A Study to Evaluate the Safety and Efficacy of Raltegravir (MK0518) in HIV-Infected Patients Failing Current Antiretroviral Therapies (MK0518-018 EXT2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00293267
First received: February 14, 2006
Last updated: October 22, 2013
Last verified: October 2013
Results First Received: August 18, 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: Mar 2006; Last Patient Last Visit (LPLV) Week 48: Aug 2007; 61 of 63 sites in Australia, Belgium, Denmark, France, Germany, Italy, Peru, Portugal, Spain, Switzerland, Taiwan, Thailand randomized patients. Extension Study LPLV Week 240: June 2011

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     234     118  
Treated     232     118  
Continuing in Double-Blind     193 [1]   50  
COMPLETED     193     50  
NOT COMPLETED     41     68  
Never Treated                 2                 0  
Adverse Event                 1                 1  
Death                 3                 3  
Lack of Efficacy                 0                 2  
Lost to Follow-up                 1                 1  
Withdrawal by Subject                 1                 1  
Entered OLPVF Phase                 33                 60  
[1] Excludes participants who entered the open-label post virological failure (OLPVF) phase

Period 2:   Extension - Double-Blind Week 49-156
    Raltegravir 400 mg b.i.d. + OBT     Placebo + OBT  
STARTED     191 [1]   50  
COMPLETED     139     35  
NOT COMPLETED     52     15  
Adverse Event                 1                 4  
Lack of Efficacy                 7                 1  
Lost to Follow-up                 4                 0  
Withdrawal by Subject                 13                 4  
Death                 3                 0  
Participant relocated or site terminated                 2                 0  
Other Reason                 7                 0  
Entered OLPVF Phase                 15                 6  
[1] 2 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     131 [1]   28 [2]
COMPLETED     111     26  
NOT COMPLETED     20     2  
Adverse Event                 5                 0  
Lack of Efficacy                 7                 0  
Lost to Follow-up                 1                 0  
Withdrawal by Subject                 2                 1  
Participant relocated or site terminated                 2                 0  
Other Reason                 3                 1  
[1] 8 of 139 participants who completed the double-blind phase did not enter this open-label phase
[2] 7 of 35 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     48 [1]   66 [1]
COMPLETED     15     29  
NOT COMPLETED     33     37  
Adverse Event                 2                 3  
Lack of Efficacy                 23                 19  
Withdrawal by Subject                 2                 4  
Lost to Follow-up                 2                 2  
Laboratory Adverse Event                 0                 2  
Participant Moved or Site Terminated                 0                 2  
Other Reason                 4                 5  
[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]
  232     118     350  
Age  
[units: Years]
Mean ( Full Range )
  46.1  
  ( 16 to 74 )  
  43.7  
  ( 19 to 64 )  
  45.3  
  ( 16 to 74 )  
Gender  
[units: participants]
     
Female     37     15     52  
Male     195     103     298  
Race/Ethnicity, Customized  
[units: participants]
     
White     174     96     270  
Black     18     5     23  
Asian     14     5     19  
Hispanic     6     1     7  
Other     20     11     31  
Cluster of Differentiation 4 (CD4) Cell Count  
[units: cells/mm^3]
Mean ( Full Range )
  156  
  ( 1 to 792 )  
  153  
  ( 3 to 759 )  
  155  
  ( 1 to 792 )  
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA)  
[units: copies/mL]
Geometric Mean ( Full Range )
  40519  
  ( 441 to 750000 )  
  31828  
  ( 200 to 750000 )  
  37352  
  ( 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 ]

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 (log10 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 ]
  Hide Outcome Measure 16

Measure Type Secondary
Measure Title Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count (Cells/mm^3)
Measure Description Mean change from baseline at Week 156 in CD4 Cell Count (cells/mm^3)
Time Frame Baseline and Week 156  
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.

Observed failure approach assuming baseline-carry-forward for all failures, exclude other missing values. Baseline CD4 cell count (cells/mm^3) was carried forward for participants who discontinued assigned therapy due to lack of efficacy.

Participants with virologic failure after Week 16 are treatment failures for virologic efficacy analyses.


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

Measured Values
    Raltegravir 400 mg b.i.d. + OBT     Placebo + OBT  
Number of Participants Analyzed  
[units: participants]
  207     107  
Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count (Cells/mm^3)  
[units: CD4 Cell Count (cells/mm^3)]
Mean ( 95% Confidence Interval )
  170.9  
  ( 144.4 to 197.4 )  
  71.03  
  ( 46.28 to 95.77 )  

No statistical analysis provided for Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count (Cells/mm^3)



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; 94 of 118 participants in the placebo group also received raltegravir in the open-label or OLPVF phase.


  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: Vice President, Late Stage Development Group Leader
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372
e-mail: ClinicalTrialsDisclosure@merck.com


Publications of Results:
Other Publications:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00293267     History of Changes
Other Study ID Numbers: 0518-018, 2005_096
Study First Received: February 14, 2006
Results First Received: August 18, 2009
Last Updated: October 22, 2013
Health Authority: France: Ministry of Health