A Study To Assess The Safety And Efficacy Of SU11248 In Patients With Gastrointestinal Stromal Tumor(GIST)

This study has been completed.
Sponsor:
Information provided by:
Pfizer
ClinicalTrials.gov Identifier:
NCT00075218
First received: January 6, 2004
Last updated: August 31, 2009
Last verified: August 2009
Results First Received: May 6, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Gastrointestinal Stromal Tumor
Interventions: Drug: Placebo
Drug: SU011248

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Enrollment began (medical clinic) in December 2003. Study was unblinded on 27 January 2005 (end of Double-blind treatment). Subjects experiencing disease progression could crossover to Open-label treatment. Open-label data collection ended May 2008.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

361 subjects randomized to double-blind treatment in 2:1 ratio (sunitinib vs. Placebo).

255 subjects continued on or crossed over to Open-label treatment.


Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Sunitinib Open-Label Treatment Subjects experiencing disease progression could have their treatment assignment unblinded, and subjects who had been receiving placebo could crossover to open-label treatment with sunitinib; subjects who had been receiving sunitinib during double-blind treatment of the study could continue to do so after unblinding if, in the opinion of the investigator, there was sufficient evidence of clinical benefit.

Participant Flow for 2 periods

Period 1:   Double-Blind Treatment
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Sunitinib Open-Label Treatment  
STARTED     243 [1]   118 [1]   0  
Received Double-Blind Treatment     228 [2]   114 [2]   0  
Crossed Over to Open-Label Treatment     152     103     0  
COMPLETED     152 [3]   103 [3]   0  
NOT COMPLETED     91     15     0  
Adverse Event                 23                 4                 0  
Withdrawal by Subject                 7                 4                 0  
Lost to Follow-up                 1                 0                 0  
Lack of Efficacy                 58                 6                 0  
Decision of Sponsor                 0                 1                 0  
No study medication taken                 2                 0                 0  
[1] Intent To Treat Population (ITT)
[2] As Treated Population (AT)
[3] Defined:subjects completed double-blind treatment phase and/or entered open-label treatment phase.

Period 2:   Open-Label Treatment
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Sunitinib Open-Label Treatment  
STARTED     0     0     255  
COMPLETED     0     0     0  
NOT COMPLETED     0     0     255  
Lack of Efficacy                 0                 0                 174  
Adverse Event                 0                 0                 51  
Withdrawal by Subject                 0                 0                 12  
Decision of Sponsor                 0                 0                 8  
Protocol Violation                 0                 0                 1  
enrolled in a separate continuation                 0                 0                 9  



  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
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Total Total of all reporting groups

Baseline Measures
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Total  
Number of Participants  
[units: participants]
  243     118     361  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     170     81     251  
>=65 years     73     37     110  
Gender  
[units: participants]
     
Female     91     71     162  
Male     152     47     199  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Time to Tumor Progression (TTP) as Assessed by Imaging Studies at End of Double-blind Treatment Phase   [ Time Frame: Day 28 of each 6-week cycle : duration of double-blind treatment phase ]

2.  Primary:   Time to Tumor Progression (TTP) as Assessed in the Double-blind Treatment Phase at End of Study   [ Time Frame: Day 28 of each 6-week cycle : duration of double-blind treatment phase after Last Subject Last Visit (LSLV) ]

3.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

4.  Secondary:   Overall Survival Status of Subjects   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

5.  Secondary:   Overall Survival   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

6.  Secondary:   Overall Survival Based on the Rank Preserving Structural Failure Time Method   [ Time Frame: clinic visit or telephone contact every 2 months for up to 3 years from the last dose of study drug ]

7.  Secondary:   Best Overall Tumor Response During Double-blind Treatment Phase   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

8.  Secondary:   Confirmed Objective Response (CR or PR) in Subjects   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

9.  Secondary:   Time to Tumor Response (TTR)   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

10.  Secondary:   Duration of Performance Status Maintenance   [ Time Frame: Day 28 of each cycle : duration of double-blind treatment phase ]

11.  Secondary:   Time to Pain Progression Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

12.  Secondary:   Subjects With Pain Relief Response Using McGill Pain Questionnaire-present Pain Intensity (MPQ-PPI)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

13.  Secondary:   Change From Baseline Score in EuroQoL Visual Analog Scale (EQ-VAS)   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]

14.  Secondary:   Change From Baseline in EQ-5D Health State Profile Index   [ Time Frame: Day 1 & 28 of each cycle : duration of double-blind treatment phase ]


  Serious Adverse Events


  Other Adverse Events
  Hide Other Adverse Events

Time Frame No text entered.
Additional Description No text entered.

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

Reporting Groups
  Description
Sunitinib Double-Blind Treatment Starting dose: 50 mg orally once daily as a single agent for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks. (Schedule 4/2). Subjects received best supportive care in addition to the study treatment.
Placebo Double-Blind Treatment Starting daily dose of 1 capsule, size- and color-matched to the sunitinib 50-mg capsule for 4 consecutive weeks followed by a 2-week off-treatment period to form a complete cycle of 6 weeks (Schedule 4/2). Subjects received best supportive care in addition to the study treatment. Subjects were provided the opportunity to receive open-label sunitinib at the time of confirmed disease progression or study unblinding.
Sunitinib Open-Label Treatment Subjects experiencing disease progression could have their treatment assignment unblinded, and subjects who had been receiving placebo could crossover to open-label treatment with sunitinib; subjects who had been receiving sunitinib during double-blind treatment of the study could continue to do so after unblinding if, in the opinion of the investigator, there was sufficient evidence of clinical benefit.

Other Adverse Events
    Sunitinib Double-Blind Treatment     Placebo Double-Blind Treatment     Sunitinib Open-Label Treatment  
Total, other (not including serious) adverse events        
# participants affected     223     110     254  
Blood and lymphatic system disorders        
Anaemia † 1      
# participants affected / at risk     46/228 (20.18%)     10/114 (8.77%)     80/255 (31.37%)  
Neutropenia      
# participants affected / at risk     33/228 (14.47%)     1/114 (0.88%)     64/255 (25.10%)  
Thrombocytopenia      
# participants affected / at risk     33/228 (14.47%)     1/114 (0.88%)     44/255 (17.25%)  
Leukopenia      
# participants affected / at risk     11/228 (4.82%)     1/114 (0.88%)     22/255 (8.63%)  
Lymphopenia      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     9/255 (3.53%)  
Febrile neutropenia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Hand and foot syndrome secondary to sickle cell anaemia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Lymphadenopathy      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Pancytopenia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Disseminated intravascular coagulation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Granulocytopenia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
haemolytic anaemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Leukocytosis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Cardiac disorders        
Ejection fraction decreased      
# participants affected / at risk     19/228 (8.33%)     3/114 (2.63%)     5/255 (1.96%)  
Left ventricular dysfunction      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     6/255 (2.35%)  
Tachycardia      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     4/255 (1.57%)  
Bradycardia      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     3/255 (1.18%)  
Cardiac disorder      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     0/255 (0.00%)  
Cardiomyopathy      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     1/255 (0.39%)  
Palpitations      
# participants affected / at risk     2/228 (0.88%)     2/114 (1.75%)     2/255 (0.78%)  
Angina pectoris      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Arrhythmia supraventricular      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Atrial fibrillation      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Cardiac arrest      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     0/255 (0.00%)  
Cardiac failure      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Cardiomegaly      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Electrocardiogram QT prolonged      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Left atrial dilatation      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Left ventricular failure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Mitral valve incompetence      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Pericardial effusion      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Sinus arrhythmia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Ventricular extrasystoles      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Bundle branch block left      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Sinus tachycardia      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Cardiac failure congestive      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Cardio-respiratory arrest      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Sinus bradycardia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Ventricular hypokinesia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Left ventricular hypertrophy      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Myocardial infarction      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Myocardial ischaemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Splinter haemorhages      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Supraventricular tachycardia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Ventricular dysfunction      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Congenital, familial and genetic disorders        
Pyloric stenosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Dermoid cyst      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Epidermolysis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hydrocele      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Ear and labyrinth disorders        
Ear discomfort      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Ear pain      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     3/255 (1.18%)  
Hypoacusis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Vertigo      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Tinnitus      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     3/255 (1.18%)  
Dysacusis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hearing impaired      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Endocrine disorders        
Hypothyroidism      
# participants affected / at risk     9/228 (3.95%)     1/114 (0.88%)     45/255 (17.65%)  
Adrenal insufficiency      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Cushingoid      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Hyperthyroidism      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Thyroid disorder      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Eye disorders        
Eye oedema      
# participants affected / at risk     5/228 (2.19%)     0/114 (0.00%)     5/255 (1.96%)  
Lacrimation increased      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     2/255 (0.78%)  
Vision blurred      
# participants affected / at risk     3/228 (1.32%)     1/114 (0.88%)     5/255 (1.96%)  
Conjunctival haemorrhage      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     0/255 (0.00%)  
Conjunctivitis      
# participants affected / at risk     2/228 (0.88%)     2/114 (1.75%)     6/255 (2.35%)  
Visual disturbance      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     4/255 (1.57%)  
Diplopia      
# participants affected / at risk     1/228 (0.44%)     2/114 (1.75%)     0/255 (0.00%)  
Eyelid oedema      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     9/255 (3.53%)  
Lacrimal disorder      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Photopsia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Vitreous floaters      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Eye pain      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Eye pruritus      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Dry eye      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Glaucoma      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Macular degeneration      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Orbital oedema      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Asthenopia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blepharitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Eye discharge      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Eye haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Eye irritation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Eye swelling      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Ocular hyperaemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Punctate keratitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Scleral haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Visual acuity reduced      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Gastrointestinal disorders        
Diarrhoea      
# participants affected / at risk     102/228 (44.74%)     21/114 (18.42%)     119/255 (46.67%)  
Abdominal pain      
# participants affected / at risk     82/228 (35.96%)     37/114 (32.46%)     106/255 (41.57%)  
Nausea      
# participants affected / at risk     80/228 (35.09%)     28/114 (24.56%)     114/255 (44.71%)  
Vomiting      
# participants affected / at risk     63/228 (27.63%)     23/114 (20.18%)     93/255 (36.47%)  
Constipation      
# participants affected / at risk     53/228 (23.25%)     22/114 (19.30%)     75/255 (29.41%)  
Dyspepsia      
# participants affected / at risk     45/228 (19.74%)     6/114 (5.26%)     56/255 (21.96%)  
Stomatitis      
# participants affected / at risk     37/228 (16.23%)     1/114 (0.88%)     44/255 (17.25%)  
Abdominal pain upper      
# participants affected / at risk     28/228 (12.28%)     10/114 (8.77%)     37/255 (14.51%)  
Dry mouth      
# participants affected / at risk     26/228 (11.40%)     4/114 (3.51%)     22/255 (8.63%)  
Flatulence      
# participants affected / at risk     24/228 (10.53%)     5/114 (4.39%)     26/255 (10.20%)  
Abdominal distension      
# participants affected / at risk     18/228 (7.89%)     9/114 (7.89%)     38/255 (14.90%)  
Oral pain      
# participants affected / at risk     16/228 (7.02%)     1/114 (0.88%)     30/255 (11.76%)  
Glossodynia      
# participants affected / at risk     13/228 (5.70%)     0/114 (0.00%)     20/255 (7.84%)  
Gastrooesophageal reflux disease      
# participants affected / at risk     10/228 (4.39%)     2/114 (1.75%)     23/255 (9.02%)  
Ascites      
# participants affected / at risk     9/228 (3.95%)     6/114 (5.26%)     9/255 (3.53%)  
Abdominal discomfort      
# participants affected / at risk     8/228 (3.51%)     0/114 (0.00%)     10/255 (3.92%)  
Rectal haemorrhage      
# participants affected / at risk     8/228 (3.51%)     2/114 (1.75%)     16/255 (6.27%)  
Mouth ulceration      
# participants affected / at risk     7/228 (3.07%)     0/114 (0.00%)     5/255 (1.96%)  
Dysphagia      
# participants affected / at risk     6/228 (2.63%)     1/114 (0.88%)     12/255 (4.71%)  
Gastritis      
# participants affected / at risk     4/228 (1.75%)     0/114 (0.00%)     3/255 (1.18%)  
Gingival pain      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     3/255 (1.18%)  
Haemorrhoids      
# participants affected / at risk     4/228 (1.75%)     2/114 (1.75%)     12/255 (4.71%)  
Oral discomfort      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     3/255 (1.18%)  
Abdominal pain lower      
# participants affected / at risk     3/228 (1.32%)     2/114 (1.75%)     8/255 (3.14%)  
Eructation      
# participants affected / at risk     3/228 (1.32%)     2/114 (1.75%)     5/255 (1.96%)  
Lip dry      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     2/255 (0.78%)  
Oesophagitis      
# participants affected / at risk     3/228 (1.32%)     1/114 (0.88%)     6/255 (2.35%)  
Oral mucosal discolouration      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     0/255 (0.00%)  
Proctalgia      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     7/255 (2.75%)  
Reflux oesophagitis      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     1/255 (0.39%)  
Retching      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     2/255 (0.78%)  
Salivary hypersecretion      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     0/255 (0.00%)  
Toothache      
# participants affected / at risk     3/228 (1.32%)     2/114 (1.75%)     5/255 (1.96%)  
Duodenogastric reflux      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     2/255 (0.78%)  
Gastrointestinal haemorrhage      
# participants affected / at risk     2/228 (0.88%)     5/114 (4.39%)     5/255 (1.96%)  
Gingival bleeding      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     1/255 (0.39%)  
Glossitis      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     6/255 (2.35%)  
Haematochezia      
# participants affected / at risk     2/228 (0.88%)     2/114 (1.75%)     4/255 (1.57%)  
Intestinal obstruction      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     2/255 (0.78%)  
Lip pain      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     1/255 (0.39%)  
Lip ulceration      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     0/255 (0.00%)  
Melaena      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     4/255 (1.57%)  
Painful defaecation      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     2/255 (0.78%)  
Paraesthesia oral      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     1/255 (0.39%)  
Small intestinal obstruction      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     3/255 (1.18%)  
Stomach discomfort      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     4/255 (1.57%)  
Tongue blistering      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     0/255 (0.00%)  
Aerophagia      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Anal fissure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Anal fistula      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Anal inflammation      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Anorectal discomfort      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     4/255 (1.57%)  
Aphthous stomatitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Breath odour      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Chapped lips      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cheilosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Colitis ulcerative      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Epigastric discomfort      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Faecal incontinence      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Gastric haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gastric ulcer      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gastritis haemorrhagic      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gastrointestinal obstruction      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Gastrointestinal pain      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Gingival swelling      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Haematemesis      
# participants affected / at risk     1/228 (0.44%)     2/114 (1.75%)     6/255 (2.35%)  
Haemorrhoidal haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Inguinal hernia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Intestinal haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Lip swelling      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Loose tooth      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Mouth haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Odynophagia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Oesophageal haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Oesophageal pain      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Oesophageal ulcer      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Periodontal disease      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Periodontitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Proctitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Rectal lesion      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Steatorrhoea      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Tooth discolouration      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Enterovesical fistula      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Faeces discoloured      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Ileus      
# participants affected / at risk     0/228 (0.00%)     2/114 (1.75%)     2/255 (0.78%)  
Pancreatitis acute      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Subileus      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Varices oesophageal      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Abdominal tenderness      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Hiatus hernia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Anal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Gingivitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Peritoneal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Rectal tenesmus      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Upper gastrointestinal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Abdominal hernia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Abdominal mass      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Abdominal rigidity      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Defaecation urgency      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Dental caries      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Diverticulum      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Duodenal fistula      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Duodenal ulcer      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Enamel anomaly      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Enterocutaneous fistula      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Gastrointestinal disorder      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Gastrointestinal motility disorder      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Gastrointestinal sounds abnormal      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hyperchlorhydria      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hypoaesthesia oral      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Intra-abdominal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Large intestinal haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Salivary gland enlargement      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Sensitivity of teeth      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Swollen tongue      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Tongue disorder      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Tongue haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Tongue spasm      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Tongue ulceration      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Tooth erosion      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Umbilical hernia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Cheilitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Colitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
General disorders        
Fatigue      
# participants affected / at risk     104/228 (45.61%)     40/114 (35.09%)     156/255 (61.18%)  
Asthenia      
# participants affected / at risk     51/228 (22.37%)     11/114 (9.65%)     62/255 (24.31%)  
Mucosal inflammation      
# participants affected / at risk     39/228 (17.11%)     0/114 (0.00%)     49/255 (19.22%)  
Pyrexia      
# participants affected / at risk     39/228 (17.11%)     11/114 (9.65%)     52/255 (20.39%)  
Oedema peripheral      
# participants affected / at risk     30/228 (13.16%)     15/114 (13.16%)     73/255 (28.63%)  
Oedema      
# participants affected / at risk     17/228 (7.46%)     0/114 (0.00%)     14/255 (5.49%)  
Chest pain      
# participants affected / at risk     10/228 (4.39%)     5/114 (4.39%)     17/255 (6.67%)  
Chills      
# participants affected / at risk     8/228 (3.51%)     2/114 (1.75%)     9/255 (3.53%)  
Disease progression      
# participants affected / at risk     8/228 (3.51%)     4/114 (3.51%)     33/255 (12.94%)  
Pain      
# participants affected / at risk     8/228 (3.51%)     2/114 (1.75%)     13/255 (5.10%)  
Face oedema      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     9/255 (3.53%)  
Localised oedema      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     4/255 (1.57%)  
Early satiety      
# participants affected / at risk     2/228 (0.88%)     3/114 (2.63%)     9/255 (3.53%)  
Influenza like illness      
# participants affected / at risk     2/228 (0.88%)     2/114 (1.75%)     5/255 (1.96%)  
Malaise      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     6/255 (2.35%)  
Chest discomfort      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Discomfort      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Drug interaction      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Facial pain      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Gait disturbance      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
General physical health deterioration      
# participants affected / at risk     1/228 (0.44%)     3/114 (2.63%)     5/255 (1.96%)  
Infusion site reaction      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Multi-organ failure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Performance status decreased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Feeling hot      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Ill-defined disorder      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Impaired healing      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Catheter related complication      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Catheter site discharge      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Catheter site excoriation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Catheter site pain      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Cyst      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Effusion      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Feeling cold      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hernia pain      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Infusion site extravasation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Irritability      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Mucosal dryness      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Necrosis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Peripheral coldness      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Pneumatosis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Thirst      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Ulcer haemorrhage      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Xerosis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hepatobiliary disorders        
Hepatic pain      
# participants affected / at risk     3/228 (1.32%)     1/114 (0.88%)     6/255 (2.35%)  
Hyperbilirubinaemia      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     4/255 (1.57%)  
Jaundice      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     3/255 (1.18%)  
Hepatomegaly      
# participants affected / at risk     2/228 (0.88%)     2/114 (1.75%)     2/255 (0.78%)  
Acute hepatic failure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Bile duct stone      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cholangitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cholecystitis acute      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Cholelithiasis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Cholestasis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Hepatic failure      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Hepatic function abnormal      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Hepatic haemorrhage      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Portal hypertension      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Hepatotoxicity      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Portal vein thrombosis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Cholecystitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Foetor hepaticus      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Immune system disorders        
Hypersensitivity      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Seasonal allergy      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Infections and infestations        
Urinary tract infection      
# participants affected / at risk     10/228 (4.39%)     3/114 (2.63%)     22/255 (8.63%)  
Influenza      
# participants affected / at risk     8/228 (3.51%)     2/114 (1.75%)     13/255 (5.10%)  
Upper respiratory tract infection      
# participants affected / at risk     6/228 (2.63%)     1/114 (0.88%)     18/255 (7.06%)  
Cystitis      
# participants affected / at risk     5/228 (2.19%)     2/114 (1.75%)     3/255 (1.18%)  
Infection      
# participants affected / at risk     4/228 (1.75%)     0/114 (0.00%)     6/255 (2.35%)  
Nasopharyngitis      
# participants affected / at risk     4/228 (1.75%)     3/114 (2.63%)     11/255 (4.31%)  
Oral herpes      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     4/255 (1.57%)  
Sinusitis      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     8/255 (3.14%)  
Bronchitis      
# participants affected / at risk     3/228 (1.32%)     1/114 (0.88%)     2/255 (0.78%)  
Tooth abscess      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     1/255 (0.39%)  
Tooth infection      
# participants affected / at risk     3/228 (1.32%)     1/114 (0.88%)     4/255 (1.57%)  
Central line infection      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     0/255 (0.00%)  
Folliculitis      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     5/255 (1.96%)  
Gastroenteritis      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     11/255 (4.31%)  
Nail infection      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     1/255 (0.39%)  
Abscess limb      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Bacteraemia      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     2/255 (0.78%)  
Catheter sepsis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Furuncle      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Gastroenteritis viral      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Gingival abscess      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Gingival infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Herpes zoster      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     5/255 (1.96%)  
Lobar pneumonia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Localised infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Lower respiratory tract infection      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     6/255 (2.35%)  
Mediastinitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Nipple infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Oral candidiasis      
# participants affected / at risk     1/228 (0.44%)     3/114 (2.63%)     3/255 (1.18%)  
Oral fungal infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Oral infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Pilonidal cyst      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Pneumonia      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     5/255 (1.96%)  
Sinusitis bacterial      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Skin infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Staphylococcal infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Staphylococcal sepsis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Subcutaneous abscess      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Tinea infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Tinea pedis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Tonsillitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Viral infection      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     0/255 (0.00%)  
Viral oesophagitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Wound infection      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Arthritis infective      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Laryngitis      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     2/255 (0.78%)  
Postoperative wound infection      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     2/255 (0.78%)  
Respiratory tract infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     5/255 (1.96%)  
Rhinitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     6/255 (2.35%)  
Cellulitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Ear infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Pharyngitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Sepsis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Abdominal abscess      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Anal infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Bacterial infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Campylobacter infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Diverticulitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Empyema      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Fungal infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Gastrointestinal infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Genital herpes      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Herpes simplex      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Infected skin ulcer      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Liver abscess      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Lung infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Necrotising ulcerative gingivostomatitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Oesophageal candidiasis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Orchitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Osteomyelitis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Otitis media      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Perirectal abscess      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Proctitis monilial      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Pyelonephritis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Urinary tract infection fungal      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Urosepsis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Viral upper respiratory tract infection      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Injury, poisoning and procedural complications        
Contusion      
# participants affected / at risk     9/228 (3.95%)     1/114 (0.88%)     9/255 (3.53%)  
Procedural pain      
# participants affected / at risk     3/228 (1.32%)     1/114 (0.88%)     2/255 (0.78%)  
Back injury      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     2/255 (0.78%)  
Excoriation      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Medical device pain      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Periorbital haematoma      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Procedural site reaction      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Radiation oesophagitis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Spinal compression fracture      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Spinal fracture      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Sunburn      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Wound dehiscence      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Fall      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     3/255 (1.18%)  
Hepatic haematoma      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Injury      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Overdose      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Skin laceration      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     4/255 (1.57%)  
Thermal burn      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Wound      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Anal injury      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Device malfunction      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Feeding tube complication      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Joint sprain      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Ligament rupture      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Limb injury      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Medical device complication      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Medical device site reaction      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Medication error      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Muscle strain      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Neck injury      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Post gastric surgery syndrome      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Post procedural diarrhoea      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Postoperative constipation      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Postoperative fever      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Skeletal injury      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Investigations        
Weight decreased      
# participants affected / at risk     14/228 (6.14%)     6/114 (5.26%)     45/255 (17.65%)  
Platelet count decreased      
# participants affected / at risk     9/228 (3.95%)     0/114 (0.00%)     13/255 (5.10%)  
Blood creatinine increased      
# participants affected / at risk     7/228 (3.07%)     1/114 (0.88%)     20/255 (7.84%)  
Haemoglobin decreased      
# participants affected / at risk     7/228 (3.07%)     1/114 (0.88%)     11/255 (4.31%)  
Lipase increased      
# participants affected / at risk     6/228 (2.63%)     3/114 (2.63%)     8/255 (3.14%)  
Blood amylase increased      
# participants affected / at risk     5/228 (2.19%)     2/114 (1.75%)     6/255 (2.35%)  
Blood bilirubin increased      
# participants affected / at risk     5/228 (2.19%)     2/114 (1.75%)     3/255 (1.18%)  
White blood cell count decreased      
# participants affected / at risk     5/228 (2.19%)     0/114 (0.00%)     12/255 (4.71%)  
Blood alkaline phosphatase increased      
# participants affected / at risk     4/228 (1.75%)     2/114 (1.75%)     10/255 (3.92%)  
Blood creatine phosphokinase increased      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     2/255 (0.78%)  
Alanine aminotransferase increased      
# participants affected / at risk     3/228 (1.32%)     3/114 (2.63%)     8/255 (3.14%)  
Aspartate aminotransferase increased      
# participants affected / at risk     3/228 (1.32%)     1/114 (0.88%)     9/255 (3.53%)  
Neutrophil count decreased      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     11/255 (4.31%)  
Urine output decreased      
# participants affected / at risk     3/228 (1.32%)     1/114 (0.88%)     1/255 (0.39%)  
Activated partial thromboplastin time prolonged      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     2/255 (0.78%)  
International normalised ratio increased      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     2/255 (0.78%)  
Prothrombin time prolonged      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     2/255 (0.78%)  
Alanine aminotransferase abnormal      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Ammonia increased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Aspartate aminotransferase abnormal      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Blood alkaline phosphatase abnormal      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Blood bicarbonate decreased      
# participants affected / at risk     1/228 (0.44%)     2/114 (1.75%)     2/255 (0.78%)  
Blood bilirubin      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Blood creatine phosphokinase      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     3/255 (1.18%)  
Blood creatinine      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Blood magnesium decreased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Blood potassium increased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Blood pressure increased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Blood thyroid stimulating hormone increased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Blood urea increased      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     3/255 (1.18%)  
Blood urine present      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Haemoglobin      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Heart rate increased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Neutrophil count      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Neutrophil count normal      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     0/255 (0.00%)  
Oxygen saturation decreased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Transaminases increased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     3/255 (1.18%)  
Blood glucose increased      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     3/255 (1.18%)  
Blood sodium increased      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Breath sounds abnormal      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Cardiac murmur      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Electrocardiogram abnormal      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Heart rate irregular      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Occult blood positive      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Pancreatic enzymes increased      
# participants affected / at risk     0/228 (0.00%)     2/114 (1.75%)     1/255 (0.39%)  
Platelet count increased      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     2/255 (0.78%)  
Weight increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     6/255 (2.35%)  
Blood lactate dehydrogenase increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     5/255 (1.96%)  
Blood potassium decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     4/255 (1.57%)  
Blood uric acid increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     4/255 (1.57%)  
Blood albumin decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     3/255 (1.18%)  
Liver function test abnormal      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Platelet count      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Bacterial culture positive      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood alkaline phosphatase      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood calcium decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood glucose decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood phosphorus decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
C-reactive protein increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
ECG signs of myocardial ischaemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Electrocardiogram ST segment depression      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Gamma-glutamyltransferase increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hepatic enzyme increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Lymph node palpable      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Lymphocyte count decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Mean cell volume increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Multiple gated acquisition scan abnormal      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Venous pressure jugular increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Vitamin B12 decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
White blood cell count      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
White blood cell count increased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Blood sodium decreased      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Metabolism and nutrition disorders        
Anorexia      
# participants affected / at risk     76/228 (33.33%)     19/114 (16.67%)     92/255 (36.08%)  
Decreased appetite      
# participants affected / at risk     10/228 (4.39%)     5/114 (4.39%)     25/255 (9.80%)  
Hypokalaemia      
# participants affected / at risk     10/228 (4.39%)     1/114 (0.88%)     13/255 (5.10%)  
Dehydration      
# participants affected / at risk     9/228 (3.95%)     0/114 (0.00%)     19/255 (7.45%)  
Hypoalbuminaemia      
# participants affected / at risk     6/228 (2.63%)     1/114 (0.88%)     11/255 (4.31%)  
Hyperglycaemia      
# participants affected / at risk     4/228 (1.75%)     0/114 (0.00%)     10/255 (3.92%)  
Hypocalcaemia      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     4/255 (1.57%)  
Hypoglycaemia      
# participants affected / at risk     4/228 (1.75%)     1/114 (0.88%)     6/255 (2.35%)  
Hyponatraemia      
# participants affected / at risk     3/228 (1.32%)     2/114 (1.75%)     4/255 (1.57%)  
Hypercholesterolaemia      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     4/255 (1.57%)  
Hyperuricaemia      
# participants affected / at risk     2/228 (0.88%)     1/114 (0.88%)     3/255 (1.18%)  
Food intolerance      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Hypercalcaemia      
# participants affected / at risk     1/228 (0.44%)     2/114 (1.75%)     2/255 (0.78%)  
Hyperkalaemia      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Hyperphosphataemia      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     1/255 (0.39%)  
Hypertriglyceridaemia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     4/255 (1.57%)  
Hypophosphataemia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     4/255 (1.57%)  
Hypoproteinaemia      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Metabolic acidosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Acidosis      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Appetite disorder      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Gout      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     2/255 (0.78%)  
Increased appetite      
# participants affected / at risk     0/228 (0.00%)     2/114 (1.75%)     1/255 (0.39%)  
Malnutrition      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Hypomagnesaemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     5/255 (1.96%)  
Cachexia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     2/255 (0.78%)  
Cow's milk intolerance      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Fluid retention      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Hypochloraemia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Iron deficiency      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Lactose intolerance      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Polydipsia      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Musculoskeletal and connective tissue disorders        
Back pain      
# participants affected / at risk     31/228 (13.60%)     14/114 (12.28%)     51/255 (20.00%)  
Pain in extremity      
# participants affected / at risk     28/228 (12.28%)     4/114 (3.51%)     46/255 (18.04%)  
Arthralgia      
# participants affected / at risk     23/228 (10.09%)     8/114 (7.02%)     51/255 (20.00%)  
Muscle spasms      
# participants affected / at risk     15/228 (6.58%)     5/114 (4.39%)     27/255 (10.59%)  
Myalgia      
# participants affected / at risk     15/228 (6.58%)     4/114 (3.51%)     25/255 (9.80%)  
Flank pain      
# participants affected / at risk     9/228 (3.95%)     0/114 (0.00%)     10/255 (3.92%)  
Musculoskeletal pain      
# participants affected / at risk     9/228 (3.95%)     5/114 (4.39%)     28/255 (10.98%)  
Muscular weakness      
# participants affected / at risk     7/228 (3.07%)     1/114 (0.88%)     11/255 (4.31%)  
Neck pain      
# participants affected / at risk     6/228 (2.63%)     2/114 (1.75%)     12/255 (4.71%)  
Bone pain      
# participants affected / at risk     5/228 (2.19%)     2/114 (1.75%)     9/255 (3.53%)  
Musculoskeletal stiffness      
# participants affected / at risk     4/228 (1.75%)     0/114 (0.00%)     3/255 (1.18%)  
Joint stiffness      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     4/255 (1.57%)  
Limb discomfort      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     4/255 (1.57%)  
Musculoskeletal chest pain      
# participants affected / at risk     2/228 (0.88%)     3/114 (2.63%)     5/255 (1.96%)  
Pain in jaw      
# participants affected / at risk     2/228 (0.88%)     0/114 (0.00%)     0/255 (0.00%)  
Exostosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Fistula      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Groin pain      
# participants affected / at risk     1/228 (0.44%)     3/114 (2.63%)     5/255 (1.96%)  
Intervertebral disc disorder      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Joint effusion      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Joint range of motion decreased      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Muscle tightness      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Muscle twitching      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Osteoporosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     2/255 (0.78%)  
Tendonitis      
# participants affected / at risk     1/228 (0.44%)     1/114 (0.88%)     2/255 (0.78%)  
Costochondritis      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Intervertebral disc protrusion      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Mobility decreased      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     0/255 (0.00%)  
Rheumatoid arthritis      
# participants affected / at risk     0/228 (0.00%)     1/114 (0.88%)     1/255 (0.39%)  
Arthritis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Joint swelling      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Muscle contracture      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Musculoskeletal discomfort      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Myopathy      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Rotator cuff syndrome      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Sensation of heaviness      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Spinal osteoarthritis      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Tendon disorder      
# participants affected / at risk     0/228 (0.00%)     0/114 (0.00%)     1/255 (0.39%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
Tumour haemorrhage      
# participants affected / at risk     3/228 (1.32%)     0/114 (0.00%)     3/255 (1.18%)  
Basal cell carcinoma      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Haemangioma      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     1/255 (0.39%)  
Haemorrhagic tumour necrosis      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Multiple myeloma      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Neoplasm      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Tumour associated fever      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)  
Tumour lysis syndrome      
# participants affected / at risk     1/228 (0.44%)     0/114 (0.00%)     0/255 (0.00%)