Safety and Efficacy of SCH 503034 in Previously Untreated Subjects With Chronic Hepatitis C Infected With Genotype 1 (Study P03523)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00423670
First received: January 17, 2007
Last updated: March 17, 2014
Last verified: March 2014
Results First Received: May 13, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Chronic Hepatitis C
Interventions: Drug: boceprevir (SCH 503034)
Drug: peginterferon-alfa 2b (PegIntron)
Drug: ribavirin
Drug: ribavirin (low-dose)

  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

765 participants were screened in the study, 598 were randomized of which 3 participants were not

treated (Arm 1-7). Participants were assigned to Part I (with standard dosing for ribavirin) or Part II (to explore low-dose ribavirin). All participants that completed or discontinued treatment were scheduled to enter follow-up phase per protocol.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants in Arm 1 (Part I) who had detectable Hepatitis C Virus-ribonucleic acid (HCV-RNA) at Treatment Week (TW) 24 were offered boceprevir in addition to PegIntron and ribavirin for an additional 24 weeks of treatment, and switched to a new arm, Arm 8.

Reporting Groups
  Description
Arm 1. PEG +RBV for 48 Wks (Part I)

PegIntron (1.5 μg/kg, once weekly [QW]) plus ribavirin (800 to 1400 mg/day) for 48 weeks.

• Participants with detectable HCV-RNA levels after 24 weeks of treatment had the option of crossing over to receive 24 weeks of PegIntron, ribavirin, and boceprevir (800 mg, thrice a day [TID]) for 24 additional weeks. Total treatment duration was up to 54 weeks.

Arm 2. PEG + RBV + BOC for 28 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead-in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead-in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I) Participants that started in Arm 1 and had detectable HCV-RNA levels after 24 weeks of treatment had the option of receiving boceprevir (800 mg TID) with PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day). Participants that took the option of crossing over to receive 24 weeks of PegIntron, ribavirin, and boceprevir (800 mg TID) for 24 additional weeks constitute Arm 8. The total treatment duration was up to 54 weeks.

Participant Flow for 2 periods

Period 1:   Treatment Period
    Arm 1. PEG +RBV for 48 Wks (Part I)     Arm 2. PEG + RBV + BOC for 28 Wks (Part I)     Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)     Arm 4. PEG +RBV + BOC for 48 Wks (Part I)     Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I)     Arm 6. PEG + RBV + BOC for 48 Wks (Part II)     Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)     Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I)  
STARTED     104     107     103     103     103     16     59     36 [1]
COMPLETED     52     77     76     63     76     8     28     15  
NOT COMPLETED     52     30     27     40     27     8     31     21  
Switched to Arm 8 at TW 24                 36                 0                 0                 0                 0                 0                 0                 0  
Adverse Event                 8                 12                 15                 20                 9                 4                 7                 2  
Protocol-defined clinical event                 0                 7                 4                 12                 5                 4                 16                 15  
Lost to Follow-up                 2                 1                 3                 1                 6                 0                 3                 1  
Subject withdrew (not treatment related)                 3                 9                 4                 4                 5                 0                 3                 0  
Investigator decision                 0                 0                 0                 0                 0                 0                 0                 1  
Non-compliance with protocol                 3                 1                 1                 3                 2                 0                 2                 2  
[1] Arm 8 were Arm 1 participants that were positive for HCV-RNA at TW 24 and had the option to switch.

Period 2:   Follow-up Period
    Arm 1. PEG +RBV for 48 Wks (Part I)     Arm 2. PEG + RBV + BOC for 28 Wks (Part I)     Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)     Arm 4. PEG +RBV + BOC for 48 Wks (Part I)     Arm 5. PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I)     Arm 6. PEG + RBV + BOC for 48 Wks (Part II)     Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)     Arm 8. PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I)  
STARTED     97     100     96     96     91     14     50     35  
COMPLETED     94     84     85     91     89     14     41     32  
NOT COMPLETED     3     16     11     5     2     0     9     3  
Lost to Follow-up                 0                 12                 8                 3                 1                 0                 5                 0  
Subject withdrew (not treatment related)                 1                 4                 2                 1                 1                 0                 1                 1  
Non-compliance with protocol                 2                 0                 1                 1                 0                 0                 3                 2  



  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
Arm 1. PEG +RBV for 48 Wks (Part I)

PegIntron (1.5 μg/kg QW) plus ribavirin (800 to 1400 mg/day) for 48 weeks.

• Participants with detectable HCV-RNA levels after 24 weeks of treatment had to receive 24 weeks of PegIntron, ribavirin and boceprevir (800 mg TID) for 24 additional weeks. Total treatment duration was up to 54 weeks.

Arm 2. PEG + RBV + BOC for 28 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
Arm 4. PEG +RBV + BOC for 48 Wks (Part I) Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I) PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
Arm 6. PEG + RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II) PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
Total Total of all reporting groups

Baseline Measures
    Arm 1. PEG +RBV for 48 Wks (Part I)     Arm 2. PEG + RBV + BOC for 28 Wks (Part I)     Arm 3. PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)     Arm 4. PEG +RBV + BOC for 48 Wks (Part I)     Arm 5. PEG + RBV+ BOC (From Wk 4) for 44 Wks (Part I)     Arm 6. PEG + RBV + BOC for 48 Wks (Part II)     Arm 7. PEG +Low-dose RBV + BOC for 48 Wks (Part II)     Total  
Number of Participants  
[units: participants]
  104     107     103     103     103     16     59     595  
Age [1]
[units: years]
Mean ± Standard Deviation
  48.3  ± 6.9     46.4  ± 8.0     47.7  ± 7.4     46.7  ± 8.8     47.6  ± 8.3     50.3  ± 8.5     48.7  ± 5.8     47.5  ± 7.7  
Gender [2]
[units: participants]
               
Female     34     44     52     40     45     7     18     240  
Male     70     63     51     63     58     9     41     355  
[1] Overall age characteristics were displayed for Arm 1 through Arm 7. Participants from Arm 1 (Part I) who had detectable HCV-RNA at TW 24, had the option to switch to a new arm, Arm 8.
[2] Overall gender characteristics were displayed for Arm 1 through Arm 7. Participants from Arm 1 (Part I) who had detectable HCV-RNA TW 24, had the option to switch to a new arm, Arm 8.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With Sustained Virologic Response (SVR)   [ Time Frame: From follow-up week (FW) 24 up to end of follow-up (EOF) ]

2.  Secondary:   Number of Participants With SVR Based on a 4-week lead-in Treatment With PegIntron and Ribavirin   [ Time Frame: From FW 24 up to EOF ]

3.  Secondary:   Number of Participants With SVR Based on Duration of Boceprevir Treatment   [ Time Frame: From FW 24 up to EOF ]

4.  Secondary:   Number of Participants Negative for HCV-RNA at FW 12   [ Time Frame: At FW 12 ]

5.  Secondary:   Number of Participants Negative for HCV-RNA at 72 Weeks Post Randomization   [ Time Frame: 72 weeks post randomization ]

6.  Secondary:   Number of Participants With an Early Virologic Response (EVR) That Achieved SVR   [ Time Frame: At TW 12, and at FW 24 up to EOF ]

7.  Secondary:   Number of Participants With a Virologic Response at Follow-up Week 12 That Achieved SVR   [ Time Frame: At FW 12 and FW 24 up to EOF ]

8.  Secondary:   Number of Participants With a Virologic Response at 72 Weeks Post Randomization That Achieved SVR   [ Time Frame: At FW 24 up to EOF and at 72 weeks post randomization ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description No text entered.

Frequency Threshold
Threshold above which other adverse events are reported   5%  

Reporting Groups
  Description
PEG +RBV for 48 Wks (Part I)

Arm 1. PegIntron (1.5 μg/kg, once weekly [QW]) plus ribavirin (800 to 1400 mg/day) for 48 weeks.

• Participants with detectable HCV-RNA levels after 24 weeks of treatment had the option of crossing over to receive 24 weeks of PegIntron, ribavirin, and boceprevir (800 mg, thrice a day [TID]) for 24 additional weeks. Total treatment duration was up to 54 weeks.

Adverse events for 36 participants after they crossed over to Arm 8 are not included.

PEG + RBV + BOC for 28 Wks (Part I) Arm 2. Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 28 weeks.
PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I) Arm 3. PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead-in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 24 weeks.
PEG +RBV + BOC for 48 Wks (Part I) Arm 4. Boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 48 weeks.
PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I) Arm 5. PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for 4 weeks lead-in followed by boceprevir (800 mg TID) plus PegIntron (1.5 μg/kg QW) and ribavirin (800 to 1400 mg/day) for up to 44 weeks.
PEG + RBV + BOC for 48 Wks (Part II) Arm 6. PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
PEG +Low-dose RBV + BOC for 48 Wks (Part II) Arm 7. PegIntron (1.5 μg/kg QW), ribavirin (400 to 1000 mg/day) and boceprevir (800 mg TID) for up to 48 weeks.
PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I) Arm 8. Participants that started in Arm 1 and had detectable HCV-RNA levels after 24 weeks of treatment had the option of receiving boceprevir (800 mg TID) with PegIntron (1.5 μg/kg QW), ribavirin (800 to 1400 mg/day). Participants that took the option of crossing over to receive 24 weeks of PegIntron, ribavirin, and boceprevir (800 mg TID) for 24 additional weeks constitute Arm 8. The total treatment duration was up to 54 weeks.

Other Adverse Events
    PEG +RBV for 48 Wks (Part I)     PEG + RBV + BOC for 28 Wks (Part I)     PEG + RBV + BOC (From Wk 4) for 24 Wks (Part I)     PEG +RBV + BOC for 48 Wks (Part I)     PEG + RBV + BOC (From Wk 4) for 44 Wks (Part I)     PEG + RBV + BOC for 48 Wks (Part II)     PEG +Low-dose RBV + BOC for 48 Wks (Part II)     PEG + RBV + BOC (From Wk 24) for 48 Wks (Part I)  
Total, other (not including serious) adverse events                  
# participants affected / at risk     102/104     106/107     102/103     103/103     102/103     16/16     59/59     29/36  
Blood and lymphatic system disorders                  
ANAEMIA                
# participants affected / at risk     35/104 (33.65%)     59/107 (55.14%)     55/103 (53.40%)     54/103 (52.43%)     58/103 (56.31%)     10/16 (62.50%)     14/59 (23.73%)     13/36 (36.11%)  
# events     55     96     80     79     88     22     39     13  
LEUKOPENIA                
# participants affected / at risk     6/104 (5.77%)     7/107 (6.54%)     5/103 (4.85%)     5/103 (4.85%)     8/103 (7.77%)     1/16 (6.25%)     9/59 (15.25%)     1/36 (2.78%)  
# events     15     37     12     9     12     7     58     2  
LYMPHADENOPATHY                
# participants affected / at risk     0/104 (0.00%)     2/107 (1.87%)     0/103 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     2     0     0     1     1     0     0  
NEUTROPENIA                
# participants affected / at risk     12/104 (11.54%)     23/107 (21.50%)     16/103 (15.53%)     26/103 (25.24%)     31/103 (30.10%)     2/16 (12.50%)     19/59 (32.20%)     8/36 (22.22%)  
# events     32     82     30     50     71     11     88     9  
PANCYTOPENIA                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     1/103 (0.97%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     1     0     0     1     0     0  
THROMBOCYTOPENIA                
# participants affected / at risk     0/104 (0.00%)     5/107 (4.67%)     1/103 (0.97%)     1/103 (0.97%)     6/103 (5.83%)     1/16 (6.25%)     5/59 (8.47%)     3/36 (8.33%)  
# events     0     7     1     1     9     1     26     3  
Cardiac disorders                  
PALPITATIONS                
# participants affected / at risk     2/104 (1.92%)     1/107 (0.93%)     2/103 (1.94%)     3/103 (2.91%)     0/103 (0.00%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     3     1     2     3     0     1     1     0  
Ear and labyrinth disorders                  
TINNITUS                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     3/103 (2.91%)     7/103 (6.80%)     3/103 (2.91%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     1     0     3     7     3     1     0     0  
Endocrine disorders                  
HYPOTHYROIDISM                
# participants affected / at risk     6/104 (5.77%)     2/107 (1.87%)     3/103 (2.91%)     1/103 (0.97%)     5/103 (4.85%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     6     2     3     1     9     1     0     0  
Eye disorders                  
CONJUNCTIVAL DISCOLOURATION                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     2/103 (1.94%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     0     2     1     0     0  
CONJUNCTIVITIS                
# participants affected / at risk     1/104 (0.96%)     1/107 (0.93%)     1/103 (0.97%)     1/103 (0.97%)     3/103 (2.91%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     1     1     1     1     3     1     0     0  
DRY EYE                
# participants affected / at risk     4/104 (3.85%)     1/107 (0.93%)     3/103 (2.91%)     6/103 (5.83%)     4/103 (3.88%)     2/16 (12.50%)     5/59 (8.47%)     0/36 (0.00%)  
# events     4     1     4     6     4     2     5     0  
EYE IRRITATION                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     1/103 (0.97%)     0/103 (0.00%)     1/103 (0.97%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     0     0     1     0     1     1     1     0  
RETINAL HAEMORRHAGE                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     1     0     0     0     1     0     0  
RETINOPATHY                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     0     0     1     0     0  
VISION BLURRED                
# participants affected / at risk     7/104 (6.73%)     6/107 (5.61%)     2/103 (1.94%)     8/103 (7.77%)     7/103 (6.80%)     2/16 (12.50%)     3/59 (5.08%)     0/36 (0.00%)  
# events     7     6     2     8     7     2     3     0  
VISUAL IMPAIRMENT                
# participants affected / at risk     2/104 (1.92%)     1/107 (0.93%)     5/103 (4.85%)     7/103 (6.80%)     3/103 (2.91%)     0/16 (0.00%)     2/59 (3.39%)     0/36 (0.00%)  
# events     2     1     5     7     3     0     2     0  
Gastrointestinal disorders                  
ABDOMINAL DISCOMFORT                
# participants affected / at risk     2/104 (1.92%)     0/107 (0.00%)     1/103 (0.97%)     1/103 (0.97%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     2     0     1     1     1     1     0     0  
ABDOMINAL DISTENSION                
# participants affected / at risk     1/104 (0.96%)     1/107 (0.93%)     0/103 (0.00%)     2/103 (1.94%)     3/103 (2.91%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     1     1     0     2     3     1     0     0  
ABDOMINAL PAIN                
# participants affected / at risk     9/104 (8.65%)     4/107 (3.74%)     6/103 (5.83%)     10/103 (9.71%)     6/103 (5.83%)     1/16 (6.25%)     2/59 (3.39%)     2/36 (5.56%)  
# events     12     4     6     10     7     1     3     2  
ABDOMINAL PAIN UPPER                
# participants affected / at risk     5/104 (4.81%)     7/107 (6.54%)     5/103 (4.85%)     9/103 (8.74%)     12/103 (11.65%)     2/16 (12.50%)     5/59 (8.47%)     1/36 (2.78%)  
# events     5     8     7     9     15     2     6     1  
APHTHOUS STOMATITIS                
# participants affected / at risk     2/104 (1.92%)     2/107 (1.87%)     3/103 (2.91%)     4/103 (3.88%)     4/103 (3.88%)     2/16 (12.50%)     3/59 (5.08%)     0/36 (0.00%)  
# events     2     3     4     4     4     2     3     0  
CHEILITIS                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     1/103 (0.97%)     2/103 (1.94%)     2/103 (1.94%)     1/16 (6.25%)     0/59 (0.00%)     1/36 (2.78%)  
# events     1     0     1     4     2     2     0     1  
CONSTIPATION                
# participants affected / at risk     11/104 (10.58%)     5/107 (4.67%)     14/103 (13.59%)     9/103 (8.74%)     9/103 (8.74%)     1/16 (6.25%)     3/59 (5.08%)     2/36 (5.56%)  
# events     13     5     17     10     10     1     3     2  
DIARRHOEA                
# participants affected / at risk     23/104 (22.12%)     28/107 (26.17%)     27/103 (26.21%)     25/103 (24.27%)     29/103 (28.16%)     5/16 (31.25%)     14/59 (23.73%)     2/36 (5.56%)  
# events     31     40     29     30     36     5     18     2  
DRY MOUTH                
# participants affected / at risk     5/104 (4.81%)     14/107 (13.08%)     8/103 (7.77%)     12/103 (11.65%)     10/103 (9.71%)     2/16 (12.50%)     5/59 (8.47%)     2/36 (5.56%)  
# events     5     15     8     15     10     2     7     3  
DYSPEPSIA                
# participants affected / at risk     8/104 (7.69%)     6/107 (5.61%)     8/103 (7.77%)     9/103 (8.74%)     8/103 (7.77%)     1/16 (6.25%)     0/59 (0.00%)     1/36 (2.78%)  
# events     9     8     8     10     8     1     0     1  
GASTROOESOPHAGEAL REFLUX DISEASE                
# participants affected / at risk     5/104 (4.81%)     11/107 (10.28%)     3/103 (2.91%)     8/103 (7.77%)     10/103 (9.71%)     1/16 (6.25%)     2/59 (3.39%)     1/36 (2.78%)  
# events     5     12     4     9     11     2     2     1  
GINGIVAL PAIN                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     2/103 (1.94%)     0/103 (0.00%)     3/103 (2.91%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     2     0     4     1     0     0  
HAEMORRHOIDS                
# participants affected / at risk     7/104 (6.73%)     5/107 (4.67%)     2/103 (1.94%)     3/103 (2.91%)     1/103 (0.97%)     3/16 (18.75%)     0/59 (0.00%)     0/36 (0.00%)  
# events     7     6     2     3     1     3     0     0  
NAUSEA                
# participants affected / at risk     45/104 (43.27%)     41/107 (38.32%)     42/103 (40.78%)     55/103 (53.40%)     48/103 (46.60%)     10/16 (62.50%)     35/59 (59.32%)     4/36 (11.11%)  
# events     52     50     53     80     87     13     40     4  
ORAL PAIN                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     4/103 (3.88%)     1/16 (6.25%)     1/59 (1.69%)     1/36 (2.78%)  
# events     1     0     0     1     4     1     1     1  
PROCTALGIA                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     1/103 (0.97%)     1/103 (0.97%)     0/103 (0.00%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     0     1     1     1     0     1     1     0  
RECTAL HAEMORRHAGE                
# participants affected / at risk     3/104 (2.88%)     2/107 (1.87%)     2/103 (1.94%)     0/103 (0.00%)     2/103 (1.94%)     0/16 (0.00%)     0/59 (0.00%)     2/36 (5.56%)  
# events     3     2     2     0     2     0     0     2  
SALIVARY HYPERSECRETION                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     1/103 (0.97%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     1     0     0     1     0     0  
STOMACH DISCOMFORT                
# participants affected / at risk     3/104 (2.88%)     1/107 (0.93%)     0/103 (0.00%)     3/103 (2.91%)     0/103 (0.00%)     1/16 (6.25%)     3/59 (5.08%)     0/36 (0.00%)  
# events     4     1     0     3     0     1     3     0  
STOMATITIS                
# participants affected / at risk     2/104 (1.92%)     7/107 (6.54%)     5/103 (4.85%)     5/103 (4.85%)     4/103 (3.88%)     0/16 (0.00%)     0/59 (0.00%)     1/36 (2.78%)  
# events     2     8     5     7     5     0     0     1  
TOOTHACHE                
# participants affected / at risk     2/104 (1.92%)     3/107 (2.80%)     1/103 (0.97%)     0/103 (0.00%)     2/103 (1.94%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     2     3     1     0     2     1     0     0  
VOMITING                
# participants affected / at risk     5/104 (4.81%)     24/107 (22.43%)     15/103 (14.56%)     25/103 (24.27%)     17/103 (16.50%)     7/16 (43.75%)     11/59 (18.64%)     2/36 (5.56%)  
# events     7     27     21     28     23     8     14     2  
General disorders                  
ASTHENIA                
# participants affected / at risk     14/104 (13.46%)     9/107 (8.41%)     9/103 (8.74%)     20/103 (19.42%)     15/103 (14.56%)     1/16 (6.25%)     3/59 (5.08%)     3/36 (8.33%)  
# events     18     12     18     27     26     2     3     4  
CHEST DISCOMFORT                
# participants affected / at risk     3/104 (2.88%)     0/107 (0.00%)     1/103 (0.97%)     2/103 (1.94%)     0/103 (0.00%)     1/16 (6.25%)     2/59 (3.39%)     0/36 (0.00%)  
# events     3     0     1     2     0     1     3     0  
CHILLS                
# participants affected / at risk     35/104 (33.65%)     31/107 (28.97%)     31/103 (30.10%)     33/103 (32.04%)     35/103 (33.98%)     5/16 (31.25%)     26/59 (44.07%)     0/36 (0.00%)  
# events     38     39     34     37     39     6     29     0  
FATIGUE                
# participants affected / at risk     57/104 (54.81%)     65/107 (60.75%)     70/103 (67.96%)     51/103 (49.51%)     73/103 (70.87%)     11/16 (68.75%)     40/59 (67.80%)     5/36 (13.89%)  
# events     62     78     80     69     95     14     55     5  
IMPAIRED HEALING                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     0/103 (0.00%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     0     0     0     1     0     1     1     0  
INFLUENZA LIKE ILLNESS                
# participants affected / at risk     25/104 (24.04%)     24/107 (22.43%)     21/103 (20.39%)     19/103 (18.45%)     15/103 (14.56%)     6/16 (37.50%)     11/59 (18.64%)     0/36 (0.00%)  
# events     37     26     22     20     27     6     11     0  
INJECTION SITE ERYTHEMA                
# participants affected / at risk     13/104 (12.50%)     9/107 (8.41%)     14/103 (13.59%)     7/103 (6.80%)     13/103 (12.62%)     1/16 (6.25%)     4/59 (6.78%)     1/36 (2.78%)  
# events     13     9     14     7     13     1     4     1  
INJECTION SITE RASH                
# participants affected / at risk     6/104 (5.77%)     3/107 (2.80%)     0/103 (0.00%)     3/103 (2.91%)     6/103 (5.83%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     6     3     0     3     6     1     1     0  
INJECTION SITE REACTION                
# participants affected / at risk     10/104 (9.62%)     9/107 (8.41%)     5/103 (4.85%)     9/103 (8.74%)     11/103 (10.68%)     4/16 (25.00%)     21/59 (35.59%)     1/36 (2.78%)  
# events     12     9     5     9     11     4     21     1  
IRRITABILITY                
# participants affected / at risk     23/104 (22.12%)     25/107 (23.36%)     24/103 (23.30%)     15/103 (14.56%)     27/103 (26.21%)     3/16 (18.75%)     9/59 (15.25%)     0/36 (0.00%)  
# events     23     26     27     21     32     3     11     0  
NON-CARDIAC CHEST PAIN                
# participants affected / at risk     1/104 (0.96%)     2/107 (1.87%)     0/103 (0.00%)     2/103 (1.94%)     1/103 (0.97%)     2/16 (12.50%)     1/59 (1.69%)     0/36 (0.00%)  
# events     1     2     0     2     1     3     1     0  
PAIN                
# participants affected / at risk     8/104 (7.69%)     11/107 (10.28%)     9/103 (8.74%)     11/103 (10.68%)     5/103 (4.85%)     1/16 (6.25%)     11/59 (18.64%)     0/36 (0.00%)  
# events     8     11     10     12     5     1     12     0  
PYREXIA                
# participants affected / at risk     35/104 (33.65%)     27/107 (25.23%)     27/103 (26.21%)     40/103 (38.83%)     35/103 (33.98%)     7/16 (43.75%)     26/59 (44.07%)     0/36 (0.00%)  
# events     55     35     34     51     53     10     31     0  
TEMPERATURE INTOLERANCE                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     1     0     0     0     1     2     1     0  
Infections and infestations                  
BRONCHITIS                
# participants affected / at risk     3/104 (2.88%)     4/107 (3.74%)     1/103 (0.97%)     2/103 (1.94%)     1/103 (0.97%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     3     6     1     2     2     1     1     0  
EAR INFECTION                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     1/103 (0.97%)     1/103 (0.97%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     1     0     1     3     1     1     0     0  
EYE INFECTION                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     1/36 (2.78%)  
# events     2     0     0     0     0     1     0     1  
INFLUENZA                
# participants affected / at risk     1/104 (0.96%)     3/107 (2.80%)     0/103 (0.00%)     3/103 (2.91%)     3/103 (2.91%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     1     4     0     4     3     1     1     0  
LARYNGITIS                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     1     0     0     1     0     1     0     0  
ORAL CANDIDIASIS                
# participants affected / at risk     1/104 (0.96%)     1/107 (0.93%)     0/103 (0.00%)     2/103 (1.94%)     1/103 (0.97%)     1/16 (6.25%)     3/59 (5.08%)     0/36 (0.00%)  
# events     1     1     0     2     1     1     5     0  
PHARYNGITIS                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     2/103 (1.94%)     1/103 (0.97%)     1/103 (0.97%)     1/16 (6.25%)     1/59 (1.69%)     1/36 (2.78%)  
# events     1     0     2     1     3     1     1     1  
PHARYNGITIS STREPTOCOCCAL                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     1     0     0     0     2     0     0  
RECTAL ABSCESS                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     0     0     1     0     0  
SINUSITIS                
# participants affected / at risk     3/104 (2.88%)     3/107 (2.80%)     3/103 (2.91%)     5/103 (4.85%)     5/103 (4.85%)     2/16 (12.50%)     1/59 (1.69%)     2/36 (5.56%)  
# events     3     4     3     7     5     3     1     2  
TINEA VERSICOLOUR                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     0     0     1     0     0  
UPPER RESPIRATORY TRACT INFECTION                
# participants affected / at risk     3/104 (2.88%)     7/107 (6.54%)     1/103 (0.97%)     4/103 (3.88%)     7/103 (6.80%)     1/16 (6.25%)     6/59 (10.17%)     0/36 (0.00%)  
# events     3     7     1     4     8     1     7     0  
URINARY TRACT INFECTION                
# participants affected / at risk     3/104 (2.88%)     3/107 (2.80%)     3/103 (2.91%)     2/103 (1.94%)     1/103 (0.97%)     1/16 (6.25%)     2/59 (3.39%)     0/36 (0.00%)  
# events     4     3     3     2     2     1     2     0  
Investigations                  
BLOOD URIC ACID INCREASED                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     0/16 (0.00%)     3/59 (5.08%)     0/36 (0.00%)  
# events     0     1     0     0     0     0     5     0  
HEART RATE INCREASED                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     0/103 (0.00%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     1     0     0     1     0     1     1     0  
WEIGHT DECREASED                
# participants affected / at risk     9/104 (8.65%)     6/107 (5.61%)     8/103 (7.77%)     6/103 (5.83%)     9/103 (8.74%)     2/16 (12.50%)     8/59 (13.56%)     1/36 (2.78%)  
# events     9     6     8     8     10     2     8     1  
Metabolism and nutrition disorders                  
ANOREXIA                
# participants affected / at risk     10/104 (9.62%)     10/107 (9.35%)     8/103 (7.77%)     13/103 (12.62%)     11/103 (10.68%)     2/16 (12.50%)     4/59 (6.78%)     0/36 (0.00%)  
# events     11     10     8     18     15     2     5     0  
DECREASED APPETITE                
# participants affected / at risk     12/104 (11.54%)     7/107 (6.54%)     14/103 (13.59%)     16/103 (15.53%)     12/103 (11.65%)     6/16 (37.50%)     16/59 (27.12%)     1/36 (2.78%)  
# events     13     7     15     18     12     6     17     1  
HYPERAMYLASAEMIA                
# participants affected / at risk     1/104 (0.96%)     3/107 (2.80%)     1/103 (0.97%)     1/103 (0.97%)     1/103 (0.97%)     0/16 (0.00%)     3/59 (5.08%)     0/36 (0.00%)  
# events     2     4     1     1     2     0     3     0  
HYPERTRIGLYCERIDAEMIA                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     3/103 (2.91%)     1/103 (0.97%)     3/103 (2.91%)     0/16 (0.00%)     3/59 (5.08%)     0/36 (0.00%)  
# events     0     1     3     1     3     0     3     0  
HYPERURICAEMIA                
# participants affected / at risk     3/104 (2.88%)     1/107 (0.93%)     1/103 (0.97%)     0/103 (0.00%)     2/103 (1.94%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     3     1     1     0     3     1     1     0  
Musculoskeletal and connective tissue disorders                  
ARTHRALGIA                
# participants affected / at risk     21/104 (20.19%)     14/107 (13.08%)     22/103 (21.36%)     21/103 (20.39%)     19/103 (18.45%)     5/16 (31.25%)     11/59 (18.64%)     1/36 (2.78%)  
# events     24     20     26     25     21     7     13     1  
BACK PAIN                
# participants affected / at risk     5/104 (4.81%)     5/107 (4.67%)     7/103 (6.80%)     10/103 (9.71%)     9/103 (8.74%)     3/16 (18.75%)     5/59 (8.47%)     0/36 (0.00%)  
# events     5     5     7     13     11     3     5     0  
JOINT SWELLING                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     1/103 (0.97%)     1/103 (0.97%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     1     0     1     1     1     1     0     0  
MUSCLE SPASMS                
# participants affected / at risk     5/104 (4.81%)     4/107 (3.74%)     4/103 (3.88%)     6/103 (5.83%)     1/103 (0.97%)     0/16 (0.00%)     3/59 (5.08%)     2/36 (5.56%)  
# events     7     4     4     6     1     0     3     2  
MUSCLE TIGHTNESS                
# participants affected / at risk     1/104 (0.96%)     1/107 (0.93%)     0/103 (0.00%)     0/103 (0.00%)     2/103 (1.94%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     1     1     0     0     2     1     1     0  
MUSCULAR WEAKNESS                
# participants affected / at risk     4/104 (3.85%)     4/107 (3.74%)     0/103 (0.00%)     1/103 (0.97%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     4     5     0     1     1     2     0     0  
MUSCULOSKELETAL PAIN                
# participants affected / at risk     5/104 (4.81%)     4/107 (3.74%)     0/103 (0.00%)     1/103 (0.97%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     6     5     0     1     1     1     0     0  
MYALGIA                
# participants affected / at risk     17/104 (16.35%)     31/107 (28.97%)     20/103 (19.42%)     21/103 (20.39%)     27/103 (26.21%)     4/16 (25.00%)     12/59 (20.34%)     2/36 (5.56%)  
# events     17     34     20     30     33     5     15     2  
PAIN IN EXTREMITY                
# participants affected / at risk     4/104 (3.85%)     4/107 (3.74%)     0/103 (0.00%)     6/103 (5.83%)     4/103 (3.88%)     0/16 (0.00%)     2/59 (3.39%)     0/36 (0.00%)  
# events     5     4     0     7     5     0     2     0  
Nervous system disorders                  
AMNESIA                
# participants affected / at risk     1/104 (0.96%)     1/107 (0.93%)     2/103 (1.94%)     5/103 (4.85%)     1/103 (0.97%)     2/16 (12.50%)     1/59 (1.69%)     0/36 (0.00%)  
# events     1     1     3     6     1     2     1     0  
DISTURBANCE IN ATTENTION                
# participants affected / at risk     4/104 (3.85%)     7/107 (6.54%)     9/103 (8.74%)     7/103 (6.80%)     10/103 (9.71%)     0/16 (0.00%)     3/59 (5.08%)     0/36 (0.00%)  
# events     5     7     9     8     11     0     4     0  
DIZZINESS                
# participants affected / at risk     16/104 (15.38%)     19/107 (17.76%)     16/103 (15.53%)     21/103 (20.39%)     14/103 (13.59%)     7/16 (43.75%)     11/59 (18.64%)     2/36 (5.56%)  
# events     18     23     18     21     18     8     16     2  
DYSGEUSIA                
# participants affected / at risk     9/104 (8.65%)     23/107 (21.50%)     27/103 (26.21%)     33/103 (32.04%)     28/103 (27.18%)     7/16 (43.75%)     18/59 (30.51%)     7/36 (19.44%)  
# events     10     25     28     38     31     9     20     7  
HEADACHE                
# participants affected / at risk     45/104 (43.27%)     51/107 (47.66%)     41/103 (39.81%)     44/103 (42.72%)     54/103 (52.43%)     13/16 (81.25%)     29/59 (49.15%)     2/36 (5.56%)  
# events     60     66     46     52     67     13     35     2  
MEMORY IMPAIRMENT                
# participants affected / at risk     3/104 (2.88%)     2/107 (1.87%)     2/103 (1.94%)     3/103 (2.91%)     2/103 (1.94%)     1/16 (6.25%)     5/59 (8.47%)     1/36 (2.78%)  
# events     3     2     2     3     2     1     5     1  
MIGRAINE                
# participants affected / at risk     2/104 (1.92%)     1/107 (0.93%)     2/103 (1.94%)     5/103 (4.85%)     3/103 (2.91%)     4/16 (25.00%)     1/59 (1.69%)     1/36 (2.78%)  
# events     3     1     2     5     3     6     1     1  
PARAESTHESIA                
# participants affected / at risk     3/104 (2.88%)     5/107 (4.67%)     4/103 (3.88%)     6/103 (5.83%)     2/103 (1.94%)     1/16 (6.25%)     3/59 (5.08%)     0/36 (0.00%)  
# events     4     6     4     6     2     2     3     0  
SCIATICA                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     1     0     0     0     1     2     0     0  
SOMNOLENCE                
# participants affected / at risk     1/104 (0.96%)     0/107 (0.00%)     0/103 (0.00%)     2/103 (1.94%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     1     0     0     2     0     1     0     0  
TREMOR                
# participants affected / at risk     3/104 (2.88%)     3/107 (2.80%)     1/103 (0.97%)     3/103 (2.91%)     1/103 (0.97%)     2/16 (12.50%)     4/59 (6.78%)     0/36 (0.00%)  
# events     3     3     1     3     1     3     4     0  
TRIGEMINAL NEURALGIA                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     0     0     1     0     0  
Psychiatric disorders                  
ANXIETY                
# participants affected / at risk     18/104 (17.31%)     16/107 (14.95%)     9/103 (8.74%)     15/103 (14.56%)     17/103 (16.50%)     1/16 (6.25%)     8/59 (13.56%)     0/36 (0.00%)  
# events     21     19     10     17     20     1     11     0  
CONFUSIONAL STATE                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     2/103 (1.94%)     0/103 (0.00%)     3/103 (2.91%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     1     2     0     3     2     0     0  
DEPRESSION                
# participants affected / at risk     22/104 (21.15%)     22/107 (20.56%)     20/103 (19.42%)     29/103 (28.16%)     20/103 (19.42%)     1/16 (6.25%)     14/59 (23.73%)     4/36 (11.11%)  
# events     25     29     23     34     26     1     17     5  
INSOMNIA                
# participants affected / at risk     40/104 (38.46%)     36/107 (33.64%)     29/103 (28.16%)     40/103 (38.83%)     41/103 (39.81%)     7/16 (43.75%)     23/59 (38.98%)     7/36 (19.44%)  
# events     50     40     37     46     48     7     27     7  
MOOD SWINGS                
# participants affected / at risk     2/104 (1.92%)     1/107 (0.93%)     1/103 (0.97%)     3/103 (2.91%)     1/103 (0.97%)     1/16 (6.25%)     2/59 (3.39%)     0/36 (0.00%)  
# events     3     1     1     4     1     1     2     0  
Renal and urinary disorders                  
CHROMATURIA                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     1     0     1     0     0  
HAEMATURIA                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     1/103 (0.97%)     1/103 (0.97%)     1/103 (0.97%)     1/16 (6.25%)     1/59 (1.69%)     1/36 (2.78%)  
# events     0     0     1     1     1     1     1     1  
NOCTURIA                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     2/103 (1.94%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     2     0     1     0     0  
POLLAKIURIA                
# participants affected / at risk     1/104 (0.96%)     4/107 (3.74%)     6/103 (5.83%)     3/103 (2.91%)     6/103 (5.83%)     2/16 (12.50%)     5/59 (8.47%)     0/36 (0.00%)  
# events     1     4     6     3     6     2     5     0  
URETHRAL OBSTRUCTION                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     0     0     1     0     0  
URINARY RETENTION                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     0     0     0     1     0     0  
Reproductive system and breast disorders                  
ERECTILE DYSFUNCTION                
# participants affected / at risk     2/104 (1.92%)     2/107 (1.87%)     0/103 (0.00%)     0/103 (0.00%)     2/103 (1.94%)     1/16 (6.25%)     5/59 (8.47%)     0/36 (0.00%)  
# events     2     2     0     0     2     1     5     0  
VULVOVAGINAL PRURITUS                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     1     0     0     0     1     0     0  
Respiratory, thoracic and mediastinal disorders                  
COUGH                
# participants affected / at risk     20/104 (19.23%)     18/107 (16.82%)     22/103 (21.36%)     17/103 (16.50%)     19/103 (18.45%)     2/16 (12.50%)     8/59 (13.56%)     2/36 (5.56%)  
# events     26     27     25     21     25     2     9     2  
DYSPNOEA                
# participants affected / at risk     15/104 (14.42%)     18/107 (16.82%)     12/103 (11.65%)     16/103 (15.53%)     20/103 (19.42%)     4/16 (25.00%)     10/59 (16.95%)     2/36 (5.56%)  
# events     20     23     12     21     25     4     14     2  
DYSPNOEA EXERTIONAL                
# participants affected / at risk     6/104 (5.77%)     6/107 (5.61%)     2/103 (1.94%)     5/103 (4.85%)     11/103 (10.68%)     1/16 (6.25%)     4/59 (6.78%)     0/36 (0.00%)  
# events     6     6     2     6     14     1     4     0  
EPISTAXIS                
# participants affected / at risk     3/104 (2.88%)     3/107 (2.80%)     2/103 (1.94%)     6/103 (5.83%)     3/103 (2.91%)     0/16 (0.00%)     2/59 (3.39%)     0/36 (0.00%)  
# events     3     4     2     7     3     0     2     0  
INCREASED UPPER AIRWAY SECRETION                
# participants affected / at risk     0/104 (0.00%)     0/107 (0.00%)     3/103 (2.91%)     2/103 (1.94%)     2/103 (1.94%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     0     3     2     2     1     0     0  
OROPHARYNGEAL PAIN                
# participants affected / at risk     3/104 (2.88%)     2/107 (1.87%)     11/103 (10.68%)     9/103 (8.74%)     5/103 (4.85%)     2/16 (12.50%)     2/59 (3.39%)     1/36 (2.78%)  
# events     3     2     12     10     5     2     2     1  
PARANASAL SINUS HYPERSECRETION                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     0/103 (0.00%)     1/103 (0.97%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     1     0     1     1     1     0     0  
POSTNASAL DRIP                
# participants affected / at risk     1/104 (0.96%)     2/107 (1.87%)     0/103 (0.00%)     0/103 (0.00%)     0/103 (0.00%)     1/16 (6.25%)     1/59 (1.69%)     0/36 (0.00%)  
# events     1     2     0     0     0     1     1     0  
PRODUCTIVE COUGH                
# participants affected / at risk     5/104 (4.81%)     2/107 (1.87%)     0/103 (0.00%)     2/103 (1.94%)     4/103 (3.88%)     0/16 (0.00%)     3/59 (5.08%)     0/36 (0.00%)  
# events     5     2     0     2     5     0     5     0  
SINUS CONGESTION                
# participants affected / at risk     2/104 (1.92%)     1/107 (0.93%)     3/103 (2.91%)     3/103 (2.91%)     4/103 (3.88%)     1/16 (6.25%)     2/59 (3.39%)     0/36 (0.00%)  
# events     3     1     3     3     4     1     2     0  
Skin and subcutaneous tissue disorders                  
ALOPECIA                
# participants affected / at risk     27/104 (25.96%)     36/107 (33.64%)     30/103 (29.13%)     30/103 (29.13%)     35/103 (33.98%)     5/16 (31.25%)     19/59 (32.20%)     2/36 (5.56%)  
# events     28     41     34     31     38     5     19     2  
DERMATITIS                
# participants affected / at risk     4/104 (3.85%)     1/107 (0.93%)     1/103 (0.97%)     4/103 (3.88%)     1/103 (0.97%)     2/16 (12.50%)     2/59 (3.39%)     0/36 (0.00%)  
# events     5     1     1     5     1     4     2     0  
DRY SKIN                
# participants affected / at risk     17/104 (16.35%)     12/107 (11.21%)     9/103 (8.74%)     22/103 (21.36%)     17/103 (16.50%)     3/16 (18.75%)     9/59 (15.25%)     4/36 (11.11%)  
# events     17     14     10     24     18     3     13     4  
ECZEMA                
# participants affected / at risk     4/104 (3.85%)     2/107 (1.87%)     7/103 (6.80%)     3/103 (2.91%)     4/103 (3.88%)     2/16 (12.50%)     2/59 (3.39%)     0/36 (0.00%)  
# events     7     2     8     4     4     2     2     0  
ERYTHEMA                
# participants affected / at risk     3/104 (2.88%)     4/107 (3.74%)     6/103 (5.83%)     3/103 (2.91%)     2/103 (1.94%)     0/16 (0.00%)     0/59 (0.00%)     0/36 (0.00%)  
# events     3     4     6     3     2     0     0     0  
INCREASED TENDENCY TO BRUISE                
# participants affected / at risk     0/104 (0.00%)     1/107 (0.93%)     1/103 (0.97%)     0/103 (0.00%)     1/103 (0.97%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     1     1     0     1     1     0     0  
PRURITUS                
# participants affected / at risk     16/104 (15.38%)     19/107 (17.76%)     19/103 (18.45%)     23/103 (22.33%)     19/103 (18.45%)     1/16 (6.25%)     11/59 (18.64%)     3/36 (8.33%)  
# events     20     23     28     35     24     1     17     3  
RASH                
# participants affected / at risk     6/104 (5.77%)     3/107 (2.80%)     6/103 (5.83%)     9/103 (8.74%)     9/103 (8.74%)     1/16 (6.25%)     1/59 (1.69%)     2/36 (5.56%)  
# events     7     5     6     12     9     1     1     2  
RASH ERYTHEMATOUS                
# participants affected / at risk     2/104 (1.92%)     7/107 (6.54%)     5/103 (4.85%)     4/103 (3.88%)     3/103 (2.91%)     0/16 (0.00%)     2/59 (3.39%)     0/36 (0.00%)  
# events     3     9     6     9     3     0     3     0  
RASH MACULAR                
# participants affected / at risk     0/104 (0.00%)     2/107 (1.87%)     3/103 (2.91%)     6/103 (5.83%)     6/103 (5.83%)     0/16 (0.00%)     2/59 (3.39%)     0/36 (0.00%)  
# events     0     2     3     9     7     0     3     0  
RASH MACULO-PAPULAR                
# participants affected / at risk     5/104 (4.81%)     6/107 (5.61%)     1/103 (0.97%)     5/103 (4.85%)     4/103 (3.88%)     1/16 (6.25%)     8/59 (13.56%)     0/36 (0.00%)  
# events     7     7     1     5     5     1     9     0  
RASH PAPULAR                
# participants affected / at risk     8/104 (7.69%)     9/107 (8.41%)     8/103 (7.77%)     17/103 (16.50%)     14/103 (13.59%)     1/16 (6.25%)     4/59 (6.78%)     0/36 (0.00%)  
# events     10     9     9     23     17     1     6     0  
RASH PRURITIC                
# participants affected / at risk     4/104 (3.85%)     1/107 (0.93%)     4/103 (3.88%)     1/103 (0.97%)     5/103 (4.85%)     1/16 (6.25%)     5/59 (8.47%)     1/36 (2.78%)  
# events     5     1     4     1     6     1     7     1  
SKIN LESION                
# participants affected / at risk     4/104 (3.85%)     4/107 (3.74%)     1/103 (0.97%)     1/103 (0.97%)     2/103 (1.94%)     0/16 (0.00%)     1/59 (1.69%)     2/36 (5.56%)  
# events     4     4     1     1     4     0     1     2  
URTICARIA                
# participants affected / at risk     2/104 (1.92%)     3/107 (2.80%)     0/103 (0.00%)     0/103 (0.00%)     1/103 (0.97%)     2/16 (12.50%)     0/59 (0.00%)     0/36 (0.00%)  
# events     2     3     0     0     1     2     0     0  
Vascular disorders                  
HYPERTENSION                
# participants affected / at risk     6/104 (5.77%)     2/107 (1.87%)     4/103 (3.88%)     1/103 (0.97%)     5/103 (4.85%)     0/16 (0.00%)     3/59 (5.08%)     0/36 (0.00%)  
# events     6     2     4     1     5     0     4     0  
HYPOTENSION                
# participants affected / at risk     0/104 (0.00%)     3/107 (2.80%)     1/103 (0.97%)     1/103 (0.97%)     3/103 (2.91%)     1/16 (6.25%)     0/59 (0.00%)     0/36 (0.00%)  
# events     0     4     1     1     3     1     0     0  
Events were collected by systematic assessment



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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.


Limitations and Caveats
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
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Results Point of Contact:  
Name/Title: Vice President, Late Stage Development Group Leader
Organization: Merck, Sharp and Dohme
e-mail: ClinicalTrialsDisclosure@merck.com


No publications provided by Merck Sharp & Dohme Corp.

Publications automatically indexed to this study:

Responsible Party: Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier: NCT00423670     History of Changes
Other Study ID Numbers: P03523, EudraCT No. 2006-002543-92
Study First Received: January 17, 2007
Results First Received: May 13, 2011
Last Updated: March 17, 2014
Health Authority: United States: Food and Drug Administration