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Study Of Gemcitabine Plus AG-013736 Versus Gemcitabine For Advanced Pancreatic Cancer.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00471146
First received: May 7, 2007
Last updated: June 14, 2012
Last verified: June 2012
Results First Received: February 25, 2012  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Carcinoma, Pancreatic Ductal
Interventions: Drug: AG-013736
Drug: Gemcitabine
Drug: placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

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

Reporting Groups
  Description
Axitinib + Gemcitabine Axitinib (AG-013736) tablet 5 milligram (mg) orally twice daily (BID) in cycles of 4 weeks. Gemcitabine 1000 mg per square meter (mg/m^2) 30 minutes intravenous (IV) infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Placebo + Gemcitabine Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.

Participant Flow:   Overall Study
    Axitinib + Gemcitabine     Placebo + Gemcitabine  
STARTED     314     316  
Treated     305     308  
COMPLETED     142     142  
NOT COMPLETED     172     174  
Adverse Event                 32                 33  
Withdrawal by Subject                 14                 11  
Death                 11                 12  
Lost to Follow-up                 4                 2  
Protocol Violation                 2                 2  
Objective progression or relapse                 84                 87  
Global deterioration of health status                 12                 14  
Randomized but not treated                 9                 8  
Unspecified                 4                 5  



  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
Axitinib + Gemcitabine Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Placebo + Gemcitabine Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Total Total of all reporting groups

Baseline Measures
    Axitinib + Gemcitabine     Placebo + Gemcitabine     Total  
Number of Participants  
[units: participants]
  314     316     630  
Age, Customized  
[units: Participants]
     
Less than 65 years     203     179     382  
Greater than or equal to 65 years     111     137     248  
Gender  
[units: Participants]
     
Female     123     128     251  
Male     191     188     379  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Overall Survival (OS)   [ Time Frame: Baseline until death or at least 1 year after the randomization of last participant ]

2.  Secondary:   Progression Free Survival (PFS)   [ Time Frame: Baseline until disease progression or at least 1 year after the randomization of last participant ]

3.  Secondary:   Percentage of Participants With Objective Response (OR)   [ Time Frame: Baseline, every 8 weeks until tumor progression or death ]

4.  Secondary:   Duration of Response (DR)   [ Time Frame: Baseline until death or at least 1 year after the randomization of last participant ]

5.  Secondary:   Change From Baseline in European Organization for Research and Treatment of Cancer, Quality of Life Questionnaire Core-30 (EORTC QLQ- C30) Score   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

6.  Secondary:   Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Pancreatic 26 (EORTC QLQ- PAN26) Score   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

7.  Secondary:   Change From Baseline Brief Pain Inventory-short Form (BPI-sf) Score   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

8.  Secondary:   Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) Health State Profile   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

9.  Secondary:   Change From Baseline in Euro QoL Questionnaire- 5 Dimension (EQ-5D) VAS Score   [ Time Frame: Baseline, Day 1 (D1) of each cycle (C2-C13) up to 28 days after the last dose (follow-up) or early withdrawal ]

10.  Secondary:   Population Pharmacokinetic (PK) Analysis for Axitinib (AG-013736)   [ Time Frame: Day 1 (pre-dose), Day 29, Day 57 and then every 8 weeks up to 23 months ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events
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Time Frame No text entered.
Additional Description Same event may appear as both AE and SAE, both distinctly presented. An event may be categorized as SAE in 1 subject, AE in another or one subject may have experienced both serious and nonserious event. A participant randomized for Axitinib+Gemcitabine, received Gemcitabine only and was shifted to Placebo+Gemcitabine group for safety evaluation.

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

Reporting Groups
  Description
Axitinib + Gemcitabine Axitinib (AG-013736) tablet 5 mg orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 30 minutes IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.
Placebo + Gemcitabine Placebo matched to axitinib 5 mg tablet orally BID in cycles of 4 weeks. Gemcitabine 1000 mg/m^2 IV infusion on Day 1, 8 and 15 of each cycle, in cycles of 4 weeks.

Other Adverse Events
    Axitinib + Gemcitabine     Placebo + Gemcitabine  
Total, other (not including serious) adverse events      
# participants affected / at risk     276/304     276/309  
Blood and lymphatic system disorders      
Anaemia * 1    
# participants affected / at risk     25/304 (8.22%)     51/309 (16.50%)  
Disseminated intravascular coagulation * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Eosinopenia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Erythroblastosis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Erythropenia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Granulocytopenia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Haemoglobinaemia * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Iron deficiency anaemia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Leukocytosis * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Leukopenia * 1    
# participants affected / at risk     23/304 (7.57%)     13/309 (4.21%)  
Lymphadenopathy * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Lymphocytosis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Lymphopenia * 1    
# participants affected / at risk     1/304 (0.33%)     7/309 (2.27%)  
Neutropenia * 1    
# participants affected / at risk     73/304 (24.01%)     53/309 (17.15%)  
Neutrophilia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Thrombocytopenia * 1    
# participants affected / at risk     48/304 (15.79%)     34/309 (11.00%)  
Thrombocytosis * 1    
# participants affected / at risk     4/304 (1.32%)     3/309 (0.97%)  
Cardiac disorders      
Atrial fibrillation * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Atrial flutter * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Bradycardia * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Bundle branch block right * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Cardiovascular disorder * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Cyanosis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Diastolic dysfunction * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Mitral valve incompetence * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Nodal rhythm * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Palpitations * 1    
# participants affected / at risk     4/304 (1.32%)     2/309 (0.65%)  
Pericardial effusion * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Splinter haemorrhages * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Supraventricular extrasystoles * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Tachycardia * 1    
# participants affected / at risk     1/304 (0.33%)     5/309 (1.62%)  
Ventricular tachycardia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Congenital, familial and genetic disorders      
Congenital foot malformation * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Ear and labyrinth disorders      
Auricular perichondritis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Cerumen impaction * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Deafness * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Ear discomfort * 1    
# participants affected / at risk     5/304 (1.64%)     1/309 (0.32%)  
Ear pain * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Hypoacusis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Tinnitus * 1    
# participants affected / at risk     5/304 (1.64%)     0/309 (0.00%)  
Vertigo * 1    
# participants affected / at risk     4/304 (1.32%)     5/309 (1.62%)  
Endocrine disorders      
Hyperthyroidism * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Hypoparathyroidism * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Hypothyroidism * 1    
# participants affected / at risk     15/304 (4.93%)     4/309 (1.29%)  
Thyroiditis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Eye disorders      
Asthenopia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Conjunctivitis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Diplopia * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Dry eye * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Eye pruritus * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Eyelid oedema * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Lacrimation increased * 1    
# participants affected / at risk     2/304 (0.66%)     2/309 (0.65%)  
Ocular discomfort * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Ocular hyperaemia * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Scotoma * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Vision blurred * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Visual acuity reduced * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Gastrointestinal disorders      
Abdominal discomfort * 1    
# participants affected / at risk     3/304 (0.99%)     5/309 (1.62%)  
Abdominal distension * 1    
# participants affected / at risk     12/304 (3.95%)     12/309 (3.88%)  
Abdominal hernia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Abdominal mass * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Abdominal pain * 1    
# participants affected / at risk     54/304 (17.76%)     52/309 (16.83%)  
Abdominal pain lower * 1    
# participants affected / at risk     2/304 (0.66%)     5/309 (1.62%)  
Abdominal pain upper * 1    
# participants affected / at risk     24/304 (7.89%)     24/309 (7.77%)  
Abdominal tenderness * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Anal haemorrhage * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Aphthous stomatitis * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Ascites * 1    
# participants affected / at risk     5/304 (1.64%)     9/309 (2.91%)  
Cheilitis * 1    
# participants affected / at risk     4/304 (1.32%)     1/309 (0.32%)  
Colitis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Constipation * 1    
# participants affected / at risk     88/304 (28.95%)     91/309 (29.45%)  
Dental caries * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Diarrhoea * 1    
# participants affected / at risk     96/304 (31.58%)     64/309 (20.71%)  
Dry mouth * 1    
# participants affected / at risk     14/304 (4.61%)     14/309 (4.53%)  
Duodenal obstruction * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Duodenal ulcer * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Duodenogastric reflux * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Dyspepsia * 1    
# participants affected / at risk     14/304 (4.61%)     22/309 (7.12%)  
Dysphagia * 1    
# participants affected / at risk     7/304 (2.30%)     1/309 (0.32%)  
Enteritis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Eructation * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Faeces discoloured * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Faeces pale * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Flatulence * 1    
# participants affected / at risk     8/304 (2.63%)     9/309 (2.91%)  
Frequent bowel movements * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Gastritis * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Gastritis erosive * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Gastrointestinal disorder * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Gastrointestinal obstruction * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Gastrooesophageal reflux disease * 1    
# participants affected / at risk     6/304 (1.97%)     4/309 (1.29%)  
Gingival bleeding * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Gingival pain * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Gingival ulceration * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Gingivitis * 1    
# participants affected / at risk     6/304 (1.97%)     1/309 (0.32%)  
Glossitis * 1    
# participants affected / at risk     7/304 (2.30%)     0/309 (0.00%)  
Glossodynia * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Haematemesis * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Haematochezia * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Haemorrhoids * 1    
# participants affected / at risk     4/304 (1.32%)     5/309 (1.62%)  
Hiatus hernia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Ileus * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Intestinal obstruction * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Lip dry * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Mouth ulceration * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Nausea * 1    
# participants affected / at risk     138/304 (45.39%)     112/309 (36.25%)  
Odynophagia * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Oesophageal pain * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Oesophagitis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Oral discomfort * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Oral disorder * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Oral dysaesthesia * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Oral pain * 1    
# participants affected / at risk     4/304 (1.32%)     0/309 (0.00%)  
Pancreatic insufficiency * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pancreatitis acute * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Periodontitis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Pneumoperitoneum * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Proctalgia * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Rectal haemorrhage * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Reflux gastritis * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Reflux oesophagitis * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Regurgitation * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Retching * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Salivary hypersecretion * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Steatorrhoea * 1    
# participants affected / at risk     2/304 (0.66%)     2/309 (0.65%)  
Stomatitis * 1    
# participants affected / at risk     52/304 (17.11%)     12/309 (3.88%)  
Thrombosis mesenteric vessel * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Toothache * 1    
# participants affected / at risk     3/304 (0.99%)     2/309 (0.65%)  
Vomiting * 1    
# participants affected / at risk     91/304 (29.93%)     95/309 (30.74%)  
Mass * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
General disorders      
Adhesion * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Asthenia * 1    
# participants affected / at risk     38/304 (12.50%)     38/309 (12.30%)  
Catheter site erythema * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Catheter site haemorrhage * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Catheter site pain * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Catheter site pruritus * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Chest discomfort * 1    
# participants affected / at risk     2/304 (0.66%)     2/309 (0.65%)  
Chest pain * 1    
# participants affected / at risk     10/304 (3.29%)     6/309 (1.94%)  
Chills * 1    
# participants affected / at risk     13/304 (4.28%)     11/309 (3.56%)  
Device occlusion * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Early satiety * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Face oedema * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Fatigue * 1    
# participants affected / at risk     125/304 (41.12%)     113/309 (36.57%)  
Feeling cold * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Feeling hot * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
General physical health deterioration * 1    
# participants affected / at risk     6/304 (1.97%)     2/309 (0.65%)  
Generalised oedema * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hernia pain * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hyperthermia * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Influenza like illness * 1    
# participants affected / at risk     9/304 (2.96%)     9/309 (2.91%)  
Injection site extravasation * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Injection site reaction * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Malaise * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Mucosal dryness * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Mucosal inflammation * 1    
# participants affected / at risk     34/304 (11.18%)     13/309 (4.21%)  
Oedema * 1    
# participants affected / at risk     6/304 (1.97%)     5/309 (1.62%)  
Oedema peripheral * 1    
# participants affected / at risk     22/304 (7.24%)     46/309 (14.89%)  
Pain * 1    
# participants affected / at risk     16/304 (5.26%)     7/309 (2.27%)  
Performance status decreased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Pyrexia * 1    
# participants affected / at risk     38/304 (12.50%)     44/309 (14.24%)  
Thirst * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Thrombosis in device * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Ulcer * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hepatobiliary disorders      
Bile duct obstruction * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Cholangitis * 1    
# participants affected / at risk     4/304 (1.32%)     4/309 (1.29%)  
Cholestasis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Cytolytic hepatitis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hepatic function abnormal * 1    
# participants affected / at risk     4/304 (1.32%)     2/309 (0.65%)  
Hepatic pain * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Hepatomegaly * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Hepatorenal syndrome * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hepatotoxicity * 1    
# participants affected / at risk     6/304 (1.97%)     1/309 (0.32%)  
Hyperbilirubinaemia * 1    
# participants affected / at risk     6/304 (1.97%)     9/309 (2.91%)  
Jaundice * 1    
# participants affected / at risk     3/304 (0.99%)     1/309 (0.32%)  
Liver disorder * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Liver tenderness * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Portal vein thrombosis * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Immune system disorders      
Contrast media allergy * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Food allergy * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Hypersensitivity * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Seasonal allergy * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Infections and infestations      
Abscess * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Acariasis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Arthritis infective * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Bacterial infection * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Biliary tract infection * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Bronchitis * 1    
# participants affected / at risk     3/304 (0.99%)     1/309 (0.32%)  
Candidiasis * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Catheter site infection * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Cellulitis * 1    
# participants affected / at risk     3/304 (0.99%)     4/309 (1.29%)  
Cystitis * 1    
# participants affected / at risk     4/304 (1.32%)     3/309 (0.97%)  
Device related infection * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Enteritis infectious * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Erysipelas * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Escherichia infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Eye infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Fungal infection * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Furuncle * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Gastroenteritis * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Infection * 1    
# participants affected / at risk     4/304 (1.32%)     1/309 (0.32%)  
Influenza * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Localised infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Lower respiratory tract infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Lung infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Lymphangitis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Nasopharyngitis * 1    
# participants affected / at risk     9/304 (2.96%)     7/309 (2.27%)  
Oesophageal candidiasis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Oral candidiasis * 1    
# participants affected / at risk     6/304 (1.97%)     5/309 (1.62%)  
Oral fungal infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Oral herpes * 1    
# participants affected / at risk     3/304 (0.99%)     1/309 (0.32%)  
Oral infection * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Oropharyngeal candidiasis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Perichondritis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pharyngitis * 1    
# participants affected / at risk     6/304 (1.97%)     0/309 (0.00%)  
Pharyngotonsillitis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pneumonia * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Pseudomonas infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Respiratory tract infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Rhinitis * 1    
# participants affected / at risk     1/304 (0.33%)     3/309 (0.97%)  
Sepsis * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Septic encephalopathy * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Septic shock * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Sinusitis * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Skin candida * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Tooth abscess * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Tooth infection * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Upper respiratory tract infection * 1    
# participants affected / at risk     8/304 (2.63%)     2/309 (0.65%)  
Urinary tract infection * 1    
# participants affected / at risk     9/304 (2.96%)     11/309 (3.56%)  
Viral infection * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Injury, poisoning and procedural complications      
Anal injury * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Arthropod bite * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Burn oesophageal * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Contusion * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Drug toxicity * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Eschar * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Fall * 1    
# participants affected / at risk     2/304 (0.66%)     2/309 (0.65%)  
Feeding tube complication * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Humerus fracture * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Incision site pain * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Incisional hernia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Medication error * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Overdose * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Post procedural complication * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Post procedural haematoma * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Post procedural haemorrhage * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Postoperative wound complication * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Procedural pain * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Skin laceration * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Spinal compression fracture * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Wound * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Wound dehiscence * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Investigations      
Activated partial thromboplastin time prolonged * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Alanine aminotransferase * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Alanine aminotransferase increased * 1    
# participants affected / at risk     29/304 (9.54%)     24/309 (7.77%)  
Ammonia increased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Aspartate aminotransferase * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Aspartate aminotransferase increased * 1    
# participants affected / at risk     24/304 (7.89%)     21/309 (6.80%)  
Bacterial test positive * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Blood albumin decreased * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Blood alkaline phosphatase * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Blood alkaline phosphatase increased * 1    
# participants affected / at risk     15/304 (4.93%)     11/309 (3.56%)  
Blood amylase increased * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Blood bilirubin * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Blood bilirubin increased * 1    
# participants affected / at risk     6/304 (1.97%)     9/309 (2.91%)  
Blood creatinine increased * 1    
# participants affected / at risk     1/304 (0.33%)     5/309 (1.62%)  
Blood culture positive * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Blood fibrinogen increased * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Blood glucose decreased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Blood glucose increased * 1    
# participants affected / at risk     3/304 (0.99%)     6/309 (1.94%)  
Blood lactate dehydrogenase increased * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Blood magnesium decreased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Blood potassium decreased * 1    
# participants affected / at risk     0/304 (0.00%)     3/309 (0.97%)  
Blood potassium increased * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Blood pressure increased * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Blood sodium decreased * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Blood thyroid stimulating hormone decreased * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Blood thyroid stimulating hormone increased * 1    
# participants affected / at risk     16/304 (5.26%)     0/309 (0.00%)  
Blood urea increased * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Blood urine * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Blood urine present * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Body temperature increased * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
C-reactive protein increased * 1    
# participants affected / at risk     3/304 (0.99%)     3/309 (0.97%)  
Eastern cooperative oncology group performance status worsened * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Electrocardiogram QRS complex abnormal * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Electrocardiogram QT prolonged * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Fibrin D dimer increased * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Gamma-glutamyltransferase increased * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Haematocrit decreased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Haemoglobin * 1    
# participants affected / at risk     0/304 (0.00%)     3/309 (0.97%)  
Haemoglobin decreased * 1    
# participants affected / at risk     18/304 (5.92%)     26/309 (8.41%)  
International normalised ratio increased * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Liver function test abnormal * 1    
# participants affected / at risk     4/304 (1.32%)     1/309 (0.32%)  
Lymph node palpable * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Lymphocyte count decreased * 1    
# participants affected / at risk     6/304 (1.97%)     4/309 (1.29%)  
Mean cell volume abnormal * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Monocyte count decreased * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Monocyte count increased * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Monocyte percentage increased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Neutrophil count * 1    
# participants affected / at risk     5/304 (1.64%)     0/309 (0.00%)  
Neutrophil count decreased * 1    
# participants affected / at risk     31/304 (10.20%)     38/309 (12.30%)  
Neutrophil percentage decreased * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Oxygen saturation decreased * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Platelet count * 1    
# participants affected / at risk     4/304 (1.32%)     1/309 (0.32%)  
Platelet count decreased * 1    
# participants affected / at risk     43/304 (14.14%)     40/309 (12.94%)  
Platelet count increased * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Protein total decreased * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Protein urine * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Protein urine present * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Prothrombin time abnormal * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Prothrombin time prolonged * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Prothrombin time shortened * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Red blood cell count decreased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Red cell distribution width increased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Thyroxine free increased * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Transaminases increased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Tri-iodothyronine free decreased * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Tri-iodothyronine free increased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Urine output decreased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Weight decreased * 1    
# participants affected / at risk     44/304 (14.47%)     29/309 (9.39%)  
Weight increased * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
White blood cell count * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
White blood cell count decreased * 1    
# participants affected / at risk     20/304 (6.58%)     16/309 (5.18%)  
Metabolism and nutrition disorders      
Decreased appetite * 1    
# participants affected / at risk     115/304 (37.83%)     87/309 (28.16%)  
Dehydration * 1    
# participants affected / at risk     5/304 (1.64%)     12/309 (3.88%)  
Diabetes mellitus * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Fluid overload * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Gout * 1    
# participants affected / at risk     3/304 (0.99%)     1/309 (0.32%)  
Hyperammonaemia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Hypercalcaemia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hyperglycaemia * 1    
# participants affected / at risk     9/304 (2.96%)     5/309 (1.62%)  
Hyperkalaemia * 1    
# participants affected / at risk     0/304 (0.00%)     3/309 (0.97%)  
Hyperlipasaemia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Hypernatraemia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hyperuricaemia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hypoalbuminaemia * 1    
# participants affected / at risk     4/304 (1.32%)     5/309 (1.62%)  
Hypocalcaemia * 1    
# participants affected / at risk     1/304 (0.33%)     4/309 (1.29%)  
Hypoglycaemia * 1    
# participants affected / at risk     2/304 (0.66%)     3/309 (0.97%)  
Hypokalaemia * 1    
# participants affected / at risk     13/304 (4.28%)     8/309 (2.59%)  
Hypomagnesaemia * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Hyponatraemia * 1    
# participants affected / at risk     4/304 (1.32%)     6/309 (1.94%)  
Hypophosphataemia * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Hypoproteinaemia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Lactic acidosis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Malnutrition * 1    
# participants affected / at risk     2/304 (0.66%)     2/309 (0.65%)  
Metabolic acidosis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Musculoskeletal and connective tissue disorders      
Arthralgia * 1    
# participants affected / at risk     10/304 (3.29%)     11/309 (3.56%)  
Back pain * 1    
# participants affected / at risk     34/304 (11.18%)     30/309 (9.71%)  
Bone pain * 1    
# participants affected / at risk     3/304 (0.99%)     2/309 (0.65%)  
Bone swelling * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Flank pain * 1    
# participants affected / at risk     2/304 (0.66%)     5/309 (1.62%)  
Gouty arthritis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Intervertebral disc degeneration * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Joint swelling * 1    
# participants affected / at risk     0/304 (0.00%)     4/309 (1.29%)  
Muscle contracture * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Muscle spasms * 1    
# participants affected / at risk     7/304 (2.30%)     3/309 (0.97%)  
Muscle twitching * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Muscular weakness * 1    
# participants affected / at risk     4/304 (1.32%)     3/309 (0.97%)  
Musculoskeletal chest pain * 1    
# participants affected / at risk     2/304 (0.66%)     7/309 (2.27%)  
Musculoskeletal discomfort * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Musculoskeletal pain * 1    
# participants affected / at risk     13/304 (4.28%)     7/309 (2.27%)  
Musculoskeletal stiffness * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Myalgia * 1    
# participants affected / at risk     11/304 (3.62%)     14/309 (4.53%)  
Neck pain * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Osteoarthritis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Pain in extremity * 1    
# participants affected / at risk     8/304 (2.63%)     11/309 (3.56%)  
Pain in jaw * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Synovial cyst * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Torticollis * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Trigger finger * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Upper extremity mass * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Cancer pain * 1    
# participants affected / at risk     8/304 (2.63%)     4/309 (1.29%)  
Tumour associated fever * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Tumour pain * 1    
# participants affected / at risk     2/304 (0.66%)     2/309 (0.65%)  
Nervous system disorders      
Ageusia * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Amnesia * 1    
# participants affected / at risk     3/304 (0.99%)     2/309 (0.65%)  
Anaesthesia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Aphasia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Aphonia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Cognitive disorder * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Cranial nerve disorder * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Dizziness * 1    
# participants affected / at risk     10/304 (3.29%)     17/309 (5.50%)  
Dysaesthesia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Dysarthria * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Dysgeusia * 1    
# participants affected / at risk     25/304 (8.22%)     14/309 (4.53%)  
Extrapyramidal disorder * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Headache * 1    
# participants affected / at risk     45/304 (14.80%)     26/309 (8.41%)  
Hyperaesthesia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hypersomnia * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Hypoaesthesia * 1    
# participants affected / at risk     6/304 (1.97%)     2/309 (0.65%)  
Lethargy * 1    
# participants affected / at risk     8/304 (2.63%)     12/309 (3.88%)  
Loss of consciousness * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Memory impairment * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Metabolic encephalopathy * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Migraine * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Myoclonus * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Neuropathy peripheral * 1    
# participants affected / at risk     3/304 (0.99%)     1/309 (0.32%)  
Paraesthesia * 1    
# participants affected / at risk     4/304 (1.32%)     4/309 (1.29%)  
Peripheral sensory neuropathy * 1    
# participants affected / at risk     3/304 (0.99%)     7/309 (2.27%)  
Polyneuropathy * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Poor quality sleep * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Sciatica * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Sinus headache * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Somnolence * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Syncope * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Tremor * 1    
# participants affected / at risk     3/304 (0.99%)     1/309 (0.32%)  
Psychiatric disorders      
Agitation * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Anxiety * 1    
# participants affected / at risk     16/304 (5.26%)     19/309 (6.15%)  
Aversion * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Confusional state * 1    
# participants affected / at risk     7/304 (2.30%)     3/309 (0.97%)  
Decreased activity * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Delirium * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Depression * 1    
# participants affected / at risk     14/304 (4.61%)     10/309 (3.24%)  
Dysphoria * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Hallucination * 1    
# participants affected / at risk     2/304 (0.66%)     3/309 (0.97%)  
Hallucinations, mixed * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Insomnia * 1    
# participants affected / at risk     25/304 (8.22%)     18/309 (5.83%)  
Loss of libido * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Nightmare * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Paranoia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Sleep disorder * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Vomiting psychogenic * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Renal and urinary disorders      
Bladder pain * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Chromaturia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Dysuria * 1    
# participants affected / at risk     5/304 (1.64%)     1/309 (0.32%)  
Haematuria * 1    
# participants affected / at risk     4/304 (1.32%)     4/309 (1.29%)  
Hydronephrosis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Micturition urgency * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pollakiuria * 1    
# participants affected / at risk     4/304 (1.32%)     3/309 (0.97%)  
Polyuria * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Proteinuria * 1    
# participants affected / at risk     17/304 (5.59%)     12/309 (3.88%)  
Pyuria * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Renal failure acute * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Renal impairment * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Urethral pain * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Urinary incontinence * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Reproductive system and breast disorders      
Breast enlargement * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Genital haemorrhage * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Menopausal symptoms * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Metrorrhagia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Prostatism * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pruritus genital * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Scrotal ulcer * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Vaginal haemorrhage * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Vulvovaginal dryness * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Vulvovaginal pruritus * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Respiratory, thoracic and mediastinal disorders      
Asphyxia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Asthma * 1    
# participants affected / at risk     0/304 (0.00%)     2/309 (0.65%)  
Atelectasis * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Cough * 1    
# participants affected / at risk     24/304 (7.89%)     19/309 (6.15%)  
Dry throat * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Dysphonia * 1    
# participants affected / at risk     68/304 (22.37%)     12/309 (3.88%)  
Dyspnoea * 1    
# participants affected / at risk     24/304 (7.89%)     20/309 (6.47%)  
Dyspnoea exertional * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Epistaxis * 1    
# participants affected / at risk     14/304 (4.61%)     7/309 (2.27%)  
Haemoptysis * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Hiccups * 1    
# participants affected / at risk     6/304 (1.97%)     3/309 (0.97%)  
Hypoxia * 1    
# participants affected / at risk     1/304 (0.33%)     3/309 (0.97%)  
Interstitial lung disease * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Laryngeal oedema * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Nasal congestion * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Nasal dryness * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Nasal mucosal disorder * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Nasal ulcer * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Oropharyngeal discomfort * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Oropharyngeal pain * 1    
# participants affected / at risk     12/304 (3.95%)     1/309 (0.32%)  
Painful respiration * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pharyngeal oedema * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pleural effusion * 1    
# participants affected / at risk     0/304 (0.00%)     6/309 (1.94%)  
Pneumothorax * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Productive cough * 1    
# participants affected / at risk     3/304 (0.99%)     2/309 (0.65%)  
Pulmonary congestion * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pulmonary embolism * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Pulmonary hypertension * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Pulmonary oedema * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Rales * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Rhinalgia * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Rhinitis allergic * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Rhinorrhoea * 1    
# participants affected / at risk     4/304 (1.32%)     2/309 (0.65%)  
Sinus congestion * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Sputum increased * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Upper-airway cough syndrome * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Wheezing * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Skin and subcutaneous tissue disorders      
Acne * 1    
# participants affected / at risk     4/304 (1.32%)     1/309 (0.32%)  
Alopecia * 1    
# participants affected / at risk     31/304 (10.20%)     20/309 (6.47%)  
Circumoral oedema * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Cold sweat * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Decubitus ulcer * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Dermatitis * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Dermatitis acneiform * 1    
# participants affected / at risk     4/304 (1.32%)     0/309 (0.00%)  
Dermatitis allergic * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Dermatitis contact * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Dry skin * 1    
# participants affected / at risk     7/304 (2.30%)     2/309 (0.65%)  
Eczema * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Erythema * 1    
# participants affected / at risk     3/304 (0.99%)     5/309 (1.62%)  
Hair texture abnormal * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Heat rash * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Hyperhidrosis * 1    
# participants affected / at risk     3/304 (0.99%)     3/309 (0.97%)  
Increased tendency to bruise * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Nail bed bleeding * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Nail bed inflammation * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Nail disorder * 1    
# participants affected / at risk     5/304 (1.64%)     1/309 (0.32%)  
Night sweats * 1    
# participants affected / at risk     3/304 (0.99%)     9/309 (2.91%)  
Pain of skin * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Palmar-plantar erythrodysaesthesia syndrome * 1    
# participants affected / at risk     18/304 (5.92%)     2/309 (0.65%)  
Petechiae * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Pigmentation disorder * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Pruritus * 1    
# participants affected / at risk     14/304 (4.61%)     17/309 (5.50%)  
Pruritus generalised * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Rash * 1    
# participants affected / at risk     43/304 (14.14%)     41/309 (13.27%)  
Rash erythematous * 1    
# participants affected / at risk     3/304 (0.99%)     0/309 (0.00%)  
Rash generalised * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Rash macular * 1    
# participants affected / at risk     1/304 (0.33%)     3/309 (0.97%)  
Rash papular * 1    
# participants affected / at risk     2/304 (0.66%)     1/309 (0.32%)  
Rash pruritic * 1    
# participants affected / at risk     1/304 (0.33%)     4/309 (1.29%)  
Scab * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Skin exfoliation * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Skin fissures * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Skin hyperpigmentation * 1    
# participants affected / at risk     3/304 (0.99%)     2/309 (0.65%)  
Skin induration * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Skin irritation * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Skin lesion * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Skin nodule * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Skin reaction * 1    
# participants affected / at risk     10/304 (3.29%)     1/309 (0.32%)  
Skin toxicity * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Subcutaneous nodule * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Swelling face * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Urticaria * 1    
# participants affected / at risk     4/304 (1.32%)     1/309 (0.32%)  
Surgical and medical procedures      
Abdominal cavity drainage * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Vascular disorders      
Angiopathy * 1    
# participants affected / at risk     1/304 (0.33%)     2/309 (0.65%)  
Deep vein thrombosis * 1    
# participants affected / at risk     4/304 (1.32%)     9/309 (2.91%)  
Flushing * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Haemorrhage * 1    
# participants affected / at risk     1/304 (0.33%)     1/309 (0.32%)  
Hot flush * 1    
# participants affected / at risk     5/304 (1.64%)     1/309 (0.32%)  
Hypertension * 1    
# participants affected / at risk     84/304 (27.63%)     26/309 (8.41%)  
Hypotension * 1    
# participants affected / at risk     9/304 (2.96%)     14/309 (4.53%)  
Orthostatic hypotension * 1    
# participants affected / at risk     2/304 (0.66%)     0/309 (0.00%)  
Pallor * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
Phlebitis * 1    
# participants affected / at risk     2/304 (0.66%)     5/309 (1.62%)  
Phlebitis superficial * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Thrombophlebitis * 1    
# participants affected / at risk     0/304 (0.00%)     3/309 (0.97%)  
Thrombophlebitis superficial * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Thrombosis * 1    
# participants affected / at risk     2/304 (0.66%)     3/309 (0.97%)  
Vein pain * 1    
# participants affected / at risk     0/304 (0.00%)     1/309 (0.32%)  
Venous thrombosis * 1    
# participants affected / at risk     1/304 (0.33%)     0/309 (0.00%)  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA v13.1



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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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