Pazopanib Versus Sunitinib in the Treatment of Locally Advanced and/or Metastatic Renal Cell Carcinoma (COMPARZ)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT00720941
First received: July 22, 2008
Last updated: June 19, 2014
Last verified: February 2014
Results First Received: January 4, 2013  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Condition: Carcinoma, Renal Cell
Interventions: Drug: Pazopanib
Drug: Sunitinib

  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
Per protocol amendment, the number of participants (par.) was increased to ~1100 (including all par. enrolled in Studies VEG108844 and VEG113078 [NCT01147822; a substudy in Asian par.]). This summary is a pooled analysis of both studies. 1110 par. were analyzed; 927 from VEG108844 (reflected in the protocol enrollment field), 183 from VEG113078.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were stratified based on Karnofsky Performance Scale scores (70 or 80; 90 or 100), Baseline levels of lactate dehydrogenase (>1.5 versus <=1.5 times the upper limit of normal [ULN]), and previous nephrectomy (yes versus no) and were randomized in a 1:1 ratio to receive either pazopanib or sunitinib.

Reporting Groups
  Description
Pazopanib 800 mg Participants were administered pazopanib 800 milligrams (mg) (2 x 400 mg tablets) orally once daily (OD) continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
Sunitinib 50 mg Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.

Participant Flow:   Overall Study
    Pazopanib 800 mg     Sunitinib 50 mg  
STARTED     557     553  
Ongoing     34     23  
COMPLETED     144     138  
NOT COMPLETED     413     415  
Death                 334                 335  
Protocol Violation                 0                 2  
Lost to Follow-up                 17                 15  
Physician Decision                 1                 5  
Withdrawal by Subject                 27                 35  
Ongoing                 34                 23  



  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
Pazopanib 800 mg Participants were administered pazopanib 800 mg (2 x 400 mg tablets) orally OD continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
Sunitinib 50 mg Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
Total Total of all reporting groups

Baseline Measures
    Pazopanib 800 mg     Sunitinib 50 mg     Total  
Number of Participants  
[units: participants]
  557     553     1110  
Age  
[units: Years]
Mean ± Standard Deviation
  60.9  ± 10.89     61.2  ± 10.98     61.1  ± 10.93  
Gender  
[units: Participants]
     
Female     159     138     297  
Male     398     415     813  
Race/Ethnicity, Customized  
[units: Participants]
     
African American/African Heritage     10     5     15  
American Indian or Alaska Native     3     0     3  
Asian     194     188     382  
White     349     358     707  
American Indian or Alaska Native & White     0     1     1  
Unknown     1     1     2  



  Outcome Measures
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1.  Primary:   Progression-free Survival (PFS)   [ Time Frame: From randomization until the earliest date of disease progression or death (up to Study Week 191) ]

2.  Secondary:   Overall Survival   [ Time Frame: From randomization until death (up to Study Week 268) ]

3.  Secondary:   Number of Participants in the Indicated Categories for Overall Response as Assessed by Independent Review   [ Time Frame: From randomization until the time of a confirmed best response of CR or PR (up to Study Week 167) ]

4.  Secondary:   Time to Response   [ Time Frame: From randomization until the time of the first documented confirmed complete or partial response (up to Study Week 167) ]

5.  Secondary:   Duration of Response (DOR)   [ Time Frame: From the time of the first documented confirmed complete or partial response until disease progression or death, if sooner (up to Study Week 167) ]

6.  Secondary:   Number of Participants (Par.) With Serious Adverse Events (SAEs)/Non-serious Adverse Events (Any Untoward Medical Occurrence in a Par. Administered a Pharmaceutical Product and Which Does Not Necessarily Have a Causal Relationship With This Treatment)   [ Time Frame: From the time of the first dose of study drug to approximately one month after the discontinuation of study drug (up to Study Week 268) ]

7.  Secondary:   Change From Baseline in Functional Assessment of Chronic Illness Therapy–Fatigue (FACIT-F) Scale Scores at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline (predose); Weeks 4, 10, 16, and 22 ]

8.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Disease-related Symptoms-physical (DRS-P) Domain Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

9.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Disease Related Symptoms-emotional (DRS-E) Domain Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

10.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Treatment Side Effects (TSE) Domain Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

11.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Functional Well Being (FWB) Domain Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

12.  Secondary:   Change From Baseline in the FACT-Kidney Symptom Index-19 (FKSI-19) Scale Total Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

13.  Secondary:   Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Scale Worst Soreness Scores at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

14.  Secondary:   Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Mouth and Throat Soreness Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

15.  Secondary:   Change From Baseline in the Supplementary Quality of Life Questions (SQLQ) Limitations Due to Foot Soreness Scores at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Baseline; Weeks 4, 10, 16, and 22 ]

16.  Secondary:   Summary of Analysis for the Cancer Treatment Satisfaction Questionnaire (CTSQ) Score at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Weeks 4, 10, 16, and 22 ]

17.  Secondary:   Medical Resource Utilization (MRU): Assessed as the Mean Number of Non-study Medical Visits, Telephone Consultations, Hospital Days, and Emergency Room (ER) Visits Per 30 Days Through Week 24   [ Time Frame: From Day 1 up to Week 24 ]

18.  Secondary:   MRU: The Mean Number of Laboratory Visits, Radiology Visits, Home Healthcare Visits, and Medical Procedures for Cycles 1-4. MRU Data Collected at Day 28 of Cycles 1-4 (Average of Weeks 4, 10, 16, and 22, Respectively)   [ Time Frame: Weeks 4, 10, 16, and 22 ]


  Serious Adverse Events
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Time Frame Participants were analyzed from the time of the first dose of study drug to approximately one month after the discontinuation of study drug (up to Study Week 268).
Additional Description Serious adverse events (SAEs) and non-serious AEs were collected in the Safety Population, comprised of all randomized participants who received at least one dose of study medication, according to the actual treatment received.

Reporting Groups
  Description
Pazopanib 800 mg Participants were administered pazopanib 800 mg (2 x 400 mg tablets) orally OD continuously. Pazopanib was to be taken at least one hour before or at least two hours after a meal. Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.
Sunitinib 50 mg Participants were administered sunitinib 50 mg orally once daily in 6-week cycles (4 weeks of treatment, followed by 2 weeks without treatment). Participants received study treatment until disease progression, death, unacceptable toxicity, or withdrawal of consent for any other reasons.

Serious Adverse Events
    Pazopanib 800 mg     Sunitinib 50 mg  
Total, serious adverse events      
# participants affected / at risk     230/554 (41.52%)     224/548 (40.88%)  
Blood and lymphatic system disorders      
Anaemia † 1    
# participants affected / at risk     9/554 (1.62%)     9/548 (1.64%)  
Thrombocytopenia † 1    
# participants affected / at risk     4/554 (0.72%)     25/548 (4.56%)  
Febrile neutropenia † 1    
# participants affected / at risk     3/554 (0.54%)     0/548 (0.00%)  
Neutropenia † 1    
# participants affected / at risk     2/554 (0.36%)     7/548 (1.28%)  
Polycythaemia † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Idiopathic thrombocytopenic purpura † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Lymphopenia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Microangiopathic haemolytic anaemia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Cardiac disorders      
Acute myocardial infarction † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Angina pectoris † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Myocardial infarction † 1    
# participants affected / at risk     2/554 (0.36%)     4/548 (0.73%)  
Atrial fibrillation † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Cardiac failure congestive † 1    
# participants affected / at risk     1/554 (0.18%)     4/548 (0.73%)  
Cardiopulmonary failure † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Coronary artery stenosis † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Left ventricular dysfunction † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Palpitations † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Pericardial effusion † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Tachycardia † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Angina unstable † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Atrial thrombosis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Bradycardia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Sick sinus syndrome † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Torsade de pointes † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Ear and labyrinth disorders      
Sudden hearing loss † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Endocrine disorders      
Adrenal insufficiency † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Eye disorders      
Retinal detachment † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Gastrointestinal disorders      
Vomiting † 1    
# participants affected / at risk     7/554 (1.26%)     8/548 (1.46%)  
Nausea † 1    
# participants affected / at risk     6/554 (1.08%)     7/548 (1.28%)  
Diarrhoea † 1    
# participants affected / at risk     5/554 (0.90%)     10/548 (1.82%)  
Pancreatitis † 1    
# participants affected / at risk     5/554 (0.90%)     2/548 (0.36%)  
Abdominal pain † 1    
# participants affected / at risk     3/554 (0.54%)     4/548 (0.73%)  
Duodenal ulcer † 1    
# participants affected / at risk     3/554 (0.54%)     0/548 (0.00%)  
Ileus † 1    
# participants affected / at risk     3/554 (0.54%)     0/548 (0.00%)  
Gastrointestinal haemorrhage † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Rectal haemorrhage † 1    
# participants affected / at risk     2/554 (0.36%)     1/548 (0.18%)  
Small intestinal haemorrhage † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Abdominal pain upper † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Anal fistula † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Anal ulcer haemorrhage † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Ascites † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Colitis † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Large intestine polyp † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Constipation † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Enterocolitis † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Gastric fistula † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Gastritis † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Gastritis erosive † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Glossodynia † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Inguinal hernia † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Intestinal obstruction † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Lower gastrointestinal haemorrhage † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Lumbar hernia † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Peptic ulcer † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Small intestinal obstruction † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Upper gastrointestinal haemorrhage † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Abdominal distension † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Abdominal pain lower † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Duodenal ulcer haemorrhage † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Erosive oesophagitis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Gastric haemorrhage † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Haematemesis † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Haematochezia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Haemorrhoidal haemorrhage † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Obstruction gastric † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Oesophagitis ulcerative † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Pancreatitis acute † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Stomatitis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Swollen tongue † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Gastrointestinal disorder † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
General disorders      
Pyrexia † 1    
# participants affected / at risk     5/554 (0.90%)     14/548 (2.55%)  
Fatigue † 1    
# participants affected / at risk     3/554 (0.54%)     12/548 (2.19%)  
Non-cardiac chest pain † 1    
# participants affected / at risk     3/554 (0.54%)     0/548 (0.00%)  
Asthenia † 1    
# participants affected / at risk     2/554 (0.36%)     4/548 (0.73%)  
Chest pain † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Death † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Disease progression † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Impaired healing † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Pain † 1    
# participants affected / at risk     1/554 (0.18%)     3/548 (0.55%)  
General physical health deterioration † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Malaise † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Pneumatosis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Sudden death † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Hepatobiliary disorders      
Hepatotoxicity † 1    
# participants affected / at risk     8/554 (1.44%)     0/548 (0.00%)  
Hepatic function abnormal † 1    
# participants affected / at risk     7/554 (1.26%)     4/548 (0.73%)  
Cholecystitis † 1    
# participants affected / at risk     2/554 (0.36%)     1/548 (0.18%)  
Cholelithiasis † 1    
# participants affected / at risk     2/554 (0.36%)     1/548 (0.18%)  
Cholecystitis acute † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Drug-induced liver injury † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Gallbladder perforation † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Hepatitis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Hyperbilirubinaemia † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Jaundice cholestatic † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Immune system disorders      
Anaphylactic reaction † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Infections and infestations      
Pneumonia † 1    
# participants affected / at risk     4/554 (0.72%)     6/548 (1.09%)  
Sepsis † 1    
# participants affected / at risk     3/554 (0.54%)     1/548 (0.18%)  
Urinary tract infection † 1    
# participants affected / at risk     3/554 (0.54%)     1/548 (0.18%)  
Abscess † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Anal abscess † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Appendicitis † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Bronchitis † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Cellulitis † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
H1N1 influenza † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Infection † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Lung infection † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Otitis media † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Pneumocystis jiroveci pneumonia † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Pyelonephritis † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Septic shock † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Wound infection † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Bacterial infection † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Febrile infection † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Gastroenteritis † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Herpes zoster † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Lower respiratory tract infection † 1    
# participants affected / at risk     0/554 (0.00%)     3/548 (0.55%)  
Perinephric abscess † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Peritonitis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Pneumonia bacterial † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Pyelonephritis acute † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Renal abscess † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Retroperitoneal abscess † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Salmonella sepsis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Injury, poisoning and procedural complications      
Acetabulum fracture † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Brain herniation † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Contusion † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Craniocerebral injury † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Femur fracture † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Humerus fracture † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Ilium fracture † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Post procedural discharge † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Tibia fracture † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Ankle fracture † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Chemical poisoning † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Fall † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Fracture † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Patella fracture † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Investigations      
Alanine aminotransferase increased † 1    
# participants affected / at risk     35/554 (6.32%)     8/548 (1.46%)  
Aspartate aminotransferase increased † 1    
# participants affected / at risk     17/554 (3.07%)     2/548 (0.36%)  
Lipase increased † 1    
# participants affected / at risk     7/554 (1.26%)     4/548 (0.73%)  
Hepatic enzyme increased † 1    
# participants affected / at risk     6/554 (1.08%)     1/548 (0.18%)  
Gamma-glutamyltransferase increased † 1    
# participants affected / at risk     3/554 (0.54%)     0/548 (0.00%)  
Liver function test abnormal † 1    
# participants affected / at risk     3/554 (0.54%)     0/548 (0.00%)  
Blood bilirubin increased † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Blood creatinine increased † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Neutrophil count decreased † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Blood alkaline phosphatase increased † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Blood glucose decreased † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Blood potassium increased † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Ejection fraction decreased † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Haemoglobin decreased † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Amylase increased † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Blood calcium increased † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Blood creatine phosphokinase increased † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Blood magnesium decreased † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Electrocardiogram QT prolonged † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Platelet count decreased † 1    
# participants affected / at risk     0/554 (0.00%)     9/548 (1.64%)  
Metabolism and nutrition disorders      
Dehydration † 1    
# participants affected / at risk     8/554 (1.44%)     11/548 (2.01%)  
Hypercalcaemia † 1    
# participants affected / at risk     5/554 (0.90%)     1/548 (0.18%)  
Hyponatraemia † 1    
# participants affected / at risk     4/554 (0.72%)     7/548 (1.28%)  
Decreased appetite † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Hypocalcaemia † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Electrolyte imbalance † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Hyperkalaemia † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Hyperlipasaemia † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Hyperuricaemia † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Hypokalaemia † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Hyperamylasaemia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Hypoglycaemia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Hypophosphataemia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Malnutrition † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Hyperglycaemia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Musculoskeletal and connective tissue disorders      
Back pain † 1    
# participants affected / at risk     3/554 (0.54%)     6/548 (1.09%)  
Arthralgia † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Flank pain † 1    
# participants affected / at risk     2/554 (0.36%)     1/548 (0.18%)  
Osteolysis † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Bone pain † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Groin pain † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Muscular weakness † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Pain in extremity † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Fistula † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Haemarthrosis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Intervertebral disc compression † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Musculoskeletal pain † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Pathological fracture † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)      
Colon cancer † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Adenocarcinoma † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Cancer pain † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Endometrial cancer metastatic † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Lipoma † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Metastases to central nervous system † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Metastases to liver † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Metastasis † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Squamous cell carcinoma of skin † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Tumour rupture † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Cholesteatoma † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Gastric cancer † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Malignant melanoma † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Metastases to lung † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Paraneoplastic syndrome † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Parathyroid tumour benign † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Renal cancer metastatic † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Signet-ring cell carcinoma † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Tumour associated fever † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Tumour haemorrhage † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Adenocarcinoma of colon † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Basal cell carcinoma † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Nervous system disorders      
Cerebral haemorrhage † 1    
# participants affected / at risk     4/554 (0.72%)     1/548 (0.18%)  
Spinal cord compression † 1    
# participants affected / at risk     4/554 (0.72%)     3/548 (0.55%)  
Transient ischaemic attack † 1    
# participants affected / at risk     3/554 (0.54%)     1/548 (0.18%)  
Cerebrovascular accident † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Headache † 1    
# participants affected / at risk     2/554 (0.36%)     1/548 (0.18%)  
Anaesthesia † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Central nervous system haemorrhage † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Convulsion † 1    
# participants affected / at risk     2/554 (0.36%)     3/548 (0.55%)  
Dizziness † 1    
# participants affected / at risk     2/554 (0.36%)     1/548 (0.18%)  
Encephalopathy † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Haemorrhage intracranial † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Ischaemic stroke † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Metabolic encephalopathy † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Paraplegia † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Syncope † 1    
# participants affected / at risk     1/554 (0.18%)     4/548 (0.73%)  
Cerebral infarction † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Cerebral ischaemia † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Haemorrhagic cerebral infarction † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Hypoaesthesia † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Lethargy † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Loss of consciousness † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Motor dysfunction † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Paraesthesia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Presyncope † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Subarachnoid haemorrhage † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Tremor † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Psychiatric disorders      
Confusional state † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Mental status changes † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Anxiety † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Emotional distress † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Sleep disorder † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Renal and urinary disorders      
Renal failure acute † 1    
# participants affected / at risk     4/554 (0.72%)     9/548 (1.64%)  
Haematuria † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Proteinuria † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Renal failure † 1    
# participants affected / at risk     1/554 (0.18%)     4/548 (0.73%)  
Renal haemorrhage † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Ureteric obstruction † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Urinary retention † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Nephrotic syndrome † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Renal impairment † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Reproductive system and breast disorders      
Bartholin's cyst † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Penile oedema † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Respiratory, thoracic and mediastinal disorders      
Pulmonary embolism † 1    
# participants affected / at risk     8/554 (1.44%)     8/548 (1.46%)  
Dyspnoea † 1    
# participants affected / at risk     6/554 (1.08%)     8/548 (1.46%)  
Haemoptysis † 1    
# participants affected / at risk     3/554 (0.54%)     2/548 (0.36%)  
Respiratory failure † 1    
# participants affected / at risk     2/554 (0.36%)     2/548 (0.36%)  
Hydropneumothorax † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Hypoxia † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Pleural effusion † 1    
# participants affected / at risk     1/554 (0.18%)     11/548 (2.01%)  
Pleurisy † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Pleuritic pain † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Pneumonitis † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Pneumothorax † 1    
# participants affected / at risk     1/554 (0.18%)     2/548 (0.36%)  
Acute respiratory failure † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Chronic obstructive pulmonary disease † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Cough † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Epistaxis † 1    
# participants affected / at risk     0/554 (0.00%)     6/548 (1.09%)  
Hiccups † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Laryngeal haemorrhage † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Lung infiltration † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Pneumonia aspiration † 1    
# participants affected / at risk     0/554 (0.00%)     2/548 (0.36%)  
Pulmonary artery thrombosis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Skin and subcutaneous tissue disorders      
Palmar-plantar erythrodysaesthesia syndrome † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Angioedema † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Decubitus ulcer † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Dry gangrene † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Rash † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Actinic keratosis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Vascular disorders      
Hypertension † 1    
# participants affected / at risk     6/554 (1.08%)     7/548 (1.28%)  
Deep vein thrombosis † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Hypertensive crisis † 1    
# participants affected / at risk     2/554 (0.36%)     0/548 (0.00%)  
Aortic thrombosis † 1    
# participants affected / at risk     1/554 (0.18%)     0/548 (0.00%)  
Hypotension † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Thrombosis † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Vena cava thrombosis † 1    
# participants affected / at risk     1/554 (0.18%)     1/548 (0.18%)  
Angiodysplasia † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Arterial rupture † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Haematoma † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Orthostatic hypotension † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Temporal ateritis † 1    
# participants affected / at risk     0/554 (0.00%)     1/548 (0.18%)  
Events were collected by systematic assessment
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  Limitations and Caveats
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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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