Safety and Efficacy of an Investigational Drug in Human Immunodeficiency Virus (HIV)-Infected Patients Failing Current Antiretroviral Therapies (0518-005)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00105157
First received: March 8, 2005
Last updated: November 27, 2013
Last verified: November 2013
Results First Received: September 14, 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
Conditions: HIV Infections
Acquired Immunodeficiency Syndrome
Interventions: Drug: Comparator: MK0518
Drug: MK0518
Drug: Placebo

  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

Primary therapy period: 22-Apr-2005 to 09-Nov-2006

Multicenter (31) in the United States (15) and outside the United States (16)


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 >5000 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
MK0518 200 mg b.i.d. Optimized background antiretroviral therapy (OBT), if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 200 mg twice a day (b.i.d.). Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
MK0518 400 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 400 mg b.i.d.
MK0518 600 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 600 mg b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Placebo OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 matching placebo b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.

Participant Flow for 3 periods

Period 1:   Double-Blind (DB)
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo  
STARTED     44     45     45     45  
Treated     43     45     45     45  
COMPLETED     30     31     33     6  
NOT COMPLETED     14     14     12     39  
Never Treated                 1                 0                 0                 0  
Adverse Event                 2                 0                 1                 1  
Lack of Efficacy                 11                 14                 11                 38  

Period 2:   Open-Label Continuation of DB
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo  
STARTED     30     31     33     6  
COMPLETED     23     21     24     5  
NOT COMPLETED     7     10     9     1  
Adverse Event                 3                 1                 0                 0  
Lack of Efficacy                 1                 4                 3                 1  
Lost to Follow-up                 1                 1                 1                 0  
Withdrawal by Subject                 0                 1                 3                 0  
Patient did not continue in extension                 1                 0                 0                 0  
Patient moved/site stopped trial                 1                 3                 2                 0  

Period 3:   Open-Label Post Virologic Failure(OLPVF)
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo  
STARTED     11 [1]   13 [1]   11 [1]   37 [1]
COMPLETED     2     7     5     19  
NOT COMPLETED     9     6     6     18  
Adverse Event                 0                 0                 0                 1  
Lack of Efficacy                 7                 6                 5                 10  
Lost to Follow-up                 1                 0                 0                 1  
Withdrawal by Subject                 0                 0                 0                 5  
Patient moved/Site stopped trial                 1                 0                 1                 1  
[1] Number of Patients appropriate for and who consented to enter the OLPVF



  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
MK0518 200 mg b.i.d. Optimized background antiretroviral therapy (OBT), if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 200 mg twice a day (b.i.d.). Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
MK0518 400 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 400 mg b.i.d.
MK0518 600 mg b.i.d. OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 600 mg b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Placebo OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 matching placebo b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.
Total Total of all reporting groups

Baseline Measures
    MK0518 200 mg b.i.d.     MK0518 400 mg b.i.d.     MK0518 600 mg b.i.d.     Placebo     Total  
Number of Participants  
[units: participants]
  43     45     45     45     178  
Age  
[units: years]
Mean ( Full Range )
  44.0  
  ( 18 to 57 )  
  45.1  
  ( 32 to 69 )  
  43.8  
  ( 25 to 63 )  
  43.3  
  ( 29 to 59 )  
  44.1  
  ( 18 to 69 )  
Gender  
[units: participants]
         
Female     7     5     4     5     21  
Male     36     40     41     40     157  
Race/Ethnicity, Customized  
[units: participants]
         
White     36     35     32     33     136  
Black     3     5     7     5     20  
Asian     0     0     2     1     3  
Hispanic     4     5     4     5     18  
Others     0     0     0     1     1  
Cluster of Differentiation 4 (CD4) Cell Count  
[units: Cells/mm3]
Mean ( Full Range )
  244.9  
  ( 30 to 1153 )  
  220.6  
  ( 68 to 673 )  
  220.4  
  ( 30 to 663 )  
  274.0  
  ( 37 to 880 )  
  239.9  
  ( 30 to 1153 )  
Plasma HIV RNA  
[units: log10┬ácopies/mL]
Mean ( Full Range )
  4.6  
  ( 3.5 to 5.9 )  
  4.8  
  ( 3.7 to 5.9 )  
  4.7  
  ( 3.8 to 5.8 )  
  4.7  
  ( 3.6 to 5.8 )  
  4.7  
  ( 3.5 to 5.9 )  
Plasma Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA)  
[units: Copies/mL]
Mean ( Full Range )
  44642.6  
  ( 3000 to 750000 )  
  59107.9  
  ( 4770 to 750000 )  
  49064.8  
  ( 7030 to 589000 )  
  47432.6  
  ( 3630 to 611000 )  
  49841.6  
  ( 3000 to 750000 )  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 24   [ Time Frame: Baseline and Week 24 ]

2.  Secondary:   Number of Patients With Virologic Responses at Week 24   [ Time Frame: 24 weeks ]

3.  Secondary:   Change From Baseline in CD4 Cell Count at Week 24   [ Time Frame: Baseline and Week 24 ]

4.  Secondary:   Number of Patients With Clinical Adverse Experiences (CAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

5.  Secondary:   Number of Patients With Serious CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

6.  Secondary:   Number of Patients With Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

7.  Secondary:   Number of Patients With Serious Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

8.  Secondary:   Number of Patients That Died by 48 Weeks   [ Time Frame: 48 weeks ]

9.  Secondary:   Number of Patients That Discontinued With CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

10.  Secondary:   Number of Patients That Discontinued With Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

11.  Secondary:   Number of Patients That Discontinued With Serious CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

12.  Secondary:   Number of Patients That Discontinued With Serious Drug-related CAEs at 48 Weeks   [ Time Frame: 48 weeks ]

13.  Secondary:   Number of Patients With Laboratory Adverse Experiences (LAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

14.  Secondary:   Number of Patients With Drug-related LAEs at 48 Weeks   [ Time Frame: 48 weeks ]

15.  Secondary:   Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 48 Weeks   [ Time Frame: 48 weeks ]

16.  Secondary:   Number of Patients Discontinued With Drug-related LAEs at 48 Weeks   [ Time Frame: 48 weeks ]

17.  Secondary:   Number of Patients With Clinical Adverse Experiences (CAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

18.  Secondary:   Number of Patients With Serious CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

19.  Secondary:   Number of Patients With Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

20.  Secondary:   Number of Patients With Serious Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

21.  Secondary:   Number of Patients That Died by 96 Weeks   [ Time Frame: 96 weeks ]

22.  Secondary:   Number of Patients That Discontinued With CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

23.  Secondary:   Number of Patients That Discontinued With Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

24.  Secondary:   Number of Patients That Discontinued With Serious CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

25.  Secondary:   Number of Patients That Discontinued With Serious Drug-related CAEs at 96 Weeks   [ Time Frame: 96 weeks ]

26.  Secondary:   Number of Patients With Laboratory Adverse Experiences (LAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

27.  Secondary:   Number of Patients With Drug-related LAEs at 96 Weeks   [ Time Frame: 96 weeks ]

28.  Secondary:   Number of Patients Discontinued With Laboratory Adverse Experiences (LAEs) at 96 Weeks   [ Time Frame: 96 weeks ]

29.  Secondary:   Number of Patients Discontinued With Drug-related LAEs at 96 Weeks   [ Time Frame: 96 weeks ]

30.  Secondary:   Number of Patients With Clinical Adverse Experiences (CAEs) at 168 Weeks   [ Time Frame: 168 weeks ]

31.  Secondary:   Number of Patients With Serious CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

32.  Secondary:   Number of Patients With Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

33.  Secondary:   Number of Patients With Serious Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

34.  Secondary:   Number of Patients That Died by 168 Weeks   [ Time Frame: 168 weeks ]

35.  Secondary:   Number of Patients That Discontinued With CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

36.  Secondary:   Number of Patients That Discontinued With Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

37.  Secondary:   Number of Patients That Discontinued With Serious CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

38.  Secondary:   Number of Patients That Discontinued With Serious Drug-related CAEs at 168 Weeks   [ Time Frame: 168 weeks ]

39.  Secondary:   Number of Patients With Laboratory Adverse Experiences (LAEs) at 168 Weeks   [ Time Frame: 168 weeks ]

40.  Secondary:   Number of Patients With Serious LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

41.  Secondary:   Number of Patients Discontinued With Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

42.  Secondary:   Number of Patients With Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

43.  Secondary:   Number of Patients With Serious Drug-related LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

44.  Secondary:   Number of Patients Discontinued With LAEs at 168 Weeks   [ Time Frame: 168 weeks ]

45.  Post-Hoc:   Number of Patients With Virologic Responses at Week 168 in Combined Substudies   [ Time Frame: 168 weeks ]

46.  Other Pre-specified:   Change From Baseline in Plasma HIV RNA (log10 Copies/mL) at Week 168 in Combined Substudies   [ Time Frame: Baseline and Week 168 ]

47.  Other Pre-specified:   Change From Baseline in CD4 Cell Count at Week 168 in Combined Substudies   [ Time Frame: Baseline and Week 168 ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame 168 weeks: Due to a 3:1 randomization of MK0518 to placebo and more discontinuations for placebo in the double-blind phase, exposure for MK0518 and placebo differs significantly with follow-up times of 336.3 and 39.7 patient-years, respectively.
Additional Description AEs were assessed by the investigators.

Frequency Threshold
Threshold above which other adverse events are reported   2%  

Reporting Groups
  Description
MK0518 Includes patients from the MK0518 200 mg, 400 mg, and 600 mg b.i.d. dose groups. Patients who completed at least 24 weeks of double-blind therapy without virologic failure entered the open-label phase to receive open-label MK0518 400 mg b.i.d.
Placebo OBT, if possible, based on screening genotypic/phenotypic resistance and past treatment history and MK0518 matching placebo b.i.d.. Once the Phase III dose was determined, all patients were switched to the Phase III dose (400 mg b.i.d.) after completion of at least 24 weeks double-blind therapy.

Other Adverse Events
    MK0518     Placebo  
Total, other (not including serious) adverse events      
# participants affected / at risk     131/133     39/45  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     3/133 (2.26%)     2/45 (4.44%)  
Lymphadenopathy * 1    
# participants affected / at risk     11/133 (8.27%)     2/45 (4.44%)  
Splenomegaly * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Cardiac disorders      
Arrhythmia * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Cardiovascular Disorder * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Ear and labyrinth disorders      
Cerumen Impaction * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Eye disorders      
Ocular Icterus * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Vision Blurred * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Gastrointestinal disorders      
Abdominal Discomfort * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Abdominal Distension * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Abdominal Pain * 1    
# participants affected / at risk     13/133 (9.77%)     4/45 (8.89%)  
Abdominal Pain Upper * 1    
# participants affected / at risk     5/133 (3.76%)     1/45 (2.22%)  
Anal Fissure * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Anogenital Dysplasia * 1    
# participants affected / at risk     2/133 (1.50%)     1/45 (2.22%)  
Cheilitis * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Constipation * 1    
# participants affected / at risk     6/133 (4.51%)     1/45 (2.22%)  
Diarrhoea * 1    
# participants affected / at risk     29/133 (21.80%)     11/45 (24.44%)  
Dry Mouth * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Dyspepsia * 1    
# participants affected / at risk     3/133 (2.26%)     5/45 (11.11%)  
Flatulence * 1    
# participants affected / at risk     3/133 (2.26%)     2/45 (4.44%)  
Gastric Disorder * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Gastritis * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Haemorrhoids * 1    
# participants affected / at risk     3/133 (2.26%)     1/45 (2.22%)  
Hypoaesthesia Oral * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Nausea * 1    
# participants affected / at risk     21/133 (15.79%)     10/45 (22.22%)  
Periodontitis * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Tongue Ulceration * 1    
# participants affected / at risk     4/133 (3.01%)     0/45 (0.00%)  
Toothache * 1    
# participants affected / at risk     1/133 (0.75%)     2/45 (4.44%)  
Vomiting * 1    
# participants affected / at risk     11/133 (8.27%)     2/45 (4.44%)  
General disorders      
Asthenia * 1    
# participants affected / at risk     6/133 (4.51%)     3/45 (6.67%)  
Chest Discomfort * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Chest Pain * 1    
# participants affected / at risk     4/133 (3.01%)     3/45 (6.67%)  
Chills * 1    
# participants affected / at risk     2/133 (1.50%)     1/45 (2.22%)  
Drug Intolerance * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Fatigue * 1    
# participants affected / at risk     14/133 (10.53%)     4/45 (8.89%)  
Injection Site Inflammation * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Injection Site Nodule * 1    
# participants affected / at risk     3/133 (2.26%)     1/45 (2.22%)  
Injection Site Reaction * 1    
# participants affected / at risk     12/133 (9.02%)     3/45 (6.67%)  
Nodule * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Oedema Peripheral * 1    
# participants affected / at risk     7/133 (5.26%)     0/45 (0.00%)  
Pain * 1    
# participants affected / at risk     4/133 (3.01%)     2/45 (4.44%)  
Pyrexia * 1    
# participants affected / at risk     12/133 (9.02%)     1/45 (2.22%)  
Sensation Of Pressure * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Hepatobiliary disorders      
Hepatic Steatosis * 1    
# participants affected / at risk     4/133 (3.01%)     0/45 (0.00%)  
Hepatosplenomegaly * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Hyperbilirubinaemia * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Jaundice * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Immune system disorders      
Drug Hypersensitivity * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Hypersensitivity * 1    
# participants affected / at risk     2/133 (1.50%)     1/45 (2.22%)  
Infections and infestations      
Acute Tonsillitis * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Anogenital Warts * 1    
# participants affected / at risk     7/133 (5.26%)     0/45 (0.00%)  
Bronchitis * 1    
# participants affected / at risk     15/133 (11.28%)     7/45 (15.56%)  
Candidiasis * 1    
# participants affected / at risk     4/133 (3.01%)     0/45 (0.00%)  
Cellulitis * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Ear Infection * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Erysipelas * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Folliculitis * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Fungal Skin Infection * 1    
# participants affected / at risk     1/133 (0.75%)     2/45 (4.44%)  
Furuncle * 1    
# participants affected / at risk     3/133 (2.26%)     1/45 (2.22%)  
Gastroenteritis * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Genital Herpes * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Giardiasis * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Herpes Simplex * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Herpes Virus Infection * 1    
# participants affected / at risk     4/133 (3.01%)     0/45 (0.00%)  
Herpes Zoster * 1    
# participants affected / at risk     7/133 (5.26%)     1/45 (2.22%)  
Influenza * 1    
# participants affected / at risk     17/133 (12.78%)     2/45 (4.44%)  
Nasopharyngitis * 1    
# participants affected / at risk     17/133 (12.78%)     2/45 (4.44%)  
Onychomycosis * 1    
# participants affected / at risk     4/133 (3.01%)     2/45 (4.44%)  
Oral Candidiasis * 1    
# participants affected / at risk     5/133 (3.76%)     0/45 (0.00%)  
Oral Herpes * 1    
# participants affected / at risk     2/133 (1.50%)     2/45 (4.44%)  
Papilloma Viral Infection * 1    
# participants affected / at risk     2/133 (1.50%)     1/45 (2.22%)  
Pharyngitis * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Pharyngotonsillitis * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Pneumonia * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Respiratory Tract Infection * 1    
# participants affected / at risk     5/133 (3.76%)     2/45 (4.44%)  
Sinusitis * 1    
# participants affected / at risk     7/133 (5.26%)     1/45 (2.22%)  
Sinusitis Bacterial * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Skin Infection * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Syphilis * 1    
# participants affected / at risk     4/133 (3.01%)     0/45 (0.00%)  
Tooth Abscess * 1    
# participants affected / at risk     5/133 (3.76%)     0/45 (0.00%)  
Upper Respiratory Tract Infection * 1    
# participants affected / at risk     13/133 (9.77%)     4/45 (8.89%)  
Urinary Tract Infection * 1    
# participants affected / at risk     4/133 (3.01%)     0/45 (0.00%)  
Injury, poisoning and procedural complications      
Contusion * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Excoriation * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Skin Laceration * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Tibia Fracture * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Investigations      
Alanine Aminotransferase Increased * 1    
# participants affected / at risk     8/133 (6.02%)     0/45 (0.00%)  
Aspartate Aminotransferase Increased * 1    
# participants affected / at risk     9/133 (6.77%)     0/45 (0.00%)  
Blood Alkaline Phosphatase Increased * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Blood Amylase Increased * 1    
# participants affected / at risk     6/133 (4.51%)     0/45 (0.00%)  
Blood Bilirubin Increased * 1    
# participants affected / at risk     14/133 (10.53%)     2/45 (4.44%)  
Blood Cholesterol Increased * 1    
# participants affected / at risk     4/133 (3.01%)     4/45 (8.89%)  
Blood Creatine Phosphokinase Increased * 1    
# participants affected / at risk     14/133 (10.53%)     0/45 (0.00%)  
Blood Creatinine Increased * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Blood Glucose Increased * 1    
# participants affected / at risk     6/133 (4.51%)     0/45 (0.00%)  
Blood Phosphorus Decreased * 1    
# participants affected / at risk     2/133 (1.50%)     2/45 (4.44%)  
Blood Potassium Decreased * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Blood Testosterone Decreased * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Blood Triglycerides Increased * 1    
# participants affected / at risk     6/133 (4.51%)     2/45 (4.44%)  
Blood Urine Present * 1    
# participants affected / at risk     3/133 (2.26%)     2/45 (4.44%)  
Lipase Increased * 1    
# participants affected / at risk     7/133 (5.26%)     0/45 (0.00%)  
Low Density Lipoprotein Increased * 1    
# participants affected / at risk     4/133 (3.01%)     2/45 (4.44%)  
Lymphocyte Count Decreased * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Neutrophil Count Decreased * 1    
# participants affected / at risk     4/133 (3.01%)     2/45 (4.44%)  
Platelet Count Decreased * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Protein Urine Present * 1    
# participants affected / at risk     5/133 (3.76%)     1/45 (2.22%)  
Weight Decreased * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
White Blood Cell Count Decreased * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Metabolism and nutrition disorders      
Anorexia * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Decreased Appetite * 1    
# participants affected / at risk     3/133 (2.26%)     1/45 (2.22%)  
Dyslipidaemia * 1    
# participants affected / at risk     6/133 (4.51%)     0/45 (0.00%)  
Hypercholesterolaemia * 1    
# participants affected / at risk     3/133 (2.26%)     1/45 (2.22%)  
Musculoskeletal and connective tissue disorders      
Arthralgia * 1    
# participants affected / at risk     7/133 (5.26%)     3/45 (6.67%)  
Arthritis * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Back Pain * 1    
# participants affected / at risk     10/133 (7.52%)     1/45 (2.22%)  
Muscle Hypertrophy * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Muscle Spasms * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Musculoskeletal Pain * 1    
# participants affected / at risk     7/133 (5.26%)     0/45 (0.00%)  
Myalgia * 1    
# participants affected / at risk     8/133 (6.02%)     0/45 (0.00%)  
Neck Pain * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Pain In Extremity * 1    
# participants affected / at risk     10/133 (7.52%)     2/45 (4.44%)  
Tendonitis * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Tenosynovitis * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Skin Papilloma * 1    
# participants affected / at risk     3/133 (2.26%)     1/45 (2.22%)  
Nervous system disorders      
Dizziness * 1    
# participants affected / at risk     5/133 (3.76%)     0/45 (0.00%)  
Dysgeusia * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Dysphasia * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Facial Palsy * 1    
# participants affected / at risk     0/133 (0.00%)     2/45 (4.44%)  
Headache * 1    
# participants affected / at risk     21/133 (15.79%)     5/45 (11.11%)  
Hemicephalalgia * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Hypoaesthesia * 1    
# participants affected / at risk     3/133 (2.26%)     1/45 (2.22%)  
Migraine * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Neuropathy Peripheral * 1    
# participants affected / at risk     5/133 (3.76%)     2/45 (4.44%)  
Paraesthesia * 1    
# participants affected / at risk     8/133 (6.02%)     0/45 (0.00%)  
Syncope * 1    
# participants affected / at risk     2/133 (1.50%)     1/45 (2.22%)  
Psychiatric disorders      
Anxiety * 1    
# participants affected / at risk     4/133 (3.01%)     2/45 (4.44%)  
Depression * 1    
# participants affected / at risk     10/133 (7.52%)     1/45 (2.22%)  
Insomnia * 1    
# participants affected / at risk     12/133 (9.02%)     2/45 (4.44%)  
Sleep Disorder * 1    
# participants affected / at risk     2/133 (1.50%)     1/45 (2.22%)  
Renal and urinary disorders      
Dysuria * 1    
# participants affected / at risk     3/133 (2.26%)     2/45 (4.44%)  
Nephrolithiasis * 1    
# participants affected / at risk     2/133 (1.50%)     1/45 (2.22%)  
Renal Cyst * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Reproductive system and breast disorders      
Benign Prostatic Hyperplasia * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Erectile Dysfunction * 1    
# participants affected / at risk     5/133 (3.76%)     0/45 (0.00%)  
Pelvic Pain * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Prostatitis * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Cough * 1    
# participants affected / at risk     23/133 (17.29%)     1/45 (2.22%)  
Dyspnoea * 1    
# participants affected / at risk     6/133 (4.51%)     0/45 (0.00%)  
Oropharyngeal Pain * 1    
# participants affected / at risk     4/133 (3.01%)     3/45 (6.67%)  
Paranasal Sinus Hypersecretion * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Productive Cough * 1    
# participants affected / at risk     5/133 (3.76%)     0/45 (0.00%)  
Rhinitis Allergic * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Rhinorrhoea * 1    
# participants affected / at risk     0/133 (0.00%)     2/45 (4.44%)  
Sinus Congestion * 1    
# participants affected / at risk     3/133 (2.26%)     2/45 (4.44%)  
Sneezing * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Skin and subcutaneous tissue disorders      
Alopecia * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Dry Skin * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Dyshidrosis * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Eczema * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Erythema * 1    
# participants affected / at risk     4/133 (3.01%)     0/45 (0.00%)  
Facial Wasting * 1    
# participants affected / at risk     4/133 (3.01%)     0/45 (0.00%)  
Lipodystrophy Acquired * 1    
# participants affected / at risk     6/133 (4.51%)     0/45 (0.00%)  
Night Sweats * 1    
# participants affected / at risk     2/133 (1.50%)     3/45 (6.67%)  
Pruritus * 1    
# participants affected / at risk     9/133 (6.77%)     1/45 (2.22%)  
Rash * 1    
# participants affected / at risk     9/133 (6.77%)     1/45 (2.22%)  
Rash Macular * 1    
# participants affected / at risk     1/133 (0.75%)     1/45 (2.22%)  
Rash Papular * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Seborrhoeic Dermatitis * 1    
# participants affected / at risk     0/133 (0.00%)     1/45 (2.22%)  
Skin Lesion * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Skin Nodule * 1    
# participants affected / at risk     2/133 (1.50%)     1/45 (2.22%)  
Subcutaneous Nodule * 1    
# participants affected / at risk     4/133 (3.01%)     1/45 (2.22%)  
Vascular disorders      
Hyperaemia * 1    
# participants affected / at risk     3/133 (2.26%)     0/45 (0.00%)  
Hypertension * 1    
# participants affected / at risk     13/133 (9.77%)     0/45 (0.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA Version 12.0



  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
Due to a 3:1 randomization of MK-0518 to placebo and more discontinuations for placebo in the doubleblind phase, exposure for MK-0518 and placebo differs significantly with follow-up times of 336.3 and 39.7 patient-years, respectively.


  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: Executive Vice President, Clinical and Quantitative Sciences
Organization: Merck Sharp & Dohme Corp
phone: 1-800-672-6372


Publications:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00105157     History of Changes
Other Study ID Numbers: 0518-005, MK0518-005, 2005_007
Study First Received: March 8, 2005
Results First Received: September 14, 2009
Last Updated: November 27, 2013
Health Authority: United States: Food and Drug Administration