The Efficacy and Safety of Sildenafil Citrate Used in Combination With Intravenous Epoprostenol in PAH

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00159861
First received: September 8, 2005
Last updated: December 20, 2013
Last verified: December 2013
Results First Received: April 2, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver);   Primary Purpose: Treatment
Condition: Pulmonary Hypertension
Intervention: Drug: Sildenafil citrate

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Subjects were entered into the open-label extension study portion upon completion of the preceding 16-week, placebo controlled core study portion or, for subjects who required a change in epoprostenol dose due to clinical deterioration, after at least 4 weeks in the core study portion.

Reporting Groups
  Description
Placebo: Core Study / Sildenafil: Extension Study Core Study: Placebo (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration); Extension Study: Sildenafil (until last enrolled subject completed 3 years of treatment) - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sildenafil: Core Study / Sildenafil: Extension Study Core Study (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration): Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study (until last enrolled subject completed 3 years of treatment): Sildenafil - initial dose 20 mg TID, may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator

Participant Flow for 2 periods

Period 1:   Core Study - 16 Weeks
    Placebo: Core Study / Sildenafil: Extension Study     Sildenafil: Core Study / Sildenafil: Extension Study  
STARTED     133     134  
Treated     131     134  
COMPLETED     108 [1]   122 [2]
NOT COMPLETED     25     12  
Death                 3                 0  
Adverse Event                 12                 6  
Lack of Efficacy                 2                 3  
Reason Unspecified                 5                 3  
Subject Defaulted                 1                 0  
Randomized but not Treated                 2                 0  
[1] Entered A1481153: 115; Did not enter A1481153: 16
[2] Entered A1481153: 127; Did not enter A1481153: 7

Period 2:   Extension Study - up to 3 Years
    Placebo: Core Study / Sildenafil: Extension Study     Sildenafil: Core Study / Sildenafil: Extension Study  
STARTED     115 [1]   127 [1]
Treated     115     127  
COMPLETED     53     56  
NOT COMPLETED     62     71  
Death                 24                 28  
Adverse Event                 14                 14  
Lack of Efficacy                 5                 1  
Reason Unspecified                 12                 19  
Withdrawal by Subject                 7                 9  
[1] Subjects may have entered extension study after 4 weeks in core study (prior to completion).



  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
Placebo/Sildenafil Core Study: Placebo; Extension Study: Sildenafil - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sildenafil/Sildenafil Study A1481141: Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study A1481153: Sildenafil - initial dose 20 mg TID, may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Total Total of all reporting groups

Baseline Measures
    Placebo/Sildenafil     Sildenafil/Sildenafil     Total  
Number of Participants  
[units: participants]
  131     134     265  
Age, Customized  
[units: participants]
     
18 to 44 years     47     54     101  
45 to 64 years     73     64     137  
>= 65 years     11     16     27  
Gender  
[units: participants]
     
Female     102     110     212  
Male     29     24     53  



  Outcome Measures
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1.  Primary:   Categorized Change From Baseline in 6-Minute Walking Distance   [ Time Frame: 1 Year, 2 Year, 3 Year ]

2.  Secondary:   Survival Status   [ Time Frame: 1, 2, 3, 4, and 5 years ]

3.  Secondary:   Change in Pulmonary Hypertension Criteria for Functional Capacity and Therapeutic Class   [ Time Frame: 1 Year, 2 Year, 3 Year ]

4.  Secondary:   Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36)   [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

5.  Secondary:   Change From Baseline in European Quality of Life Scale (EuroQol) 5-Dimensions (EQ-5D): Utility Index Score   [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

6.  Secondary:   Change From Baseline in European Quality of Life (EuroQol) Visual Analogue Scale (EQ-5D VAS): Current Health State Score   [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

7.  Secondary:   Change From Baseline in Medical Outcomes Study Short Form 36 (SF-36): Reported Health Transition Score   [ Time Frame: Baseline, Month 15, Month 27, Month 39 ]

8.  Secondary:   Change From Baseline in BORG Dyspnea Score   [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, Month 12, Month 15, Month 18, Month 21, Month 24, Month 27, Month 30, Month 33, Month 36 ]

9.  Other Pre-specified:   Change in Epoprostenol Dose From Baseline Maintained for 6 Months   [ Time Frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Month 9, and at 3-month intervals through Month 69 ]


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description The same event may appear as both an adverse event and a serious adverse event. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study.

Frequency Threshold
Threshold above which other adverse events are reported   0%  

Reporting Groups
  Description
Placebo/Sildenafil Core Study (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration): Placebo; Extension Study (until last enrolled subject completed 3 years of treatment): Sildenafil - initial dose 20 mg TID (3 times daily), may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Sildenafil/Sildenafil Core Study (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration): Sildenafil 20, 40, or 80 mg TID (3 times daily) based on toleration; Extension Study (until last enrolled subject completed 3 years of treatment): Sildenafil - initial dose 20 mg TID, may have been increased to 40 mg TID or 80 mg TID at discretion of Investigator
Placebo/Discontinued Core Study (16 weeks, or at least 4 weeks for subjects who required a change in epoprostenol dose due to clinical deterioration): Placebo; Extension Study (until last enrolled subject completed 3 years of treatment): Discontinued

Other Adverse Events
    Placebo/Sildenafil     Sildenafil/Sildenafil     Placebo/Discontinued  
Total, other (not including serious) adverse events        
# participants affected / at risk     115/115     134/134     15/16  
Blood and lymphatic system disorders        
Anaemia † 1      
# participants affected / at risk     23/115 (20.00%)     17/134 (12.69%)     0/16 (0.00%)  
Coagulopathy † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Febrile neutropenia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hilar lymphadenopathy † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Iron deficiency anaemia † 1      
# participants affected / at risk     4/115 (3.48%)     7/134 (5.22%)     0/16 (0.00%)  
Leukocytosis † 1      
# participants affected / at risk     3/115 (2.61%)     1/134 (0.75%)     0/16 (0.00%)  
Leukopenia † 1      
# participants affected / at risk     3/115 (2.61%)     1/134 (0.75%)     0/16 (0.00%)  
Lymphadenopathy † 1      
# participants affected / at risk     7/115 (6.09%)     2/134 (1.49%)     0/16 (0.00%)  
Lymphopenia † 1      
# participants affected / at risk     3/115 (2.61%)     5/134 (3.73%)     0/16 (0.00%)  
Microcytic anaemia † 1      
# participants affected / at risk     0/115 (0.00%)     4/134 (2.99%)     0/16 (0.00%)  
Neutropenia † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Normochromic normocytic anaemia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pancytopenia † 1      
# participants affected / at risk     3/115 (2.61%)     2/134 (1.49%)     0/16 (0.00%)  
Paratracheal lymphadenopathy † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Polycythaemia † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Splenic granuloma † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Splenomegaly † 1      
# participants affected / at risk     3/115 (2.61%)     4/134 (2.99%)     0/16 (0.00%)  
Thrombocytopenia † 1      
# participants affected / at risk     17/115 (14.78%)     10/134 (7.46%)     0/16 (0.00%)  
Cardiac disorders        
Angina pectoris † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Arrhythmia † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Arrhythmia supraventricular † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Atrial fibrillation † 1      
# participants affected / at risk     4/115 (3.48%)     3/134 (2.24%)     0/16 (0.00%)  
Bradycardia † 1      
# participants affected / at risk     3/115 (2.61%)     2/134 (1.49%)     0/16 (0.00%)  
Bundle branch block right † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiac disorder † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Cardiac failure † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiac failure chronic † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiac failure congestive † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiac failure high output † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiac flutter † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     1/16 (6.25%)  
Cardiac valve vegetation † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiogenic shock † 1      
# participants affected / at risk     0/115 (0.00%)     0/134 (0.00%)     1/16 (6.25%)  
Cardiomegaly † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiomyopathy † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Coronary artery disease † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Cyanosis † 1      
# participants affected / at risk     2/115 (1.74%)     4/134 (2.99%)     0/16 (0.00%)  
Extrasystoles † 1      
# participants affected / at risk     1/115 (0.87%)     3/134 (2.24%)     0/16 (0.00%)  
Hepatojugular reflux † 1      
# participants affected / at risk     3/115 (2.61%)     1/134 (0.75%)     0/16 (0.00%)  
Palpitations † 1      
# participants affected / at risk     33/115 (28.70%)     32/134 (23.88%)     0/16 (0.00%)  
Pericardial cyst † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Pericardial effusion † 1      
# participants affected / at risk     3/115 (2.61%)     7/134 (5.22%)     0/16 (0.00%)  
Pulmonary valve disease † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pulmonary valve incompetence † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Right ventricular failure † 1      
# participants affected / at risk     6/115 (5.22%)     3/134 (2.24%)     0/16 (0.00%)  
Right ventricular hypertrophy † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Supraventricular extrasystoles † 1      
# participants affected / at risk     0/115 (0.00%)     3/134 (2.24%)     0/16 (0.00%)  
Supraventricular tachycardia † 1      
# participants affected / at risk     4/115 (3.48%)     3/134 (2.24%)     0/16 (0.00%)  
Tachyarrhythmia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Tachycardia † 1      
# participants affected / at risk     9/115 (7.83%)     10/134 (7.46%)     0/16 (0.00%)  
Tricuspid valve incompetence † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Ventricular extrasystoles † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Ventricular tachycardia † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Congenital, familial and genetic disorders        
Colour blindness † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Gastrointestinal arteriovenous malformation † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Ear and labyrinth disorders        
Deafness † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Deafness neurosensory † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Ear disorder † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Ear haemorrhage † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Ear pain † 1      
# participants affected / at risk     4/115 (3.48%)     2/134 (1.49%)     0/16 (0.00%)  
Ear pruritus † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Hearing impaired † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Hypoacusis † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Tinnitus † 1      
# participants affected / at risk     3/115 (2.61%)     3/134 (2.24%)     0/16 (0.00%)  
Vertigo † 1      
# participants affected / at risk     9/115 (7.83%)     9/134 (6.72%)     0/16 (0.00%)  
Vertigo positional † 1      
# participants affected / at risk     0/115 (0.00%)     3/134 (2.24%)     0/16 (0.00%)  
Endocrine disorders        
Adrenal cyst † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Adrenal mass † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Autoimmune thyroiditis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Basedow's disease † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Goitre † 1      
# participants affected / at risk     1/115 (0.87%)     6/134 (4.48%)     0/16 (0.00%)  
Growth hormone deficiency † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Hyperadrenalism † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hyperprolactinaemia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hyperthyroidism † 1      
# participants affected / at risk     3/115 (2.61%)     5/134 (3.73%)     0/16 (0.00%)  
Hypopituitarism † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Hypothalamo-pituitary disorder † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hypothyroidism † 1      
# participants affected / at risk     4/115 (3.48%)     3/134 (2.24%)     0/16 (0.00%)  
Thyroid disorder † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Thyroiditis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Toxic nodular goitre † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Eye disorders        
Abnormal sensation in eye † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Blepharitis † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Cataract † 1      
# participants affected / at risk     3/115 (2.61%)     2/134 (1.49%)     0/16 (0.00%)  
Chalazion † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Choroidal detachment † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Chromatopsia † 1      
# participants affected / at risk     1/115 (0.87%)     4/134 (2.99%)     0/16 (0.00%)  
Conjunctival haemorrhage † 1      
# participants affected / at risk     4/115 (3.48%)     1/134 (0.75%)     0/16 (0.00%)  
Conjunctival hyperaemia † 1      
# participants affected / at risk     2/115 (1.74%)     3/134 (2.24%)     0/16 (0.00%)  
Conjunctivitis † 1      
# participants affected / at risk     1/115 (0.87%)     3/134 (2.24%)     0/16 (0.00%)  
Cyanopsia † 1      
# participants affected / at risk     2/115 (1.74%)     4/134 (2.99%)     0/16 (0.00%)  
Diabetic retinopathy † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Diplopia † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Dry eye † 1      
# participants affected / at risk     1/115 (0.87%)     4/134 (2.99%)     0/16 (0.00%)  
Eye disorder † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Eye haemorrhage † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Eye inflammation † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Eye irritation † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Eye oedema † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Eye pain † 1      
# participants affected / at risk     2/115 (1.74%)     3/134 (2.24%)     0/16 (0.00%)  
Eye pruritus † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Eye swelling † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Eyelid oedema † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Keratitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Lacrimation increased † 1      
# participants affected / at risk     3/115 (2.61%)     1/134 (0.75%)     0/16 (0.00%)  
Myodesopsia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Myopia † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Night blindness † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Ocular hyperaemia † 1      
# participants affected / at risk     2/115 (1.74%)     5/134 (3.73%)     0/16 (0.00%)  
Ocular icterus † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Photophobia † 1      
# participants affected / at risk     6/115 (5.22%)     4/134 (2.99%)     0/16 (0.00%)  
Photopsia † 1      
# participants affected / at risk     1/115 (0.87%)     3/134 (2.24%)     0/16 (0.00%)  
Presbyopia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Retinal degeneration † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Retinal disorder † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Retinal haemorrhage † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Scleritis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Venous stasis retinopathy † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Vision blurred † 1      
# participants affected / at risk     9/115 (7.83%)     11/134 (8.21%)     0/16 (0.00%)  
Visual acuity reduced † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Visual brightness † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Visual impairment † 1      
# participants affected / at risk     3/115 (2.61%)     6/134 (4.48%)     0/16 (0.00%)  
Xanthopsia † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Xerophthalmia † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Gastrointestinal disorders        
Abdominal discomfort † 1      
# participants affected / at risk     7/115 (6.09%)     5/134 (3.73%)     0/16 (0.00%)  
Abdominal distension † 1      
# participants affected / at risk     15/115 (13.04%)     13/134 (9.70%)     0/16 (0.00%)  
Abdominal hernia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Abdominal pain † 1      
# participants affected / at risk     13/115 (11.30%)     22/134 (16.42%)     3/16 (18.75%)  
Abdominal pain lower † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Abdominal pain upper † 1      
# participants affected / at risk     17/115 (14.78%)     13/134 (9.70%)     0/16 (0.00%)  
Abdominal tenderness † 1      
# participants affected / at risk     0/115 (0.00%)     0/134 (0.00%)     1/16 (6.25%)  
Anal inflammation † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Anal pruritus † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Aphthous stomatitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Ascites † 1      
# participants affected / at risk     18/115 (15.65%)     12/134 (8.96%)     1/16 (6.25%)  
Barrett's oesophagus † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Breath odour † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Colitis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Colitis ulcerative † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Colonic polyp † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Constipation † 1      
# participants affected / at risk     7/115 (6.09%)     11/134 (8.21%)     1/16 (6.25%)  
Dental caries † 1      
# participants affected / at risk     3/115 (2.61%)     0/134 (0.00%)     0/16 (0.00%)  
Diarrhoea † 1      
# participants affected / at risk     54/115 (46.96%)     64/134 (47.76%)     5/16 (31.25%)  
Diverticulum † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Diverticulum intestinal † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Dry mouth † 1      
# participants affected / at risk     9/115 (7.83%)     11/134 (8.21%)     0/16 (0.00%)  
Duodenitis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Dyspepsia † 1      
# participants affected / at risk     20/115 (17.39%)     32/134 (23.88%)     0/16 (0.00%)  
Dysphagia † 1      
# participants affected / at risk     4/115 (3.48%)     0/134 (0.00%)     0/16 (0.00%)  
Enterocolitis haemorrhagic † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Epigastric discomfort † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Flatulence † 1      
# participants affected / at risk     3/115 (2.61%)     3/134 (2.24%)     0/16 (0.00%)  
Gastric disorder † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Gastritis † 1      
# participants affected / at risk     6/115 (5.22%)     5/134 (3.73%)     0/16 (0.00%)  
Gastritis erosive † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Gastrointestinal haemorrhage † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Gastrointestinal motility disorder † 1      
# participants affected / at risk     3/115 (2.61%)     0/134 (0.00%)     0/16 (0.00%)  
Gastrointestinal pain † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Gastrointestinal telangiectasia † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Gastrooesophageal reflux disease † 1      
# participants affected / at risk     11/115 (9.57%)     13/134 (9.70%)     0/16 (0.00%)  
Gingival bleeding † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Gingival pain † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Gingivitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Glossitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Glossodynia † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Haematemesis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Haematochezia † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Haemorrhoidal haemorrhage † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Haemorrhoids † 1      
# participants affected / at risk     2/115 (1.74%)     3/134 (2.24%)     0/16 (0.00%)  
Hiatus hernia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hyperchlorhydria † 1      
# participants affected / at risk     1/115 (0.87%)     3/134 (2.24%)     0/16 (0.00%)  
Hypoaesthesia oral † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Ileus † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Impaired gastric emptying † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Inguinal hernia † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Intestinal functional disorder † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Irritable bowel syndrome † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Leukoplakia oral † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Lower gastrointestinal haemorrhage † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Melaena † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Mouth ulceration † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Nausea † 1      
# participants affected / at risk     48/115 (41.74%)     63/134 (47.01%)     4/16 (25.00%)  
Odynophagia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Oesophageal dilatation † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Oesophageal disorder † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Oesophageal hypomotility † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Oesophageal pain † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Oesophageal ulcer † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Oesophagitis † 1      
# participants affected / at risk     5/115 (4.35%)     2/134 (1.49%)     0/16 (0.00%)  
Oral disorder † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Oral pain † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pancreatic calcification † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pancreatic cyst † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Pancreatic disorder † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pancreatic mass † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pancreatitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Pancreatitis chronic † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Polyp colorectal † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Rectal haemorrhage † 1      
# participants affected / at risk     3/115 (2.61%)     3/134 (2.24%)     0/16 (0.00%)  
Rectal prolapse † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Reflux oesophagitis † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Retching † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Salivary duct obstruction † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Salivary hypersecretion † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Tongue discolouration † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Toothache † 1      
# participants affected / at risk     2/115 (1.74%)     3/134 (2.24%)     0/16 (0.00%)  
Umbilical hernia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Upper gastrointestinal haemorrhage † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Varices oesophageal † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Vomiting † 1      
# participants affected / at risk     31/115 (26.96%)     41/134 (30.60%)     2/16 (12.50%)  
Vomiting projectile † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
General disorders        
Abasia † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Asthenia † 1      
# participants affected / at risk     13/115 (11.30%)     21/134 (15.67%)     1/16 (6.25%)  
Catheter related complication † 1      
# participants affected / at risk     11/115 (9.57%)     10/134 (7.46%)     0/16 (0.00%)  
Catheter site discharge † 1      
# participants affected / at risk     6/115 (5.22%)     6/134 (4.48%)     0/16 (0.00%)  
Catheter site erosion † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Catheter site erythema † 1      
# participants affected / at risk     3/115 (2.61%)     6/134 (4.48%)     0/16 (0.00%)  
Catheter site haematoma † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Catheter site haemorrhage † 1      
# participants affected / at risk     4/115 (3.48%)     7/134 (5.22%)     0/16 (0.00%)  
Catheter site inflammation † 1      
# participants affected / at risk     4/115 (3.48%)     1/134 (0.75%)     0/16 (0.00%)  
Catheter site oedema † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Catheter site pain † 1      
# participants affected / at risk     3/115 (2.61%)     4/134 (2.99%)     0/16 (0.00%)  
Catheter site rash † 1      
# participants affected / at risk     0/115 (0.00%)     3/134 (2.24%)     0/16 (0.00%)  
Catheter site related reaction † 1      
# participants affected / at risk     2/115 (1.74%)     4/134 (2.99%)     0/16 (0.00%)  
Catheter thrombosis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Chest discomfort † 1      
# participants affected / at risk     10/115 (8.70%)     13/134 (9.70%)     1/16 (6.25%)  
Chest pain † 1      
# participants affected / at risk     26/115 (22.61%)     36/134 (26.87%)     0/16 (0.00%)  
Chills † 1      
# participants affected / at risk     7/115 (6.09%)     11/134 (8.21%)     0/16 (0.00%)  
Discomfort † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Early satiety † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Energy increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Exercise tolerance decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Face oedema † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Fatigue † 1      
# participants affected / at risk     44/115 (38.26%)     56/134 (41.79%)     4/16 (25.00%)  
Feeling cold † 1      
# participants affected / at risk     5/115 (4.35%)     2/134 (1.49%)     0/16 (0.00%)  
Feeling hot † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Feeling jittery † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Gait disturbance † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
General physical health deterioration † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Generalised oedema † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Hyperthermia † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Hypothermia † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Ill-defined disorder † 1      
# participants affected / at risk     3/115 (2.61%)     1/134 (0.75%)     0/16 (0.00%)  
Implant site discharge † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Implant site reaction † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Implant site ulcer † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Inflammation † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Influenza like illness † 1      
# participants affected / at risk     7/115 (6.09%)     2/134 (1.49%)     0/16 (0.00%)  
Infusion site induration † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Infusion site pain † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Infusion site reaction † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Infusion site vesicles † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Injection site pain † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Irritability † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Malaise † 1      
# participants affected / at risk     5/115 (4.35%)     8/134 (5.97%)     0/16 (0.00%)  
Mass † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Mucosal inflammation † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Oedema † 1      
# participants affected / at risk     16/115 (13.91%)     25/134 (18.66%)     1/16 (6.25%)  
Oedema peripheral † 1      
# participants affected / at risk     37/115 (32.17%)     38/134 (28.36%)     1/16 (6.25%)  
Pain † 1      
# participants affected / at risk     11/115 (9.57%)     12/134 (8.96%)     1/16 (6.25%)  
Pitting oedema † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pyrexia † 1      
# participants affected / at risk     23/115 (20.00%)     16/134 (11.94%)     0/16 (0.00%)  
Sensation of blood flow † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Sensation of foreign body † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Temperature intolerance † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Tenderness † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Thirst † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Unevaluable event † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hepatobiliary disorders        
Autoimmune hepatitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Bile duct stenosis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Cholecystitis acute † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Cholelithiasis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Chronic hepatic failure † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Gallbladder disorder † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Hepatic cirrhosis † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     1/16 (6.25%)  
Hepatic congestion † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hepatic cyst † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Hepatic lesion † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hepatic pain † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Hepatomegaly † 1      
# participants affected / at risk     5/115 (4.35%)     13/134 (9.70%)     2/16 (12.50%)  
Hepatosplenomegaly † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Jaundice † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Portal hypertension † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Immune system disorders        
Drug hypersensitivity † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Hypersensitivity † 1      
# participants affected / at risk     0/115 (0.00%)     3/134 (2.24%)     0/16 (0.00%)  
Multiple allergies † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Seasonal allergy † 1      
# participants affected / at risk     3/115 (2.61%)     2/134 (1.49%)     0/16 (0.00%)  
Infections and infestations        
Abscess † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Acute sinusitis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Bacteraemia † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Bacterial infection † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Body tinea † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Bronchitis † 1      
# participants affected / at risk     15/115 (13.04%)     24/134 (17.91%)     0/16 (0.00%)  
Bronchopneumonia † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Candidiasis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     1/16 (6.25%)  
Catheter related infection † 1      
# participants affected / at risk     18/115 (15.65%)     18/134 (13.43%)     0/16 (0.00%)  
Catheter sepsis † 1      
# participants affected / at risk     4/115 (3.48%)     1/134 (0.75%)     0/16 (0.00%)  
Catheter site cellulitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Catheter site infection † 1      
# participants affected / at risk     14/115 (12.17%)     6/134 (4.48%)     0/16 (0.00%)  
Cellulitis † 1      
# participants affected / at risk     6/115 (5.22%)     6/134 (4.48%)     0/16 (0.00%)  
Central line infection † 1      
# participants affected / at risk     9/115 (7.83%)     9/134 (6.72%)     0/16 (0.00%)  
Chronic sinusitis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Clostridium difficile colitis † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Conjunctivitis infective † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Conjunctivitis viral † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Cystitis † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Dacryocanaliculitis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Device related infection † 1      
# participants affected / at risk     3/115 (2.61%)     2/134 (1.49%)     0/16 (0.00%)  
Diverticulitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Ear infection † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     1/16 (6.25%)  
Ear lobe infection † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Erysipelas † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Eye infection † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Eye infection bacterial † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Fungal infection † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Furuncle † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Gastroenteritis † 1      
# participants affected / at risk     5/115 (4.35%)     8/134 (5.97%)     0/16 (0.00%)  
Gastroenteritis viral † 1      
# participants affected / at risk     6/115 (5.22%)     3/134 (2.24%)     0/16 (0.00%)  
Genital herpes † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Helicobacter infection † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Hepatitis A † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Herpes simplex † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Herpes zoster † 1      
# participants affected / at risk     6/115 (5.22%)     4/134 (2.99%)     0/16 (0.00%)  
Hordeolum † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Infected sebaceous cyst † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Infection † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Influenza † 1      
# participants affected / at risk     13/115 (11.30%)     15/134 (11.19%)     0/16 (0.00%)  
Injection site infection † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Localised infection † 1      
# participants affected / at risk     5/115 (4.35%)     3/134 (2.24%)     0/16 (0.00%)  
Lower respiratory tract infection † 1      
# participants affected / at risk     3/115 (2.61%)     2/134 (1.49%)     0/16 (0.00%)  
Lung infection † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Lymphangitis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Moraxella infection † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Nasopharyngitis † 1      
# participants affected / at risk     21/115 (18.26%)     18/134 (13.43%)     1/16 (6.25%)  
Onychomycosis † 1      
# participants affected / at risk     1/115 (0.87%)     3/134 (2.24%)     0/16 (0.00%)  
Oral candidiasis † 1      
# participants affected / at risk     6/115 (5.22%)     2/134 (1.49%)     0/16 (0.00%)  
Oral fungal infection † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Oral herpes † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Otitis externa † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Otitis media † 1      
# participants affected / at risk     2/115 (1.74%)     6/134 (4.48%)     0/16 (0.00%)  
Parotitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Periorbital infection † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Pharyngitis † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Pharyngitis bacterial † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Pharyngitis streptococcal † 1      
# participants affected / at risk     2/115 (1.74%)     4/134 (2.99%)     0/16 (0.00%)  
Pneumonia † 1      
# participants affected / at risk     6/115 (5.22%)     3/134 (2.24%)     1/16 (6.25%)  
Pulmonary mycosis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Rash pustular † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Respiratory tract infection † 1      
# participants affected / at risk     5/115 (4.35%)     4/134 (2.99%)     0/16 (0.00%)  
Respiratory tract infection viral † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Rhinitis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Sepsis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     1/16 (6.25%)  
Septic embolus † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     1/16 (6.25%)  
Sinusitis † 1      
# participants affected / at risk     16/115 (13.91%)     17/134 (12.69%)     0/16 (0.00%)  
Skin infection † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Sputum purulent † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Staphylococcal infection † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Subcutaneous abscess † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Tonsillitis † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Tooth abscess † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Tooth infection † 1      
# participants affected / at risk     0/115 (0.00%)     3/134 (2.24%)     0/16 (0.00%)  
Tracheitis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Upper respiratory tract infection † 1      
# participants affected / at risk     39/115 (33.91%)     54/134 (40.30%)     1/16 (6.25%)  
Urethritis † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Urinary tract infection † 1      
# participants affected / at risk     12/115 (10.43%)     11/134 (8.21%)     0/16 (0.00%)  
Viral infection † 1      
# participants affected / at risk     3/115 (2.61%)     3/134 (2.24%)     0/16 (0.00%)  
Viral upper respiratory tract infection † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Vulvovaginal candidiasis † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Vulvovaginal mycotic infection † 1      
# participants affected / at risk     3/115 (2.61%)     3/134 (2.24%)     0/16 (0.00%)  
Injury, poisoning and procedural complications        
Accidental exposure † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Accidental overdose † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Ankle fracture † 1      
# participants affected / at risk     0/115 (0.00%)     3/134 (2.24%)     0/16 (0.00%)  
Arthropod bite † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Chest injury † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Chillblains † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Contusion † 1      
# participants affected / at risk     8/115 (6.96%)     14/134 (10.45%)     0/16 (0.00%)  
Corneal abrasion † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Device breakage † 1      
# participants affected / at risk     1/115 (0.87%)     7/134 (5.22%)     0/16 (0.00%)  
Device failure † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Device malfunction † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Device migration † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Drug exposure during pregnancy † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Drug toxicity † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Excoriation † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Eye injury † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Face injury † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Fall † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Foot fracture † 1      
# participants affected / at risk     2/115 (1.74%)     3/134 (2.24%)     0/16 (0.00%)  
Fractured coccyx † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Hand fracture † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Head injury † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Hip fracture † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Humerus fracture † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Incision site erythema † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Incision site pain † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Incorrect dose administered † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Injury † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Joint dislocation † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Joint injury † 1      
# participants affected / at risk     2/115 (1.74%)     4/134 (2.99%)     0/16 (0.00%)  
Joint sprain † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Ligament rupture † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Limb injury † 1      
# participants affected / at risk     4/115 (3.48%)     1/134 (0.75%)     0/16 (0.00%)  
Lumbar vertebral fracture † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Medical device complication † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Meniscus lesion † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Mouth injury † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Muscle strain † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Pelvic fracture † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Periorbital haematoma † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Post procedural complication † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Post procedural haemorrhage † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Procedural complication † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Procedural pain † 1      
# participants affected / at risk     3/115 (2.61%)     2/134 (1.49%)     0/16 (0.00%)  
Rib fracture † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Road traffic accident † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Scratch † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Skeletal injury † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Skin laceration † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Sunburn † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Therapeutic agent toxicity † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Thermal burn † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Thoracic vertebral fracture † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Tibia fracture † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Tooth fracture † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Transfusion reaction † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Wound † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Wrist fracture † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Investigations        
Alanine aminotransferase increased † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Antinuclear antibody positive † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Aspartate aminotransferase increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Biopsy lymph gland † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood albumin decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood albumin increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Blood alkaline phosphatase increased † 1      
# participants affected / at risk     0/115 (0.00%)     3/134 (2.24%)     0/16 (0.00%)  
Blood bicarbonate decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood bilirubin increased † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Blood calcium decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Blood creatinine increased † 1      
# participants affected / at risk     5/115 (4.35%)     3/134 (2.24%)     0/16 (0.00%)  
Blood culture positive † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Blood folate decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Blood glucose decreased † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Blood glucose increased † 1      
# participants affected / at risk     3/115 (2.61%)     1/134 (0.75%)     0/16 (0.00%)  
Blood iron decreased † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Blood magnesium decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Blood phosphorus decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood potassium decreased † 1      
# participants affected / at risk     3/115 (2.61%)     5/134 (3.73%)     0/16 (0.00%)  
Blood potassium increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood pressure decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood pressure diastolic decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood pressure increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood pressure systolic decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Blood prolactin decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood sodium decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Blood sodium increased † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
Blood thyroid stimulating hormone increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Blood urea increased † 1      
# participants affected / at risk     3/115 (2.61%)     5/134 (3.73%)     0/16 (0.00%)  
Blood uric acid increased † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Blood urine present † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Body temperature increased † 1      
# participants affected / at risk     2/115 (1.74%)     2/134 (1.49%)     0/16 (0.00%)  
Brain natriuretic peptide increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Breath sounds abnormal † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Carbon dioxide decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiac index decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Cardiac murmur † 1      
# participants affected / at risk     6/115 (5.22%)     3/134 (2.24%)     0/16 (0.00%)  
Cardiac output increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Cardioactive drug level below therapeutic † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Cardioactive drug level decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Cardioactive drug level increased † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Catheterisation cardiac abnormal † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Chest X-ray abnormal † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Coagulation test abnormal † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Coagulation time prolonged † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Computerised tomogram abdomen abnormal † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Computerised tomogram thorax abnormal † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Drug level increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Electrocardiogram change † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Exercise test abnormal † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Gallop rhythm present † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Gamma-glutamyltransferase increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Haematocrit increased † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Haemoglobin decreased † 1      
# participants affected / at risk     4/115 (3.48%)     1/134 (0.75%)     0/16 (0.00%)  
Haemoglobin increased † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Heart rate decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Heart rate increased † 1      
# participants affected / at risk     0/115 (0.00%)     4/134 (2.99%)     0/16 (0.00%)  
Heart rate irregular † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Heart sounds abnormal † 1      
# participants affected / at risk     3/115 (2.61%)     1/134 (0.75%)     0/16 (0.00%)  
Helicobacter pylori identification test positive † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Hepatic enzyme increased † 1      
# participants affected / at risk     2/115 (1.74%)     0/134 (0.00%)     0/16 (0.00%)  
International normalised ratio decreased † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
International normalised ratio increased † 1      
# participants affected / at risk     8/115 (6.96%)     13/134 (9.70%)     0/16 (0.00%)  
Intraocular pressure increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Lipase increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Liver function test abnormal † 1      
# participants affected / at risk     2/115 (1.74%)     3/134 (2.24%)     0/16 (0.00%)  
Liver scan abnormal † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Low density lipoprotein increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Lymphocyte count decreased † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Mean cell haemoglobin decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Mean cell volume decreased † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Medical observation † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Neutrophil count increased † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Occult blood † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Occult blood positive † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Oxygen consumption increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Oxygen saturation decreased † 1      
# participants affected / at risk     2/115 (1.74%)     4/134 (2.99%)     0/16 (0.00%)  
Platelet count decreased † 1      
# participants affected / at risk     6/115 (5.22%)     2/134 (1.49%)     0/16 (0.00%)  
Platelet function test abnormal † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Protein total decreased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Protein total increased † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
Protein urine † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Protein urine present † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pulmonary arterial pressure increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Pulmonary arterial wedge pressure increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pulmonary function challenge test abnormal † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Pulse pressure decreased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Red blood cell count increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Red cell distribution width increased † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Smear cervix abnormal † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Spleen scan abnormal † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Sputum culture positive † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Thyroid function test abnormal † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Thyroxine † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Thyroxine increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Transaminases increased † 1      
# participants affected / at risk     1/115 (0.87%)     0/134 (0.00%)     0/16 (0.00%)  
Urine output decreased † 1      
# participants affected / at risk     1/115 (0.87%)     3/134 (2.24%)     0/16 (0.00%)  
Venous pressure jugular increased † 1      
# participants affected / at risk     5/115 (4.35%)     3/134 (2.24%)     0/16 (0.00%)  
Weight decreased † 1      
# participants affected / at risk     15/115 (13.04%)     15/134 (11.19%)     0/16 (0.00%)  
Weight increased † 1      
# participants affected / at risk     15/115 (13.04%)     11/134 (8.21%)     1/16 (6.25%)  
White blood cell count decreased † 1      
# participants affected / at risk     0/115 (0.00%)     2/134 (1.49%)     0/16 (0.00%)  
White blood cell count increased † 1      
# participants affected / at risk     1/115 (0.87%)     2/134 (1.49%)     0/16 (0.00%)  
Metabolism and nutrition disorders        
Acidosis † 1      
# participants affected / at risk     1/115 (0.87%)     1/134 (0.75%)     0/16 (0.00%)  
Anorexia † 1      
# participants affected / at risk     10/115 (8.70%)     18/134 (13.43%)     1/16 (6.25%)  
Cachexia † 1      
# participants affected / at risk     0/115 (0.00%)     3/134 (2.24%)     0/16 (0.00%)  
Decreased appetite † 1      
# participants affected / at risk     5/115 (4.35%)     8/134 (5.97%)     0/16 (0.00%)  
Dehydration † 1      
# participants affected / at risk     2/115 (1.74%)     4/134 (2.99%)     0/16 (0.00%)  
Diabetes mellitus † 1      
# participants affected / at risk     2/115 (1.74%)     1/134 (0.75%)     0/16 (0.00%)  
Diabetes mellitus inadequate control † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Electrolyte imbalance † 1      
# participants affected / at risk     0/115 (0.00%)     1/134 (0.75%)     0/16 (0.00%)  
Fluid overload † 1      
# participants affected / at risk     1/115 (0.87%)     3/134 (2.24%)     0/16 (0.00%)  
Fluid retention † 1      
# participants affected / at risk     1/115 (0.87%)     4/134 (2.99%)     0/16 (0.00%)  
Gout † 1      
# participants affected / at risk     7/115 (6.09%)     3/134 (2.24%)     0/16 (0.00%)