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Randomized Study Comparing Docetaxel Plus Dasatinib to Docetaxel Plus Placebo in Castration-resistant Prostate Cancer (READY)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00744497
First received: August 29, 2008
Last updated: August 23, 2016
Last verified: August 2016
Results First Received: November 15, 2013  
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: Prostatic Neoplasms
Interventions: Drug: Placebo
Drug: Dasatinib
Drug: Docetaxel
Drug: Prednisone

  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
1930 participants enrolled, 1522 randomized to a treatment group (762 dasatinib, 760 placebo). 408 not randomized. Reasons for non-randomization include 7 adverse events, 42 withdrew consent, 6 deaths, 2 lost to follow up, 3 poor/non compliance, 332 no longer met study criteria, 1 administrative reason by sponsor, and 15 non-specified reasons.

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Participant Flow:   Overall Study
    Placebo   Dasatinib
STARTED   760 [1]   762 [1] 
Received Treatment   757   761 
COMPLETED   0   0 
NOT COMPLETED   760   762 
Withdrawal by Subject                21                18 
Death                11                9 
Lost to Follow-up                4                2 
Poor compliance/noncompliance                9                5 
No longer meets study criteria                7                3 
Administrative Reason By Sponsor                25                8 
Disease progression                312                219 
Study drug toxicity                68                141 
Adverse event unrelated to study drug                78                122 
Patient requested to stop study drug                65                80 
Maximum clinical benefit                141                142 
Not defined                19                13 
[1] Randomized



  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.
All participants who were randomized to receive any treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Total Total of all reporting groups

Baseline Measures
   Placebo   Dasatinib   Total 
Overall Participants Analyzed 
[Units: Participants]
 760   762   1522 
Age, Customized 
[Units: Participants]
     
Younger than 65 years   263   251   514 
65 to younger than 75 years   323   333   656 
75 years or older   174   178   352 
Gender 
[Units: Participants]
     
Female   0   0   0 
Male   760   762   1522 
Race/Ethnicity, Customized 
[Units: Participants]
     
Asian   56   55   111 
Native Hawaiian or Other Pacific Islander   1   1   2 
Black or African American   34   23   57 
White   645   656   1301 
Other   24   27   51 
Type of metastatic disease 
[Units: Participants]
     
Bone disease only   286   307   593 
Visceral/nodal disease only   73   80   153 
Both bone and visceral/nodal disease   399   373   772 
No evidence of metastatic disease   2   2   4 


  Outcome Measures
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1.  Primary:   Overall Survival: Time From Randomization to Date of Death   [ Time Frame: From randomization to death or date of last contact (maximum reached: 45 months) ]
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Measure Type Primary
Measure Title Overall Survival: Time From Randomization to Date of Death
Measure Description Overall survival is defined as time in months from the randomization date to the date of death due to any cause (in the randomized population). If the patient did not die, survival was censored on the last date he or she was known to be alive.
Time Frame From randomization to death or date of last contact (maximum reached: 45 months)  
Safety Issue No  

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.
All participants who were randomized to receive any treatment

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Measured Values
   Placebo   Dasatinib 
Participants Analyzed 
[Units: Participants]
 760   762 
Overall Survival: Time From Randomization to Date of Death 
[Units: Months]
Median (95% Confidence Interval)
 21.2 
 (20.0 to 23.4) 
 21.5 
 (20.3 to 22.8) 


Statistical Analysis 1 for Overall Survival: Time From Randomization to Date of Death
Groups [1] All groups
Method [2] Log Rank
P Value [3] 0.9009
Hazard Ratio (HR) [4] 0.99
95.53% Confidence Interval 0.87 to 1.13
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  Confidence intervals for median overall survival calculated using Brookmeyer and Crowley method. Compared survival in arms by 2-sided, alpha=0.0447 level, log-rank test, stratified by bisphosphonate intake (yes/no) and urinary N-telopeptide category (<60 vs ≥60 nmol/mmol creatinine) defined at randomization. Null hypothesis was survival equal in both arms. Power calculations were that ≥858 deaths would lead to ≥90% power at 5% level for rejecting null hypothesis, given true hazard ratio of 0.8.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  An interim analysis on survival was performed and the final test was corrected for multiplicity.
[4] Other relevant estimation information:
  No text entered.



2.  Secondary:   Percentage of Participants With an Objective Tumor Response by Modified Response Evaluation Criteria in Solid Tumors (RECIST)   [ Time Frame: At baseline and every 12 weeks thereafter to end of treatment, at end of treatment, and at follow-up (within 42 days of end of dosing) ]

3.  Secondary:   Time to First Skeletal-related Event (SRE)   [ Time Frame: From day of randomization to date of first SRE or to last SRE assessment, if subsequent cancer therapy begun or no SRE (maximum reached: 42 months) ]

4.  Secondary:   Percentage of Participants With A Reduction in Urinary N-telopeptide (uNTx) Level From Baseline   [ Time Frame: At baseline, prior to each docetaxel infusion (every 3 weeks) to end of treatment, at end of treatment, and at follow-up (within 14 days of end of dosing) ]

5.  Secondary:   Progression-free Survival (PFS)   [ Time Frame: From day of randomization to disease progression or death (or to last clinical assessment, if subsequent cancer therapy started or no progression or death) (maximum reached: approximately 43 months) ]

6.  Secondary:   Time to Prostate Specific Antigen (PSA) Progression   [ Time Frame: From randomization to date of first PSA measurement leading to confirmed PSA progression (or to last bone scan assessment, if no progression or if cancer therapy started) (maximum reached: 30 months) ]

7.  Secondary:   Percentage of Participants With a Reduction in Pain Intensity From Baseline   [ Time Frame: At baseline, prior to each docetaxel infusion (every 3 weeks), at end of treatment, and at follow-up (within 14 days of end of dosing) ]

8.  Other Pre-specified:   Number of Participants With Serious Adverse Event (SAEs), Drug-related SAEs, Drug-related AEs, Drug-related AEs Leading to Discontinuation, and All Deaths   [ Time Frame: Continuously throughout study to <=30 days after last dose of study drug; included AEs with an onset date >= day 1 and <= last dose date + 30 days ]

9.  Other Pre-specified:   Number of Participants With Drug-Related Adverse Events (AEs) of Special Interest   [ Time Frame: Continuously throughout study to <=30 days after last dose of study drug; included AEs with an onset date >= day 1 and <= last dose date + 30 days ]

10.  Other Pre-specified:   Number of Participants With Abnormalities in Results of Clinical Laboratory Tests in Hematology   [ Time Frame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle) and at end of treatment. If docetaxel is discontinued, every other cycle. ]

11.  Other Pre-specified:   Number of Participants With Abnormalities in Results of Clinical Laboratory Tests Assessing Liver Function, Renal Function, and Electrolytes   [ Time Frame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle. ]

12.  Other Pre-specified:   Number of Participants With Abnormal Results in Urinalysis   [ Time Frame: At baseline, within 3 days prior to each infusion of docetaxel (each cycle), to end of treatment. If docetaxel is discontinued, every other cycle. ]

13.  Other Pre-specified:   Number of Participants by Maximal On-study Fridericia-corrected QTc Interval   [ Time Frame: At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing ]

14.  Other Pre-specified:   Number of Participants With Changes From Baseline in Fridericia-corrected QTc Interval   [ Time Frame: At baseline, approximately 12 weeks after starting treatment, and then whenever clinically indicated up to within 30 days of end of dosing ]

15.  Other Pre-specified:   Number of Participants With and Without Pericardial Effusion at Baseline and On-study and With Left Ventricular Ejection Fraction (LVEF) <40% and >=40% On-study   [ Time Frame: At baseline, approximately 12 weeks after start of treatment, and thereafter whenever clinically indicated ]


  Serious Adverse Events
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Time Frame Day 1 up to 30 days post last dose of study therapy
Additional Description Study initiated: October 2008; Study Completion: July 2015

Reporting Groups
  Description
Placebo Participants received placebo, given orally once daily, plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily
Dasatinib Participants received dasatinib, 100 mg, orally once daily plus docetaxel, 75 mg/m^2, given intravenously every 3 weeks as a 1-hour infusion, plus prednisone, 5 mg, given orally twice daily

Serious Adverse Events
    Placebo   Dasatinib
Total, serious adverse events     
# participants affected / at risk   317/757 (41.88%)   381/761 (50.07%) 
Blood and lymphatic system disorders     
Febrile bone marrow aplasia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Hypochromic anaemia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Leukopenia † 1     
# participants affected / at risk   7/757 (0.92%)   9/761 (1.18%) 
Anaemia † 1     
# participants affected / at risk   15/757 (1.98%)   21/761 (2.76%) 
Agranulocytosis † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Neutropenia † 1     
# participants affected / at risk   18/757 (2.38%)   19/761 (2.50%) 
Normochromic normocytic anaemia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Disseminated intravascular coagulation † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Thrombocytopenia † 1     
# participants affected / at risk   2/757 (0.26%)   1/761 (0.13%) 
Febrile neutropenia † 1     
# participants affected / at risk   27/757 (3.57%)   32/761 (4.20%) 
Haemorrhagic anaemia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Cardiac disorders     
Supraventricular tachycardia † 1     
# participants affected / at risk   2/757 (0.26%)   1/761 (0.13%) 
Cardiopulmonary failure † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Sinus node dysfunction † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Acute coronary syndrome † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Coronary artery disease † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Atrial flutter † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Cardiac arrest † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Cardio-respiratory arrest † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Tachycardia † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Acute myocardial infarction † 1     
# participants affected / at risk   0/757 (0.00%)   3/761 (0.39%) 
Cardiac failure † 1     
# participants affected / at risk   3/757 (0.40%)   1/761 (0.13%) 
Myocardial ischaemia † 1     
# participants affected / at risk   2/757 (0.26%)   2/761 (0.26%) 
Pericardial effusion † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Atrial fibrillation † 1     
# participants affected / at risk   8/757 (1.06%)   8/761 (1.05%) 
Atrioventricular block second degree † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Left ventricular dysfunction † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Supraventricular tachyarrhythmia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Cardiac failure congestive † 1     
# participants affected / at risk   3/757 (0.40%)   1/761 (0.13%) 
Myocardial infarction † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Angina pectoris † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Arrhythmia † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Cardiac disorder † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Congenital, familial and genetic disorders     
Hydrocele † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Eye disorders     
Maculopathy † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Amaurosis fugax † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Gastrointestinal disorders     
Abdominal hernia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Dyspepsia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Enterovesical fistula † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Gastric haemorrhage † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Large intestinal obstruction † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Reflux gastritis † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Stomatitis † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Colitis † 1     
# participants affected / at risk   0/757 (0.00%)   4/761 (0.53%) 
Diverticular perforation † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Gastritis erosive † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Melaena † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Mouth ulceration † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Nausea † 1     
# participants affected / at risk   7/757 (0.92%)   13/761 (1.71%) 
Anal fissure † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Anal fistula † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Gastrooesophageal reflux disease † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Intra-abdominal haemorrhage † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Megacolon † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Periodontal disease † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Subileus † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Duodenal ulcer haemorrhage † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Gastric ulcer † 1     
# participants affected / at risk   3/757 (0.40%)   2/761 (0.26%) 
Proctalgia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Proctitis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Volvulus † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Abdominal pain † 1     
# participants affected / at risk   3/757 (0.40%)   6/761 (0.79%) 
Abdominal pain upper † 1     
# participants affected / at risk   3/757 (0.40%)   1/761 (0.13%) 
Duodenal ulcer perforation † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Haematochezia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Intestinal perforation † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Peptic ulcer † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Haematemesis † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Ileus † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Inguinal hernia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Rectal haemorrhage † 1     
# participants affected / at risk   5/757 (0.66%)   8/761 (1.05%) 
Diarrhoea † 1     
# participants affected / at risk   10/757 (1.32%)   44/761 (5.78%) 
Enteritis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Gastric ulcer perforation † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Intestinal obstruction † 1     
# participants affected / at risk   2/757 (0.26%)   1/761 (0.13%) 
Vomiting † 1     
# participants affected / at risk   10/757 (1.32%)   14/761 (1.84%) 
Constipation † 1     
# participants affected / at risk   10/757 (1.32%)   5/761 (0.66%) 
Dysphagia † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Gastrointestinal haemorrhage † 1     
# participants affected / at risk   7/757 (0.92%)   8/761 (1.05%) 
Gastrointestinal ulcer † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Lower gastrointestinal haemorrhage † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Oesophagitis † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Toothache † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Upper gastrointestinal haemorrhage † 1     
# participants affected / at risk   0/757 (0.00%)   3/761 (0.39%) 
General disorders     
Device occlusion † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Hyperthermia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Pain † 1     
# participants affected / at risk   9/757 (1.19%)   7/761 (0.92%) 
Peripheral swelling † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Pyrexia † 1     
# participants affected / at risk   14/757 (1.85%)   29/761 (3.81%) 
Death † 1     
# participants affected / at risk   2/757 (0.26%)   3/761 (0.39%) 
Face oedema † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Influenza like illness † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Mucosal inflammation † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Oedema † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Malaise † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Oedema peripheral † 1     
# participants affected / at risk   3/757 (0.40%)   6/761 (0.79%) 
Sudden death † 1     
# participants affected / at risk   3/757 (0.40%)   0/761 (0.00%) 
Fatigue † 1     
# participants affected / at risk   9/757 (1.19%)   15/761 (1.97%) 
Multi-organ failure † 1     
# participants affected / at risk   1/757 (0.13%)   3/761 (0.39%) 
Performance status decreased † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
General physical health deterioration † 1     
# participants affected / at risk   1/757 (0.13%)   4/761 (0.53%) 
Chest pain † 1     
# participants affected / at risk   8/757 (1.06%)   9/761 (1.18%) 
Condition aggravated † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Generalised oedema † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Disease progression † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Localised oedema † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Asthenia † 1     
# participants affected / at risk   7/757 (0.92%)   13/761 (1.71%) 
Chills † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Hepatobiliary disorders     
Cholecystitis † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Cholecystitis acute † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Cholelithiasis † 1     
# participants affected / at risk   2/757 (0.26%)   1/761 (0.13%) 
Hepatic pain † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Hepatotoxicity † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Immune system disorders     
Hypersensitivity † 1     
# participants affected / at risk   1/757 (0.13%)   3/761 (0.39%) 
Anaphylactic reaction † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Drug hypersensitivity † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Infections and infestations     
Diverticulitis † 1     
# participants affected / at risk   3/757 (0.40%)   1/761 (0.13%) 
Empyema † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Gastroenteritis † 1     
# participants affected / at risk   3/757 (0.40%)   3/761 (0.39%) 
Scrotal abscess † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Bronchitis † 1     
# participants affected / at risk   3/757 (0.40%)   1/761 (0.13%) 
Cellulitis † 1     
# participants affected / at risk   3/757 (0.40%)   9/761 (1.18%) 
Cystitis † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Oesophageal infection † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Peritonitis † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Pyelonephritis acute † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Tooth infection † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Cellulitis of male external genital organ † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Lower respiratory tract infection † 1     
# participants affected / at risk   0/757 (0.00%)   5/761 (0.66%) 
Endocarditis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Infection † 1     
# participants affected / at risk   4/757 (0.53%)   8/761 (1.05%) 
Lobar pneumonia † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Lung infection † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Oral candidiasis † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Respiratory tract infection † 1     
# participants affected / at risk   1/757 (0.13%)   4/761 (0.53%) 
Sepsis † 1     
# participants affected / at risk   6/757 (0.79%)   7/761 (0.92%) 
Upper respiratory tract infection † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Urinary tract infection † 1     
# participants affected / at risk   7/757 (0.92%)   10/761 (1.31%) 
Candida infection † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Clostridium difficile colitis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Gangrene † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Herpes zoster † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Intestinal sepsis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Neutropenic sepsis † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Balanoposthitis infective † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Device related infection † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Encephalitis † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Enterocolitis bacterial † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Fungal oesophagitis † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Influenza † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Pneumonia † 1     
# participants affected / at risk   22/757 (2.91%)   33/761 (4.34%) 
Septic shock † 1     
# participants affected / at risk   3/757 (0.40%)   10/761 (1.31%) 
Urosepsis † 1     
# participants affected / at risk   4/757 (0.53%)   1/761 (0.13%) 
Abscess intestinal † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Bacteraemia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Bronchopneumonia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Gastrointestinal infection † 1     
# participants affected / at risk   1/757 (0.13%)   3/761 (0.39%) 
Pneumonia streptococcal † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Staphylococcal sepsis † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Anal abscess † 1     
# participants affected / at risk   2/757 (0.26%)   1/761 (0.13%) 
Appendicitis † 1     
# participants affected / at risk   3/757 (0.40%)   1/761 (0.13%) 
Clostridium difficile infection † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Device related sepsis † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Erysipelas † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Infective exacerbation of chronic obstructive airways disease † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Neutropenic infection † 1     
# participants affected / at risk   3/757 (0.40%)   3/761 (0.39%) 
Perirectal abscess † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Injury, poisoning and procedural complications     
Fracture † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Gastroenteritis radiation † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Hip fracture † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Radiation proctitis † 1     
# participants affected / at risk   0/757 (0.00%)   4/761 (0.53%) 
Venous injury † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Accidental overdose † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Contusion † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Femoral neck fracture † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Gastrointestinal anastomotic leak † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Infusion related reaction † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Joint injury † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Multiple fractures † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Tracheal obstruction † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Upper limb fracture † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Anastomotic leak † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Clavicle fracture † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Femur fracture † 1     
# participants affected / at risk   2/757 (0.26%)   2/761 (0.26%) 
Lower limb fracture † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Thoracic vertebral fracture † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Ulna fracture † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Procedural complication † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Rib fracture † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Fall † 1     
# participants affected / at risk   3/757 (0.40%)   1/761 (0.13%) 
Spinal compression fracture † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Lumbar vertebral fracture † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Overdose † 1     
# participants affected / at risk   6/757 (0.79%)   11/761 (1.45%) 
Spinal fracture † 1     
# participants affected / at risk   3/757 (0.40%)   0/761 (0.00%) 
Investigations     
Aspartate aminotransferase increased † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Bone marrow myelogram abnormal † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Haemoglobin decreased † 1     
# participants affected / at risk   3/757 (0.40%)   9/761 (1.18%) 
Neutrophil count † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Neutrophil count decreased † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Transaminases increased † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Weight decreased † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Haemoglobin † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Alanine aminotransferase increased † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Clostridium test positive † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Eastern Cooperative Oncology Group performance status worsened † 1     
# participants affected / at risk   0/757 (0.00%)   3/761 (0.39%) 
Platelet count decreased † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Urine output decreased † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Blood creatinine increased † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Metabolism and nutrition disorders     
Malnutrition † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Hyperkalaemia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Hypokalaemia † 1     
# participants affected / at risk   2/757 (0.26%)   3/761 (0.39%) 
Dehydration † 1     
# participants affected / at risk   11/757 (1.45%)   21/761 (2.76%) 
Hypercalcaemia † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Hyponatraemia † 1     
# participants affected / at risk   3/757 (0.40%)   2/761 (0.26%) 
Tumour lysis syndrome † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Fluid overload † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Hypomagnesaemia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Hypophagia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Metabolic acidosis † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Hypoglycaemia † 1     
# participants affected / at risk   4/757 (0.53%)   3/761 (0.39%) 
Decreased appetite † 1     
# participants affected / at risk   4/757 (0.53%)   3/761 (0.39%) 
Hyperglycaemia † 1     
# participants affected / at risk   3/757 (0.40%)   2/761 (0.26%) 
Hypocalcaemia † 1     
# participants affected / at risk   6/757 (0.79%)   4/761 (0.53%) 
Hypophosphataemia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Musculoskeletal and connective tissue disorders     
Muscle spasms † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Neck pain † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Osteonecrosis † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Systemic lupus erythematosus † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Fistula † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Musculoskeletal pain † 1     
# participants affected / at risk   3/757 (0.40%)   1/761 (0.13%) 
Osteonecrosis of jaw † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Bone pain † 1     
# participants affected / at risk   7/757 (0.92%)   4/761 (0.53%) 
Flank pain † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Musculoskeletal chest pain † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Groin pain † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Hypercreatinaemia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Pain in extremity † 1     
# participants affected / at risk   3/757 (0.40%)   3/761 (0.39%) 
Pathological fracture † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Spinal pain † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Arthralgia † 1     
# participants affected / at risk   2/757 (0.26%)   1/761 (0.13%) 
Back pain † 1     
# participants affected / at risk   12/757 (1.59%)   7/761 (0.92%) 
Muscular weakness † 1     
# participants affected / at risk   4/757 (0.53%)   3/761 (0.39%) 
Osteoarthritis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Rotator cuff syndrome † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Adenosquamous cell lung cancer † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Neoplasm progression † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Rectal adenocarcinoma † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Renal neoplasm † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Astrocytoma malignant † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Cancer pain † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Prostate cancer † 1     
# participants affected / at risk   3/757 (0.40%)   2/761 (0.26%) 
Colorectal cancer † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Malignant neoplasm progression † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Basal cell carcinoma † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Metastases to meninges † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Metastatic neoplasm † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Rectal cancer † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Squamous cell carcinoma of skin † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Squamous cell carcinoma of the oral cavity † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Non-small cell lung cancer † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Colorectal cancer recurrent † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Meningioma † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Metastatic squamous cell carcinoma † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Prostate cancer metastatic † 1     
# participants affected / at risk   10/757 (1.32%)   9/761 (1.18%) 
Metastasis † 1     
# participants affected / at risk   2/757 (0.26%)   2/761 (0.26%) 
Nervous system disorders     
Carotid artery stenosis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Nerve root compression † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Paraparesis † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Haemorrhage intracranial † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
IIIrd nerve disorder † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Peripheral motor neuropathy † 1     
# participants affected / at risk   4/757 (0.53%)   1/761 (0.13%) 
Aphasia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Cerebral haematoma † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Cerebral ischaemia † 1     
# participants affected / at risk   0/757 (0.00%)   3/761 (0.39%) 
Cerebrovascular accident † 1     
# participants affected / at risk   4/757 (0.53%)   2/761 (0.26%) 
Depressed level of consciousness † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Headache † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Ataxia † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Coma † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Monoplegia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Neuralgia † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Central nervous system haemorrhage † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Cerebral haemorrhage † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Dysarthria † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Motor dysfunction † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Somnolence † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Ischaemic stroke † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Peripheral sensory neuropathy † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Syncope † 1     
# participants affected / at risk   5/757 (0.66%)   4/761 (0.53%) 
Intracranial pressure increased † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Seizure † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Transient ischaemic attack † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Dizziness † 1     
# participants affected / at risk   2/757 (0.26%)   1/761 (0.13%) 
Spinal cord compression † 1     
# participants affected / at risk   6/757 (0.79%)   4/761 (0.53%) 
Psychiatric disorders     
Agitation † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Disorientation † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Mental status changes † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Depression suicidal † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Anxiety † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Confusional state † 1     
# participants affected / at risk   2/757 (0.26%)   6/761 (0.79%) 
Psychotic disorder † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Renal and urinary disorders     
Acute kidney injury † 1     
# participants affected / at risk   4/757 (0.53%)   8/761 (1.05%) 
Haemoglobinuria † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Haemorrhage urinary tract † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Hydronephrosis † 1     
# participants affected / at risk   3/757 (0.40%)   6/761 (0.79%) 
Renal disorder † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Bladder neck obstruction † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Bladder obstruction † 1     
# participants affected / at risk   3/757 (0.40%)   3/761 (0.39%) 
Renal colic † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Urethral stenosis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Renal impairment † 1     
# participants affected / at risk   3/757 (0.40%)   0/761 (0.00%) 
Urinary bladder haemorrhage † 1     
# participants affected / at risk   1/757 (0.13%)   3/761 (0.39%) 
Nephrotic syndrome † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Ureteric obstruction † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Ureteric stenosis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Urinary bladder polyp † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Urinary retention † 1     
# participants affected / at risk   9/757 (1.19%)   9/761 (1.18%) 
Urinary tract obstruction † 1     
# participants affected / at risk   2/757 (0.26%)   3/761 (0.39%) 
Bladder outlet obstruction † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Dysuria † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Haematuria † 1     
# participants affected / at risk   18/757 (2.38%)   10/761 (1.31%) 
Renal failure † 1     
# participants affected / at risk   5/757 (0.66%)   5/761 (0.66%) 
Obstructive uropathy † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Urinary incontinence † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Urogenital haemorrhage † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Reproductive system and breast disorders     
Benign prostatic hyperplasia † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Prostatic obstruction † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Penile pain † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Oedema genital † 1     
# participants affected / at risk   1/757 (0.13%)   2/761 (0.26%) 
Testicular mass † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Dyspnoea † 1     
# participants affected / at risk   10/757 (1.32%)   21/761 (2.76%) 
Hypoxia † 1     
# participants affected / at risk   1/757 (0.13%)   3/761 (0.39%) 
Pneumothorax † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Productive cough † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Alveolitis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Lung disorder † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Cough † 1     
# participants affected / at risk   1/757 (0.13%)   3/761 (0.39%) 
Interstitial lung disease † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Pulmonary oedema † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Respiratory failure † 1     
# participants affected / at risk   2/757 (0.26%)   7/761 (0.92%) 
Dyspnoea exertional † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Pleural effusion † 1     
# participants affected / at risk   1/757 (0.13%)   19/761 (2.50%) 
Pneumonitis † 1     
# participants affected / at risk   7/757 (0.92%)   7/761 (0.92%) 
Acute pulmonary oedema † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Pulmonary embolism † 1     
# participants affected / at risk   17/757 (2.25%)   5/761 (0.66%) 
Pulmonary hypertension † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Pulmonary congestion † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Pulmonary venous thrombosis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Acute respiratory distress syndrome † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Acute respiratory failure † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Chronic obstructive pulmonary disease † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Lung infiltration † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Skin and subcutaneous tissue disorders     
Peau d'orange † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Rash † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Pyoderma gangrenosum † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Drug eruption † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Vascular disorders     
Deep vein thrombosis † 1     
# participants affected / at risk   10/757 (1.32%)   1/761 (0.13%) 
Hypotension † 1     
# participants affected / at risk   8/757 (1.06%)   3/761 (0.39%) 
Shock haemorrhagic † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Venous thrombosis limb † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Circulatory collapse † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Haematoma † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Aortic dissection † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Haemorrhage † 1     
# participants affected / at risk   1/757 (0.13%)   1/761 (0.13%) 
Vasculitis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Embolism † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Infarction † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Thrombosis † 1     
# participants affected / at risk   0/757 (0.00%)   2/761 (0.26%) 
Vena cava thrombosis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Venous thrombosis † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Hypertension † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Jugular vein thrombosis † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Peripheral vascular disorder † 1     
# participants affected / at risk   0/757 (0.00%)   1/761 (0.13%) 
Phlebitis † 1     
# participants affected / at risk   2/757 (0.26%)   0/761 (0.00%) 
Thrombophlebitis superficial † 1     
# participants affected / at risk   1/757 (0.13%)   0/761 (0.00%) 
Events were collected by systematic assessment
1 Term from vocabulary, MedDRA 18.0




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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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