Count  
[units: cells/mm^3]
Mean ( Full Range )
  146  
  ( 1 to 757 )  
  163  
  ( 0 to 674 )  
  152  
  ( 0 to 757 )  
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA)  
[units: copies/mL]
Geometric Mean ( Full Range )
  49159  
  ( 200 to 750000 )  
  47850  
  ( 200 to 750000 )  
  48709  
  ( 200 to 750000 )  



  Outcome Measures
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1.  Primary:   Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 16   [ Time Frame: 16 Weeks ]

2.  Primary:   Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 48   [ Time Frame: 48 Weeks ]

3.  Primary:   Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <400 Copies/mL   [ Time Frame: 156 Weeks ]

4.  Primary:   Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <400 Copies/mL   [ Time Frame: 240 Weeks ]

5.  Secondary:   Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 16   [ Time Frame: 16 Weeks ]

6.  Secondary:   Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 48   [ Time Frame: 48 Weeks ]

7.  Secondary:   Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <50 Copies/mL   [ Time Frame: 156 Weeks ]

8.  Secondary:   Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL   [ Time Frame: 240 Weeks ]
  Hide Outcome Measure 8

Measure Type Secondary
Measure Title Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL
Measure Description Percentage of participants who achieved HIV RNA <50 copies/mL at Week 240
Time Frame 240 Weeks  
Safety Issue No  

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.
Participants who experienced virologic failure after Week 16 are also counted as treatment failures for the subsequent virologic efficacy analyses.

Reporting Groups
  Description
Raltegravir 400 mg b.i.d. + OBT Raltegravir 400 mg b.i.d. plus OBT includes all participants initially randomized to raltegravir. Those who did not experience virologic failure by Week 156 may have continued into the open-label phase. During the open-label phase, these participants continued to receive raltegravir plus OBT until Week 240.
Placebo + OBT Placebo plus OBT includes all participants initially randomized to placebo. Those who did not experience virologic failure by Week 156 may have continued into the open-label phase. During the open-label phase, these participants received raltegravir plus OBT until Week 240.

Measured Values
    Raltegravir 400 mg b.i.d. + OBT     Placebo + OBT  
Number of Participants Analyzed  
[units: participants]
  230     119  
Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL  
[units: Percentage¬†of¬†Participants]
Number ( 95% Confidence Interval )
  41.3  
  ( 34.9 to 48.0 )  
  13.4  
  ( 7.9 to 20.9 )  

No statistical analysis provided for Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL



9.  Secondary:   Double-Blind Extension - Week 156: Percentage of Participants Without Loss of Virologic Response   [ Time Frame: 156 Weeks ]

10.  Secondary:   Change From Baseline in HIV RNA (Log 10 Copies/mL) at Week 16   [ Time Frame: Baseline and Week 16 ]

11.  Secondary:   Change From Baseline in HIV RNA (log10 Copies/mL) at Week 48   [ Time Frame: Baseline and Week 48 ]

12.  Secondary:   Double-Blind Extension - Week 156: Change From Baseline in HIV RNA (log10 Copies/mL)   [ Time Frame: Baseline and Week 156 ]

13.  Secondary:   Open-Label Extension - Week 240: Change From Baseline in HIV RNA (log10 Copies/mL)   [ Time Frame: Baseline and Week 240 ]

14.  Secondary:   Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 16   [ Time Frame: Baseline and Week 16 ]

15.  Secondary:   Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 48   [ Time Frame: Baseline and Week 48 ]

16.  Secondary:   Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count(Cells/mm^3)   [ Time Frame: Baseline and Week 156 ]

17.  Secondary:   Open-Label Extension - Week 240: Change From Baseline in CD4 Cell Count (Cells/mm^3)   [ Time Frame: Baseline and Week 240 ]


  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
Adverse events are reported by original treatment group for the entire 240-week study, including double-blind, open-label, and OLPVF phases; 83 of 119 participants in the placebo group also received raltegravir in the open-label or OLPVF phase.


  More Information