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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: September 4, 2015
Last verified: September 2015
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 
Overall Participants Analyzed 
[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
  Show All Outcome Measures

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 ]

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
  Hide Other Adverse Events

Time Frame 240 Weeks
Additional Description 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.

Frequency Threshold
Threshold above which other adverse events are reported   5  

Reporting Groups
  Description
Raltegravir 400 mg b.i.d Plus OBT

Includes all participants initially randomized to raltegravir, including those without virologic failure who

continued into the open-label phase at Week 156 and those who entered the OLPVF phase due to virologic failure. During either open-label phase up to Week 240, these participants continued to receive raltegravir 400 mg b.i.d. plus OBT.

Placebo Plus OBT Includes all participants initially randomized to placebo, including those without virologic failure who continued into the open-label phase at Week 156 and those who entered the OLPVF phase due to virologic failure. During either open-label phase up to Week 240, these participants continued to receive raltegravir 400 mg b.i.d. plus OBT.

Other Adverse Events
    Raltegravir 400 mg b.i.d Plus OBT   Placebo Plus OBT
Total, other (not including serious) adverse events     
# participants affected / at risk   206/232 (88.79%)   104/118 (88.14%) 
Blood and lymphatic system disorders     
Anaemia † 1     
# participants affected / at risk   9/232 (3.88%)   7/118 (5.93%) 
# events   12   13 
Lymphadenopathy † 1     
# participants affected / at risk   19/232 (8.19%)   5/118 (4.24%) 
# events   19   8 
Gastrointestinal disorders     
Abdominal pain † 1     
# participants affected / at risk   15/232 (6.47%)   11/118 (9.32%) 
# events   16   12 
Diarrhoea † 1     
# participants affected / at risk   74/232 (31.90%)   34/118 (28.81%) 
# events   110   70 
Gastritis † 1     
# participants affected / at risk   8/232 (3.45%)   7/118 (5.93%) 
# events   8   8 
Haemorrhoids † 1     
# participants affected / at risk   12/232 (5.17%)   2/118 (1.69%) 
# events   12   2 
Nausea † 1     
# participants affected / at risk   30/232 (12.93%)   20/118 (16.95%) 
# events   38   25 
Vomiting † 1     
# participants affected / at risk   18/232 (7.76%)   17/118 (14.41%) 
# events   26   25 
General disorders     
Asthenia † 1     
# participants affected / at risk   15/232 (6.47%)   11/118 (9.32%) 
# events   16   11 
Fatigue † 1     
# participants affected / at risk   18/232 (7.76%)   6/118 (5.08%) 
# events   18   9 
Injection site reaction † 1     
# participants affected / at risk   18/232 (7.76%)   14/118 (11.86%) 
# events   19   16 
Pyrexia † 1     
# participants affected / at risk   28/232 (12.07%)   18/118 (15.25%) 
# events   35   23 
Infections and infestations     
Anogenital warts † 1     
# participants affected / at risk   11/232 (4.74%)   6/118 (5.08%) 
# events   14   7 
Bronchitis † 1     
# participants affected / at risk   42/232 (18.10%)   16/118 (13.56%) 
# events   71   23 
Gastroenteritis † 1     
# participants affected / at risk   22/232 (9.48%)   3/118 (2.54%) 
# events   28   4 
Genital herpes † 1     
# participants affected / at risk   10/232 (4.31%)   9/118 (7.63%) 
# events   11   12 
Herpes simplex † 1     
# participants affected / at risk   12/232 (5.17%)   3/118 (2.54%) 
# events   13   6 
Herpes zoster † 1     
# participants affected / at risk   20/232 (8.62%)   7/118 (5.93%) 
# events   23   10 
Influenza † 1     
# participants affected / at risk   25/232 (10.78%)   8/118 (6.78%) 
# events   28   11 
Nasopharyngitis † 1     
# participants affected / at risk   58/232 (25.00%)   21/118 (17.80%) 
# events   96   51 
Oral candidiasis † 1     
# participants affected / at risk   11/232 (4.74%)   15/118 (12.71%) 
# events   14   20 
Pharyngitis † 1     
# participants affected / at risk   15/232 (6.47%)   8/118 (6.78%) 
# events   24   11 
Pneumonia † 1     
# participants affected / at risk   9/232 (3.88%)   9/118 (7.63%) 
# events   12   11 
Respiratory tract infection † 1     
# participants affected / at risk   19/232 (8.19%)   3/118 (2.54%) 
# events   21   5 
Sinusitis † 1     
# participants affected / at risk   11/232 (4.74%)   6/118 (5.08%) 
# events   15   13 
Upper respiratory tract infection † 1     
# participants affected / at risk   20/232 (8.62%)   7/118 (5.93%) 
# events   35   15 
Urinary tract infection † 1     
# participants affected / at risk   14/232 (6.03%)   6/118 (5.08%) 
# events   17   8 
Investigations     
Alanine aminotransferase increased † 1     
# participants affected / at risk   24/232 (10.34%)   9/118 (7.63%) 
# events   40   19 
Aspartate aminotransferase increased † 1     
# participants affected / at risk   24/232 (10.34%)   8/118 (6.78%) 
# events   30   18 
Blood cholesterol increased † 1     
# participants affected / at risk   28/232 (12.07%)   9/118 (7.63%) 
# events   44   20 
Blood triglycerides increased † 1     
# participants affected / at risk   22/232 (9.48%)   11/118 (9.32%) 
# events   30   14 
Weight decreased † 1     
# participants affected / at risk   6/232 (2.59%)   7/118 (5.93%) 
# events   8   7 
Metabolism and nutrition disorders     
Decreased appetite † 1     
# participants affected / at risk   12/232 (5.17%)   6/118 (5.08%) 
# events   13   6 
Diabetes mellitus † 1     
# participants affected / at risk   6/232 (2.59%)   6/118 (5.08%) 
# events   7   6 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   14/232 (6.03%)   7/118 (5.93%) 
# events   15   8 
Back pain † 1     
# participants affected / at risk   26/232 (11.21%)   10/118 (8.47%) 
# events   33   14 
Muscle spasms † 1     
# participants affected / at risk   12/232 (5.17%)   7/118 (5.93%) 
# events   15   7 
Myalgia † 1     
# participants affected / at risk   9/232 (3.88%)   8/118 (6.78%) 
# events   9   9 
Pain in extremity † 1     
# participants affected / at risk   12/232 (5.17%)   6/118 (5.08%) 
# events   16   6 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin papilloma † 1     
# participants affected / at risk   16/232 (6.90%)   6/118 (5.08%) 
# events   20   8 
Nervous system disorders     
Dizziness † 1     
# participants affected / at risk   14/232 (6.03%)   2/118 (1.69%) 
# events   15   2 
Headache † 1     
# participants affected / at risk   28/232 (12.07%)   24/118 (20.34%) 
# events   38   29 
Psychiatric disorders     
Depression † 1     
# participants affected / at risk   13/232 (5.60%)   9/118 (7.63%) 
# events   14   10 
Insomnia † 1     
# participants affected / at risk   24/232 (10.34%)   12/118 (10.17%) 
# events   24   14 
Respiratory, thoracic and mediastinal disorders     
Cough † 1     
# participants affected / at risk   20/232 (8.62%)   11/118 (9.32%) 
# events   24   14 
Skin and subcutaneous tissue disorders     
Eczema † 1     
# participants affected / at risk   6/232 (2.59%)   7/118 (5.93%) 
# events   7   7 
Lipodystrophy acquired † 1     
# participants affected / at risk   11/232 (4.74%)   6/118 (5.08%) 
# events   11   6 
Pruritus † 1     
# participants affected / at risk   16/232 (6.90%)   6/118 (5.08%) 
# events   20   6 
Rash † 1     
# participants affected / at risk   20/232 (8.62%)   7/118 (5.93%) 
# events   25   12 
Vascular disorders     
Hypertension † 1     
# participants affected / at risk   32/232 (13.79%)   12/118 (10.17%) 
# events   32   12 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 14.0



  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: Senior Vice President, Global Clinical Development
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: September 4, 2015
Health Authority: France: Ministry of Health