A Randomized, Clinical Trial of Vitamin E and Memantine in Alzheimer's Disease (TEAM-AD)

This study has been completed.
Sponsor:
Collaborators:
Forest Laboratories
DSM Nutritional Products, Inc.
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00235716
First received: October 6, 2005
Last updated: July 14, 2014
Last verified: July 2014
Results First Received: December 6, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Factorial Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Alzheimer's Disease
Interventions: Drug: dl-alpha-tocopherol
Drug: Memantine
Drug: 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
Recruitment initiated in August, 2007 and concluded in March, 2012. Enrollment took place at 14 VA medical centers.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Vitamin E Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine (Namenda) Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
Vitamin E + Memantine 2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Placebo Matching placebo pills for vitamin E and memantine

Participant Flow:   Overall Study
    Vitamin E     Memantine (Namenda)     Vitamin E + Memantine     Placebo  
STARTED     152     155     154     152  
COMPLETED     90     88     89     90  
NOT COMPLETED     62     67     65     62  
Death                 26                 39                 32                 31  
Withdrawal by Subject                 23                 19                 17                 18  
Lost to Follow-up                 12                 7                 14                 10  
Adverse Event                 1                 1                 1                 0  
Physician Decision                 0                 1                 1                 3  



  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
Vitamin E Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine (Namenda) Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
Vitamin E + Memantine 2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Placebo Matching placebo pills for vitamin E and memantine
Total Total of all reporting groups

Baseline Measures
    Vitamin E     Memantine (Namenda)     Vitamin E + Memantine     Placebo     Total  
Number of Participants  
[units: participants]
  152     155     154     152     613  
Age  
[units: years]
Mean ± Standard Deviation
  78.6  ± 7.2     78.8  ± 7.2     78.3  ± 7.0     79.4  ± 7.0     78.8  ± 7.1  
Gender  
[units: participants]
         
Female     6     6     4     3     19  
Male     146     149     150     149     594  
Ethnicity (NIH/OMB)  
[units: participants]
         
Hispanic or Latino     17     15     15     19     66  
Not Hispanic or Latino     135     140     139     133     547  
Unknown or Not Reported     0     0     0     0     0  
Race (NIH/OMB)  
[units: participants]
         
American Indian or Alaska Native     0     0     0     1     1  
Asian     0     1     0     0     1  
Native Hawaiian or Other Pacific Islander     0     1     0     0     1  
Black or African American     21     21     18     20     80  
White     130     132     136     131     529  
More than one race     1     0     0     0     1  
Unknown or Not Reported     0     0     0     0     0  
Region of Enrollment  
[units: participants]
         
United States     152     155     154     152     613  
Education  
[units: participants]
         
<High School Graduation     41     41     26     29     137  
High School Graduation     46     48     57     56     207  
Some College     27     38     37     33     135  
College Graduation or Advanced Degree     38     28     34     34     134  
Apolipoprotein E ε4 status [1]
[units: participants]
         
Non-carriers     47     48     59     55     209  
One ε4 allele     39     44     44     38     165  
Two ε4 alleles     10     13     8     10     41  
Not Tested     56     50     43     49     198  
Concomitant Medications Acetylcholinesterase Inhibitors (AChEI)  
[units: participants]
         
Donepezil     104     100     100     96     400  
Galantamine     43     47     49     55     194  
Rivastigmine     5     8     4     1     18  
None     0     0     1     0     1  
Weeks from AChEI Initiation to Randomization  
[units: participants]
         
≤ 12 weeks     46     36     49     37     168  
> 12 weeks     105     119     104     115     443  
Missing     1     0     1     0     2  
Alzheimer's Disease Cooperative Study/Activities of Daily Living Inventory  
[units: units on a scale]
Mean ± Standard Deviation
  56.6  ± 14.9     57.3  ± 14.2     56.4  ± 14.0     56.8  ± 13.7     56.8  ± 14.2  
Mini-Mental State Examination  
[units: units on a scale]
Mean ± Standard Deviation
  21.3  ± 3.3     20.8  ± 3.8     21.3  ± 3.4     20.8  ± 3.8     21.0  ± 3.6  
Alzheimer's Disease Assessment Scale - Cognitive portion  
[units: units on a scale]
Mean ± Standard Deviation
  18.5  ± 8.8     19.5  ± 7.9     18.0  ± 8.4     19.1  ± 8.4     18.8  ± 8.4  
Neuropsychiatric Inventory  
[units: units on a scale]
Mean ± Standard Deviation
  12.2  ± 13.3     12.1  ± 13.1     12.3  ± 13.3     13.5  ± 14.2     12.5  ± 13.4  
Caregiver Activity Survey  
[units: hours per day]
Mean ± Standard Deviation
  7.3  ± 14.3     6.7  ± 9.0     6.6  ± 10.5     6.5  ± 9.2     6.8  ± 10.9  
Dependence Scale [2]
[units: participants]
         
Level 0     5     6     8     3     22  
Level 1     8     6     8     5     27  
Level 2     85     91     80     79     335  
Level 3     31     35     31     37     134  
Level 4     4     7     10     8     29  
Level 5     19     10     17     20     66  
[1] Data collected through genetic sub-study with separate informed consent.
[2] Higher the level the more dependence / less independence.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Alzheimer's Disease Cooperative Study/Activities of Daily Living (ADCS/ADL) Inventory Change From Baseline   [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]

2.  Primary:   Mini-Mental State Examination Change From Baseline   [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]

3.  Primary:   Alzheimer's Disease Assessment Scale - Cognitive (ADAS-cog) Change From Baseline   [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]

4.  Primary:   Neuropsychiatric Inventory Change From Baseline   [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]

5.  Primary:   Caregiver Activity Survey Change From Baseline   [ Time Frame: 6, 12, 18, 24, 30, 36, 42 and 48 months minus baseline ]

6.  Secondary:   Dependence Scale: Time to Event Analysis (Increase of of One Dependence Level)   [ Time Frame: Every 6 months to a maximum of 4 years ]

7.  Other Pre-specified:   All-cause Mortality   [ Time Frame: up to 4 years ]


  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   0%  

Reporting Groups
  Description
Vitamin E Alpha-tocopherol (vitamin E in the form of dl-alpha-tocopheryl acetate), 2000 international units (IU) per day, taken as one 1000 IU hard-gelatin, liquid-filled capsules twice a day plus matching memantine placebos.
Memantine Memantine 20 mg per day, titrated over four weeks to a maintenance dosage of 10 mg pills taken twice a day plus matching vitamin E placebo.
Vitamin E + Memantine 2000 IU of Alpha-tocopherol (vitamin E) per day plus 20 mg memantine per day.
Placebo Matching placebo pills for vitamin E and memantine

Other Adverse Events
    Vitamin E     Memantine     Vitamin E + Memantine     Placebo  
Total, other (not including serious) adverse events          
# participants affected / at risk     91/152     97/155     90/154     89/152  
Blood and lymphatic system disorders          
Anaemia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Anaemia macrocytic † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Haemorrhagic disorder † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Pancytopenia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Thrombocytopenia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Cardiac disorders          
Angina pectoris † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Arrhythmia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Atrial fibrillation † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Bradycardia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Cardiac failure † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Cardiac failure congestive † 1        
# participants affected / at risk     2/152 (1.32%)     3/155 (1.94%)     2/154 (1.30%)     2/152 (1.32%)  
# events     2     3     2     2  
Cardiomyopathy † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Coronary artery insufficiency † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Coronary artery occlusion † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Sick sinus syndrome † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     2/152 (1.32%)  
# events     0     0     0     2  
Congenital, familial and genetic disorders          
Arteriovenous malformation † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Dermoid cyst † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Ear and labyrinth disorders          
Hearing impaired † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Hypoacusis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Vertigo † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     1     0     1  
Vestibular disorder † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Eye disorders          
Age-related macular degeneration † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Blindness † 1        
# participants affected / at risk     0/152 (0.00%)     2/155 (1.29%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     3     0     0  
Cataract † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     1/154 (0.65%)     0/152 (0.00%)  
# events     1     1     1     0  
Dry eye † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Entropion † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     2     0  
Macular degeneration † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Refraction disorder † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     1     0     1  
Retinal haemorrhage † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     2     0  
Vision blurred † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Gastrointestinal disorders          
Abdominal pain † 1        
# participants affected / at risk     1/152 (0.66%)     2/155 (1.29%)     0/154 (0.00%)     2/152 (1.32%)  
# events     1     2     0     2  
Abdominal pain upper † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     1     0     1     1  
Constipation † 1        
# participants affected / at risk     2/152 (1.32%)     1/155 (0.65%)     1/154 (0.65%)     2/152 (1.32%)  
# events     2     1     1     2  
Diarrhoea † 1        
# participants affected / at risk     7/152 (4.61%)     4/155 (2.58%)     8/154 (5.19%)     5/152 (3.29%)  
# events     8     8     8     5  
Dyspepsia † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Eructation † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     0     0     1     1  
Faecaloma † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Flatulence † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Gastric ulcer † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Gastritis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     2/152 (1.32%)  
# events     0     0     0     2  
Gastrointestinal haemorrhage † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Gastrooesophageal reflux disease † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     1     0     1     0  
Haematochezia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Haemorrhoids † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     1     0     1     0  
Hiatus hernia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Hypoaesthesia oral † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Nausea † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     3/152 (1.97%)  
# events     0     1     0     3  
Oesophageal disorder † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Oral mucosal erythema † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Rectal haemorrhage † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     2/154 (1.30%)     0/152 (0.00%)  
# events     1     1     2     0  
Retching † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Small intestinal haemorrhage † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     2     0     0  
Toothache † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Vomiting † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     1     0     0     1  
General disorders          
Asthenia † 1        
# participants affected / at risk     2/152 (1.32%)     0/155 (0.00%)     2/154 (1.30%)     1/152 (0.66%)  
# events     2     0     2     1  
Chest discomfort † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Chest pain † 1        
# participants affected / at risk     1/152 (0.66%)     2/155 (1.29%)     3/154 (1.95%)     1/152 (0.66%)  
# events     2     2     3     1  
Cyst † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Device occlusion † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Fatigue † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Hernia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Influenza like illness † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Irritability † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Malaise † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     0     0     1     1  
Non-cardiac chest pain † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     0     0     1     1  
Oedema peripheral † 1        
# participants affected / at risk     2/152 (1.32%)     1/155 (0.65%)     0/154 (0.00%)     2/152 (1.32%)  
# events     2     1     0     2  
Pain † 1        
# participants affected / at risk     0/152 (0.00%)     2/155 (1.29%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     2     0     1  
Pyrexia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Xerosis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Hepatobiliary disorders          
Gallbladder pain † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Infections and infestations          
Abdominal abscess † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Abscess oral † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Breast cellulitis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Bronchitis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     3/152 (1.97%)  
# events     1     0     0     3  
Cellulitis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     1     0     1     0  
Cellulitis staphylococcal † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Fungal skin infection † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Furuncle † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Gastric infection † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Gastroenteritis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Herpes zoster † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Hordeolum † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Influenza † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     0     0     1     1  
Labyrinthitis † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Lung infection † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Lymph gland infection † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Nasopharyngitis † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Onychomycosis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     1     0     0     1  
Orchitis † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Otitis externa † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Paronychia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Pneumonia † 1        
# participants affected / at risk     1/152 (0.66%)     2/155 (1.29%)     3/154 (1.95%)     0/152 (0.00%)  
# events     1     2     3     0  
Respiratory tract infection fungal † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Sepsis † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Tinea cruris † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Tooth abscess † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Tracheobronchitis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Upper respiratory tract infection † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     2/152 (1.32%)  
# events     1     0     0     2  
Urinary tract infection † 1        
# participants affected / at risk     2/152 (1.32%)     5/155 (3.23%)     6/154 (3.90%)     2/152 (1.32%)  
# events     2     6     7     3  
Viral infection † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Injury, poisoning and procedural complications          
Accident at home † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     1/154 (0.65%)     0/152 (0.00%)  
# events     1     1     1     0  
Arthropod bite † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Contusion † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     1/154 (0.65%)     1/152 (0.66%)  
# events     0     1     1     1  
Drug dose omission † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     1     0     1     1  
Drug prescribing error † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Exposure to chemical pollution † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Face injury † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Fall † 1        
# participants affected / at risk     31/152 (20.39%)     28/155 (18.06%)     37/154 (24.03%)     31/152 (20.39%)  
# events     58     39     65     48  
Foot fracture † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Hand fracture † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Humerus fracture † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
In-stent coronary artery restenosis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Incorrect dose administered † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Injury † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     5/154 (3.25%)     2/152 (1.32%)  
# events     1     1     5     2  
Joint injury † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Laceration † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     1     0     1  
Ligament sprain † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Post procedural complication † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Road traffic accident † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     1     0     1     1  
Thermal burn † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Upper limb fracture † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Investigations          
Alanine aminotransferase increased † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Aspartate aminotransferase increased † 1        
# participants affected / at risk     2/152 (1.32%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     2     0     0     0  
Blood albumin abnormal † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Blood bicarbonate increased † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Blood cholesterol increased † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Blood creatinine increased † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Blood glucose increased † 1        
# participants affected / at risk     0/152 (0.00%)     2/155 (1.29%)     3/154 (1.95%)     1/152 (0.66%)  
# events     0     2     3     1  
Blood homocysteine increased † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Blood potassium increased † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     1     0     1     1  
Blood pressure increased † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Blood triglycerides increased † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Blood urea increased † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     1     0     0     1  
Culture negative † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Full blood count increased † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Glycosylated haemoglobin increased † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Heart rate decreased † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Hepatic enzyme increased † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
High density lipoprotein increased † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
International normalised ratio increased † 1        
# participants affected / at risk     2/152 (1.32%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     2     0     0     0  
Laboratory test abnormal † 1        
# participants affected / at risk     4/152 (2.63%)     5/155 (3.23%)     3/154 (1.95%)     3/152 (1.97%)  
# events     4     5     4     3  
Prostatic specific antigen increased † 1        
# participants affected / at risk     0/152 (0.00%)     2/155 (1.29%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     2     1     0  
Weight decreased † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Metabolism and nutrition disorders          
Decreased appetite † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Dehydration † 1        
# participants affected / at risk     1/152 (0.66%)     3/155 (1.94%)     1/154 (0.65%)     0/152 (0.00%)  
# events     1     4     1     0  
Diabetes mellitus inadequate control † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Failure to thrive † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     2/152 (1.32%)  
# events     0     0     0     2  
Gout † 1        
# participants affected / at risk     2/152 (1.32%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     2     0     0     0  
Hyperglycaemia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Hypoglycaemia † 1        
# participants affected / at risk     2/152 (1.32%)     1/155 (0.65%)     1/154 (0.65%)     0/152 (0.00%)  
# events     2     1     1     0  
Musculoskeletal and connective tissue disorders          
Arthralgia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     2/152 (1.32%)  
# events     0     0     1     2  
Arthritis † 1        
# participants affected / at risk     0/152 (0.00%)     2/155 (1.29%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     2     1     0  
Back pain † 1        
# participants affected / at risk     2/152 (1.32%)     3/155 (1.94%)     0/154 (0.00%)     3/152 (1.97%)  
# events     4     3     0     3  
Bursitis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     0     0     1     1  
Chondrocalcinosis pyrophosphate † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Exostosis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Flank pain † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Groin pain † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Joint swelling † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Muscle spasms † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     1/154 (0.65%)     2/152 (1.32%)  
# events     1     1     1     3  
Musculoskeletal chest pain † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     2     0     0     2  
Musculoskeletal pain † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Neck pain † 1        
# participants affected / at risk     2/152 (1.32%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     2     0     0     0  
Osteoarthritis † 1        
# participants affected / at risk     2/152 (1.32%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     2     0     0     1  
Osteoporosis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Pain in extremity † 1        
# participants affected / at risk     0/152 (0.00%)     2/155 (1.29%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     3     0     1  
Rotator cuff syndrome † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Spinal column stenosis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Synovial cyst † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)          
Acute myeloid leukaemia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Basal cell carcinoma † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     2/154 (1.30%)     1/152 (0.66%)  
# events     0     1     3     1  
Bladder neoplasm † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Bone neoplasm malignant † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Gastric cancer † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Lip and/or oral cavity cancer † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Lung neoplasm † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Neoplasm skin † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Neuroendocrine carcinoma of the skin † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Non-small cell lung cancer † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Prostate cancer † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     2/152 (1.32%)  
# events     0     0     0     2  
Skin cancer † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Squamous cell carcinoma † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     2     0  
Squamous cell carcinoma of skin † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Nervous system disorders          
Altered state of consciousness † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Aphasia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Cerebrovascular accident † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Dementia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Dizziness † 1        
# participants affected / at risk     6/152 (3.95%)     7/155 (4.52%)     5/154 (3.25%)     3/152 (1.97%)  
# events     6     8     5     3  
Dizziness postural † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Dyskinesia † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Headache † 1        
# participants affected / at risk     1/152 (0.66%)     4/155 (2.58%)     1/154 (0.65%)     0/152 (0.00%)  
# events     1     5     1     0  
Hemiparesis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Hypersomnia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Hypoaesthesia † 1        
# participants affected / at risk     0/152 (0.00%)     2/155 (1.29%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     2     0     1  
Lethargy † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     1     0     0     1  
Loss of consciousness † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Mental impairment † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Radial nerve palsy † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Somnolence † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     1     0     1     1  
Syncope † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     3/154 (1.95%)     3/152 (1.97%)  
# events     0     1     3     4  
Tremor † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Trigeminal neuralgia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Unresponsive to stimuli † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Visual field defect † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Psychiatric disorders          
Abnormal behaviour † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     2/154 (1.30%)     2/152 (1.32%)  
# events     1     0     2     2  
Abnormal sleep-related event † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Aggression † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Agitation † 1        
# participants affected / at risk     2/152 (1.32%)     0/155 (0.00%)     1/154 (0.65%)     2/152 (1.32%)  
# events     2     0     1     2  
Alcohol abuse † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Anxiety † 1        
# participants affected / at risk     1/152 (0.66%)     2/155 (1.29%)     1/154 (0.65%)     0/152 (0.00%)  
# events     1     2     1     0  
Apathy † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Confusional state † 1        
# participants affected / at risk     2/152 (1.32%)     1/155 (0.65%)     2/154 (1.30%)     0/152 (0.00%)  
# events     2     1     2     0  
Delusion † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Depressed mood † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     1     0     1  
Depression † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     1     0     1  
Disorientation † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Hallucination † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     2/154 (1.30%)     1/152 (0.66%)  
# events     1     1     2     1  
Insomnia † 1        
# participants affected / at risk     1/152 (0.66%)     2/155 (1.29%)     0/154 (0.00%)     1/152 (0.66%)  
# events     1     2     0     1  
Mental status changes † 1        
# participants affected / at risk     2/152 (1.32%)     1/155 (0.65%)     3/154 (1.95%)     1/152 (0.66%)  
# events     2     1     3     2  
Nightmare † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Paranoia † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Self injurious behaviour † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Social avoidant behaviour † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Renal and urinary disorders          
Dysuria † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     2/154 (1.30%)     0/152 (0.00%)  
# events     0     0     2     0  
Haematuria † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Incontinence † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Nephrolithiasis † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     1     0     1     1  
Renal artery stenosis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Renal cyst † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Renal failure † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Renal failure chronic † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Renal impairment † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Reproductive system and breast disorders          
Benign prostatic hyperplasia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Breast discharge † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Prostatomegaly † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Spermatocele † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Respiratory, thoracic and mediastinal disorders          
Chronic obstructive pulmonary disease † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     2/152 (1.32%)  
# events     1     0     0     4  
Cough † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Dyspnoea † 1        
# participants affected / at risk     3/152 (1.97%)     1/155 (0.65%)     0/154 (0.00%)     1/152 (0.66%)  
# events     3     1     0     1  
Epistaxis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     2/152 (1.32%)  
# events     0     0     2     2  
Haemoptysis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Oropharyngeal pain † 1        
# participants affected / at risk     0/152 (0.00%)     2/155 (1.29%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     2     0     0  
Paranasal sinus hypersecretion † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Respiratory distress † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Rhinitis seasonal † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Sneezing † 1        
# participants affected / at risk     0/152 (0.00%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     0     1     0     0  
Tracheomalacia † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Wheezing † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     2/152 (1.32%)  
# events     1     0     0     2  
Skin and subcutaneous tissue disorders          
Decubitus ulcer † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Dermatitis † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     2/152 (1.32%)  
# events     0     0     0     2  
Dermatitis allergic † 1        
# participants affected / at risk     1/152 (0.66%)     1/155 (0.65%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     1     0     0  
Dermatitis contact † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     0/154 (0.00%)     1/152 (0.66%)  
# events     0     0     0     1  
Dermatitis diaper † 1        
# participants affected / at risk     1/152 (0.66%)     0/155 (0.00%)     0/154 (0.00%)     0/152 (0.00%)  
# events     1     0     0     0  
Eczema † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     0/152 (0.00%)  
# events     0     0     1     0  
Pruritus † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)     1/152 (0.66%)  
# events     0     0     1     1  
Purpura senile † 1        
# participants affected / at risk     0/152 (0.00%)     0/155 (0.00%)     1/154 (0.65%)   &nb