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

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: July 16, 2015
Last verified: July 2015
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 
Overall Participants Analyzed 
[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
  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 (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
  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; 83 of 119 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   214/230 (93.04%)   111/119 (93.28%) 
Blood and lymphatic system disorders     
Anaemia † 1     
# participants affected / at risk   9/230 (3.91%)   9/119 (7.56%) 
# events   9   10 
Lymphadenopathy † 1     
# participants affected / at risk   19/230 (8.26%)   4/119 (3.36%) 
# events   24   4 
Eye disorders     
Conjunctivitis † 1     
# participants affected / at risk   17/230 (7.39%)   2/119 (1.68%) 
# events   18   2 
Gastrointestinal disorders     
Abdominal distension † 1     
# participants affected / at risk   15/230 (6.52%)   6/119 (5.04%) 
# events   18   6 
Abdominal pain † 1     
# participants affected / at risk   25/230 (10.87%)   7/119 (5.88%) 
# events   31   8 
Abdominal pain upper † 1     
# participants affected / at risk   17/230 (7.39%)   11/119 (9.24%) 
# events   19   11 
Constipation † 1     
# participants affected / at risk   15/230 (6.52%)   5/119 (4.20%) 
# events   19   6 
Diarrhoea † 1     
# participants affected / at risk   75/230 (32.61%)   35/119 (29.41%) 
# events   108   41 
Dry mouth † 1     
# participants affected / at risk   2/230 (0.87%)   7/119 (5.88%) 
# events   2   7 
Flatulence † 1     
# participants affected / at risk   17/230 (7.39%)   5/119 (4.20%) 
# events   20   7 
Haemorrhoids † 1     
# participants affected / at risk   8/230 (3.48%)   6/119 (5.04%) 
# events   8   6 
Nausea † 1     
# participants affected / at risk   41/230 (17.83%)   30/119 (25.21%) 
# events   57   40 
Vomiting † 1     
# participants affected / at risk   25/230 (10.87%)   17/119 (14.29%) 
# events   41   19 
General disorders     
Asthenia † 1     
# participants affected / at risk   12/230 (5.22%)   2/119 (1.68%) 
# events   13   2 
Chest pain † 1     
# participants affected / at risk   13/230 (5.65%)   4/119 (3.36%) 
# events   15   4 
Fatigue † 1     
# participants affected / at risk   45/230 (19.57%)   18/119 (15.13%) 
# events   57   22 
Injection site reaction † 1     
# participants affected / at risk   35/230 (15.22%)   14/119 (11.76%) 
# events   41   16 
Oedema peripheral † 1     
# participants affected / at risk   12/230 (5.22%)   9/119 (7.56%) 
# events   13   10 
Pyrexia † 1     
# participants affected / at risk   29/230 (12.61%)   24/119 (20.17%) 
# events   32   35 
Infections and infestations     
Anogenital warts † 1     
# participants affected / at risk   12/230 (5.22%)   4/119 (3.36%) 
# events   15   4 
Bronchitis † 1     
# participants affected / at risk   34/230 (14.78%)   15/119 (12.61%) 
# events   44   18 
Cellulitis † 1     
# participants affected / at risk   11/230 (4.78%)   7/119 (5.88%) 
# events   15   7 
Folliculitis † 1     
# participants affected / at risk   12/230 (5.22%)   4/119 (3.36%) 
# events   14   4 
Furuncle † 1     
# participants affected / at risk   4/230 (1.74%)   6/119 (5.04%) 
# events   4   6 
Gastroenteritis † 1     
# participants affected / at risk   13/230 (5.65%)   6/119 (5.04%) 
# events   14   6 
Herpes zoster † 1     
# participants affected / at risk   27/230 (11.74%)   5/119 (4.20%) 
# events   30   5 
Influenza † 1     
# participants affected / at risk   17/230 (7.39%)   9/119 (7.56%) 
# events   21   14 
Nasopharyngitis † 1     
# participants affected / at risk   29/230 (12.61%)   15/119 (12.61%) 
# events   50   20 
Onychomycosis † 1     
# participants affected / at risk   8/230 (3.48%)   7/119 (5.88%) 
# events   9   8 
Oral candidiasis † 1     
# participants affected / at risk   12/230 (5.22%)   11/119 (9.24%) 
# events   12   12 
Pneumonia † 1     
# participants affected / at risk   14/230 (6.09%)   10/119 (8.40%) 
# events   19   14 
Sinusitis † 1     
# participants affected / at risk   35/230 (15.22%)   15/119 (12.61%) 
# events   50   18 
Upper respiratory tract infection † 1     
# participants affected / at risk   76/230 (33.04%)   29/119 (24.37%) 
# events   114   47 
Urinary tract infection † 1     
# participants affected / at risk   11/230 (4.78%)   11/119 (9.24%) 
# events   12   18 
Investigations     
Alanine aminotransferase increased † 1     
# participants affected / at risk   18/230 (7.83%)   9/119 (7.56%) 
# events   29   11 
Aspartate aminotransferase increased † 1     
# participants affected / at risk   20/230 (8.70%)   9/119 (7.56%) 
# events   27   12 
Blood bilirubin increased † 1     
# participants affected / at risk   6/230 (2.61%)   6/119 (5.04%) 
# events   7   10 
Blood cholesterol increased † 1     
# participants affected / at risk   10/230 (4.35%)   9/119 (7.56%) 
# events   11   11 
Blood creatine phosphokinase increased † 1     
# participants affected / at risk   21/230 (9.13%)   8/119 (6.72%) 
# events   24   8 
Blood creatinine increased † 1     
# participants affected / at risk   18/230 (7.83%)   11/119 (9.24%) 
# events   37   17 
Blood glucose increased † 1     
# participants affected / at risk   13/230 (5.65%)   6/119 (5.04%) 
# events   28   7 
Blood phosphorus decreased † 1     
# participants affected / at risk   3/230 (1.30%)   6/119 (5.04%) 
# events   3   8 
Blood triglycerides increased † 1     
# participants affected / at risk   22/230 (9.57%)   14/119 (11.76%) 
# events   30   15 
Weight decreased † 1     
# participants affected / at risk   14/230 (6.09%)   8/119 (6.72%) 
# events   15   9 
Metabolism and nutrition disorders     
Decreased appetite † 1     
# participants affected / at risk   13/230 (5.65%)   10/119 (8.40%) 
# events   16   10 
Hyperlipidaemia † 1     
# participants affected / at risk   12/230 (5.22%)   1/119 (0.84%) 
# events   12   1 
Musculoskeletal and connective tissue disorders     
Arthralgia † 1     
# participants affected / at risk   24/230 (10.43%)   15/119 (12.61%) 
# events   32   18 
Back pain † 1     
# participants affected / at risk   26/230 (11.30%)   14/119 (11.76%) 
# events   27   17 
Musculoskeletal pain † 1     
# participants affected / at risk   16/230 (6.96%)   5/119 (4.20%) 
# events   17   6 
Myalgia † 1     
# participants affected / at risk   14/230 (6.09%)   13/119 (10.92%) 
# events   16   19 
Pain in extremity † 1     
# participants affected / at risk   27/230 (11.74%)   9/119 (7.56%) 
# events   35   12 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Skin papilloma † 1     
# participants affected / at risk   21/230 (9.13%)   8/119 (6.72%) 
# events   23   10 
Nervous system disorders     
Dizziness † 1     
# participants affected / at risk   22/230 (9.57%)   10/119 (8.40%) 
# events   27   13 
Headache † 1     
# participants affected / at risk   39/230 (16.96%)   19/119 (15.97%) 
# events   62   24 
Hypoaesthesia † 1     
# participants affected / at risk   7/230 (3.04%)   8/119 (6.72%) 
# events   10   10 
Neuropathy peripheral † 1     
# participants affected / at risk   15/230 (6.52%)   9/119 (7.56%) 
# events   19   11 
Paraesthesia † 1     
# participants affected / at risk   10/230 (4.35%)   6/119 (5.04%) 
# events   12   7 
Psychiatric disorders     
Anxiety † 1     
# participants affected / at risk   7/230 (3.04%)   13/119 (10.92%) 
# events   7   14 
Depression † 1     
# participants affected / at risk   15/230 (6.52%)   11/119 (9.24%) 
# events   17   12 
Insomnia † 1     
# participants affected / at risk   22/230 (9.57%)   11/119 (9.24%) 
# events   27   12 
Respiratory, thoracic and mediastinal disorders     
Cough † 1     
# participants affected / at risk   26/230 (11.30%)   21/119 (17.65%) 
# events   32   29 
Dyspnoea † 1     
# participants affected / at risk   4/230 (1.74%)   6/119 (5.04%) 
# events   5   6 
Oropharyngeal pain † 1     
# participants affected / at risk   17/230 (7.39%)   7/119 (5.88%) 
# events   18   8 
Sinus congestion † 1     
# participants affected / at risk   6/230 (2.61%)   8/119 (6.72%) 
# events   7   8 
Skin and subcutaneous tissue disorders     
Night sweats † 1     
# participants affected / at risk   11/230 (4.78%)   6/119 (5.04%) 
# events   15   7 
Pruritus † 1     
# participants affected / at risk   7/230 (3.04%)   7/119 (5.88%) 
# events   8   8 
Rash † 1     
# participants affected / at risk   30/230 (13.04%)   12/119 (10.08%) 
# events   36   17 
Vascular disorders     
Hypertension † 1     
# participants affected / at risk   21/230 (9.13%)   5/119 (4.20%) 
# events   21   6 
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; 83 of 119 participants in the placebo group also received raltegravir in the open-label or OLPVF phase.


  More Information