Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Certolizumab Pegol for the Treatment of Patients With Active Rheumatoid Arthritis (REALISTIC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
UCB Pharma
ClinicalTrials.gov Identifier:
NCT00717236
First received: July 15, 2008
Last updated: March 2, 2012
Last verified: March 2012
Results First Received: March 10, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Certolizumab pegol (CZP)
Other: Placebo

  Participant Flow
  Hide Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
The study started in July 2008 with subjects from the United States, Canada, France, Germany, Italy, the Netherlands, and Spain. The primary completion date occurred in March 2010, with study completion in March 2011.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the 1648 subjects that were screened, 585 subjects had screen failures. Therefore, 1063 subjects were randomized in this study.

Reporting Groups
  Description
Certolizumab Pegol (CZP) 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.

Participant Flow for 2 periods

Period 1:   Double-Blind Period
    Certolizumab Pegol (CZP)     Placebo  
STARTED     851     212  
COMPLETED     771     184  
NOT COMPLETED     80     28  
Adverse Event                 33                 6  
Lack of Efficacy                 6                 6  
Lost to Follow-up                 3                 5  
Withdrawal by Subject                 10                 2  
Loss of efficacy                 3                 0  
Other: Death                 1                 0  
Other: Pregnancy                 1                 0  
Other: Protocol Violation                 2                 0  
Other: Inclusion/Exclusion criteria                 6                 2  
Other: Site withdrew                 2                 0  
Other: Screening failure                 1                 0  
Other: subject withdrew consent                 1                 1  
Other: Abnormal chest X-ray                 2                 1  
Other: History of adenoid grown                 1                 0  
Other: History of cancer                 1                 0  
Other: Sponsor request                 1                 0  
Other: Inappropriate randomization                 1                 0  
Other: Detection of Hepatitis C Virus                 1                 0  
Other: Subject moved                 1                 1  
Other: Stopped taking DMARD                 1                 0  
Other: Prohibited medication taken                 2                 2  
Other: Transportation problems                 0                 1  
Other: Investigator Decision                 0                 1  

Period 2:   Open-Label Period
    Certolizumab Pegol (CZP)     Placebo  
STARTED     771     184  
COMPLETED     646     163  
NOT COMPLETED     125     21  
Adverse Event                 29                 4  
Lack of Efficacy                 30                 8  
Lost to Follow-up                 28                 4  
Withdrawal by Subject                 20                 2  
Loss of Efficacy                 6                 1  
Other: Peripheral Neuropathy                 0                 1  
Other: Lack of Compliance                 1                 1  
Other: History of Basal Cell Carcinoma                 1                 0  
Other: Moved                 1                 0  
Other: Investigator Decision                 1                 0  
Other: Loss of Staff (unblinded)                 1                 0  
Other: Sponsor Request                 3                 0  
Other: Cataract Surgery                 1                 0  
Other: Administration of Golimumab                 1                 0  
Other: Completion Accidently Performed                 1                 0  
Other: Medical Monitor Recommendation                 1                 0  



  Baseline Characteristics
  Hide Baseline Characteristics

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
Certolizumab Pegol (CZP) 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. At Week 12 subjects enter the open label phase and receive 200 mg of CZP every other week for a minimum 16 additional weeks until CZP is commercially available.
Total Total of all reporting groups

Baseline Measures
    Certolizumab Pegol (CZP)     Placebo     Total  
Number of Participants  
[units: participants]
  851     212     1063  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     644     164     808  
>=65 years     207     48     255  
Age  
[units: years]
Mean ± Standard Deviation
  55.4  ± 12.43     53.9  ± 12.66     55.1  ± 12.49  
Gender  
[units: participants]
     
Female     660     169     829  
Male     191     43     234  
Region of Enrollment  
[units: participants]
     
France     14     0     14  
United States     575     141     716  
Canada     65     17     82  
Spain     26     8     34  
Netherlands     4     0     4  
Germany     154     44     198  
Italy     13     2     15  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   American College of Rheumatology 20% (ACR20) Response at Week 12   [ Time Frame: Baseline, Week 12 ]

2.  Secondary:   American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Concomitant Methotrexate (MTX) Use.   [ Time Frame: Baseline, Week 12 ]

3.  Secondary:   American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Concomitant Methotrexate (MTX) Use.   [ Time Frame: Baseline, Week 12 ]

4.  Secondary:   American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Prior Anti-tumor Necrosis (Anti-TNF) Use   [ Time Frame: Baseline, Week 12 ]

5.  Secondary:   American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects Without Prior Anti-tumor Necrosis (Anti-TNF) Use   [ Time Frame: Baseline, Week 12 ]

6.  Secondary:   American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration < 2 Years   [ Time Frame: Baseline, Week 12 ]

7.  Secondary:   American College of Rheumatology 20% (ACR20) Response at Week 12 for Subjects With Disease Duration ≥ 2 Years.   [ Time Frame: Baseline, Week 12 ]

8.  Secondary:   American College of Rheumatology 50% (ACR50) Response at Week 12   [ Time Frame: Baseline, Week 12 ]

9.  Secondary:   American College of Rheumatology 70% (ACR70) Response at Week 12.   [ Time Frame: Baseline, Week 12 ]

10.  Secondary:   Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 12   [ Time Frame: Baseline, Week 12 ]

11.  Secondary:   Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 12   [ Time Frame: Baseline, Week 12 ]

12.  Secondary:   Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 12   [ Time Frame: Baseline, Week 12 ]

13.  Secondary:   DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 12   [ Time Frame: Week 12 ]

14.  Secondary:   SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 12   [ Time Frame: Week 12 ]

15.  Secondary:   CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 12   [ Time Frame: Week 12 ]

16.  Secondary:   Change From Baseline in Tender Joint Count (TJC) at Week 12   [ Time Frame: Baseline, Week 12 ]

17.  Secondary:   Change From Baseline in Swollen Joint Count (SJC) at Week 12   [ Time Frame: Baseline, Week 12 ]

18.  Secondary:   Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 12   [ Time Frame: Baseline, Week 12 ]

19.  Secondary:   Change From Baseline in C-reactive Protein (CRP) at Week 12   [ Time Frame: Baseline, Week 12 ]

20.  Secondary:   Change From Baseline in Patient’s Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 12   [ Time Frame: Baseline, Week 12 ]

21.  Secondary:   Change From Baseline in Patient’s Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 12   [ Time Frame: Baseline, Week 12 ]

22.  Secondary:   Change From Baseline in Physician's Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 12   [ Time Frame: Baseline, Week 12 ]

23.  Secondary:   Time to Sustained American College of Rheumatology 20% (ACR20) Response   [ Time Frame: Baseline up to Week 12 ]

24.  Secondary:   European League Against Rheumatism (EULAR) Response at Week 12   [ Time Frame: Baseline, Week 12 ]

25.  Secondary:   American College of Rheumatology 20% (ACR20) Response at Week 28   [ Time Frame: Baseline, Week 28 ]

26.  Secondary:   American College of Rheumatology 50% (ACR50) Response at Week 28   [ Time Frame: Baseline, Week 28 ]

27.  Secondary:   American College of Rheumatology 70% (ACR70) Response at Week 28   [ Time Frame: Baseline, Week 28 ]

28.  Secondary:   Change From Baseline in DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] at Week 28   [ Time Frame: Baseline, Week 28 ]

29.  Secondary:   Change From Baseline in SDAI (Simplified Disease Activity Index) at Week 28   [ Time Frame: Baseline, Week 28 ]

30.  Secondary:   Change From Baseline in CDAI (Clinical Disease Activity Index) at Week 28   [ Time Frame: Baseline, Week 28 ]

31.  Secondary:   DAS28(CRP) [Disease Activity Score-28 (C-reactive Protein)] Remission (<2.6) at Week 28   [ Time Frame: Week 28 ]

32.  Secondary:   SDAI (Simplified Disease Activity Index) Remission (≤3.3) at Week 28   [ Time Frame: Week 28 ]

33.  Secondary:   CDAI (Clinical Disease Activity Index) Remission (≤2.8) at Week 28   [ Time Frame: Week 28 ]

34.  Secondary:   Change From Baseline in Tender Joint Count (TJC) at Week 28   [ Time Frame: Baseline, Week 28 ]

35.  Secondary:   Change From Baseline in Swollen Joint Count (SJC) at Week 28   [ Time Frame: Baseline, Week 28 ]

36.  Secondary:   Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 28   [ Time Frame: Baseline, Week 28 ]

37.  Secondary:   Change From Baseline in C-reactive Protein (CRP) at Week 28   [ Time Frame: Baseline, Week 28 ]

38.  Secondary:   Change From Baseline in Patient’s Assessment of Arthritis Pain-Visual Analog Scale (PAAP-VAS) at Week 28   [ Time Frame: Baseline, Week 28 ]

39.  Secondary:   Change From Baseline in Patient’s Global Assessment of Disease Activity-Visual Analog Scale (PtGADA-VAS) at Week 28   [ Time Frame: Baseline, Week 28 ]

40.  Secondary:   Change From Baseline in Physician’s Global Assessment of Disease Activity-Visual Analog Scale (PhGADA-VAS) at Week 28   [ Time Frame: Baseline, Week 28 ]


  Serious Adverse Events
  Hide Serious Adverse Events

Time Frame The first two columns refer to the 12-week double blind phase, and an additional 12-week follow up for those who withdrew during the double blind period. The third column displays AEs for the 56-week open label phase and the 12-week safety follow-up.
Additional Description Of the 1063 subjects in the Full Analysis Set (FAS), 1055 are included in the adverse event reporting based upon the Safety Set (SS) population. The Safety Set includes all subjects randomized who received at least 1 dosing.

Reporting Groups
  Description
Certolizumab Pegol (CZP) 400 mg CZP given as two 200 mg subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by 200 mg CZP given as 1 sc injection on Weeks 6, 8, and 10. From Week 12, 200 mg CZP given every other week for a minimum 16 additional weeks until CZP is commercially available.
Placebo Placebo (0.9% saline) given as 2 subcutaneous (sc) injections at Weeks 0, 2, and 4, followed by placebo given as 1 sc injection on Weeks 6, 8, and 10. From Week 12, 200 mg certolizumab pegol (CZP) given as 1 subcutaneous injection every other week for a minimum 16 additional weeks until CZP is commercially available.
Open Label Certolizumab Pegol (CZP) Subjects entering the open label extension at Week 12 receive 200 mg CZP given every other week for a minimum 16 additional weeks until CZP is commercially available.

Serious Adverse Events
    Certolizumab Pegol (CZP)     Placebo     Open Label Certolizumab Pegol (CZP)  
Total, serious adverse events        
# participants affected / at risk     52/846 (6.15%)     12/209 (5.74%)     77/954 (8.07%)  
Blood and lymphatic system disorders        
Anaemia * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     0/954 (0.00%)  
# events     0     1     0  
Lymphadenopathy * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Cardiac disorders        
Coronary artery disease * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Cardiac failure * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     1/954 (0.10%)  
# events     1     0     1  
Acute myocardial infarction * 1      
# participants affected / at risk     2/846 (0.24%)     0/209 (0.00%)     2/954 (0.21%)  
# events     2     0     2  
Arteriospasm coronary * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Myocardial infarction * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     3/954 (0.31%)  
# events     1     0     3  
Artial fibrillation * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     2/954 (0.21%)  
# events     1     0     3  
Cardiac failure congestive * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     3/954 (0.31%)  
# events     0     0     3  
Perocardial effusion * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Supraventricular tachycardia * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Angina Pectoris * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Ear and labyrinth disorders        
Vertigo * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Ear pain * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Gastrointestinal disorders        
Pancreatitis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Abdominal pain * 1      
# participants affected / at risk     2/846 (0.24%)     0/209 (0.00%)     0/954 (0.00%)  
# events     2     0     0  
Nausea * 1      
# participants affected / at risk     1/846 (0.12%)     1/209 (0.48%)     0/954 (0.00%)  
# events     1     1     0  
Vomiting * 1      
# participants affected / at risk     2/846 (0.24%)     0/209 (0.00%)     0/954 (0.00%)  
# events     2     0     0  
Umbilical hernia * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Gastrooesophageal reflux disease * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Colitis ischaemic * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Diarrhoea * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     2  
Impaired gastric emptying * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Large intestine perforation * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Volvulus * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Stomatitis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
General disorders        
Chest pain * 1      
# participants affected / at risk     3/846 (0.35%)     2/209 (0.96%)     1/954 (0.10%)  
# events     3     2     1  
Non-cardiac chest pain * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Impaired healing * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Necrosis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Hepatobiliary disorders        
Cholecystitis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Immune system disorders        
Drug hypersensitivity * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Infections and infestations        
Diverticulitis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     2/954 (0.21%)  
# events     1     0     2  
Bronchopulmonary aspergillosis * 1      
# participants affected / at risk     2/846 (0.24%)     0/209 (0.00%)     0/954 (0.00%)  
# events     3     0     0  
Cellulitis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     5/954 (0.52%)  
# events     1     0     5  
Bursitis infective * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Osteomyelitis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Abscess limb * 1      
# participants affected / at risk     2/846 (0.24%)     0/209 (0.00%)     0/954 (0.00%)  
# events     2     0     0  
Bronchitis * 1      
# participants affected / at risk     2/846 (0.24%)     0/209 (0.00%)     3/954 (0.31%)  
# events     2     0     4  
Pneumonia * 1      
# participants affected / at risk     4/846 (0.47%)     1/209 (0.48%)     8/954 (0.84%)  
# events     4     1     8  
Pneumonia necrotising * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Urosepsis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Staphylococcal infection * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Pharyngitis streptococcal * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     1/954 (0.10%)  
# events     0     1     1  
Upper respiratory tract infection * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Cystitis * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     0/954 (0.00%)  
# events     0     1     0  
Pyelonephritis acute * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Urinary tract infection * 1      
# participants affected / at risk     3/846 (0.35%)     0/209 (0.00%)     3/954 (0.31%)  
# events     3     0     3  
Gastroenteritis viral * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Pyelonephritis * 1      
# participants affected / at risk     1/846 (0.12%)     1/209 (0.48%)     0/954 (0.00%)  
# events     1     1     0  
Clostridial infection * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Gastroenteritis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Ear lobe infection * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Postoperative wound infection * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Pneumonia streptococcal * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Disseminated tuberculosis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Sinusitis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     2  
Gastritis viral * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Injury, poisoning and procedural complications        
Femoral neck fracture * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     0/954 (0.00%)  
# events     0     1     0  
Hip fracture * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Lower limb fracture * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     0/954 (0.00%)  
# events     0     1     0  
Tibia fracture * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Foreign body trauma * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Spinal compression fracture * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Concussion * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Subdural haematoma * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Device breakage * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Gastrointestinal disorder postoperative * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Ankle fracture * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Polytraumatism * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Skin laceration * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Upper limb fracture * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Investigations        
Blood glucose increased * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     1/954 (0.10%)  
# events     1     0     1  
Metabolism and nutrition disorders        
Dehydration * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     3/954 (0.31%)  
# events     1     0     3  
Diabetes mellitus * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     0/954 (0.00%)  
# events     0     1     0  
Hyponatraemia * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Musculoskeletal and connective tissue disorders        
Rheumatoid arthritis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     3/954 (0.31%)  
# events     1     0     3  
Spinal column stenosis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Bursitis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Intervertebral disc protrusion * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     2  
Rotator cuff syndrome * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Arthralgia * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Osteoarthritis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     2  
Neoplasms benign, malignant and unspecified (incl cysts and polyps)        
Breast cancer * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     1/954 (0.10%)  
# events     0     1     1  
Carcinoid tumour * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Hepatic neoplasm * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     0/954 (0.00%)  
# events     0     1     0  
Adenocarcinoma pancreas * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Malignant melanoma * 1      
# participants affected / at risk     1/846 (0.12%)     1/209 (0.48%)     1/954 (0.10%)  
# events     1     1     1  
Sarcoma uterus * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Colon adenoma * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Breast cancer metastatic * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Ovarian granulosa-theca cell tumor * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Mycosis fungoides * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Small cell lung cancer metastatic * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     2  
Basal cell carcinoma * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Uterine leiomyoma * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Nervous system disorders        
Syncope * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     2/954 (0.21%)  
# events     1     0     2  
Brain stem infarction * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Grand mal convulsion * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Dizziness * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Pregnancy, puerperium and perinatal conditions        
Pregnancy * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     1/954 (0.10%)  
# events     1     0     1  
Psychiatric disorders        
Suicide attempt * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Depression * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Renal and urinary disorders        
Bladder prolapse * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Azotaemia * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Renal failure * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     2  
Renal failure acute * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Renal impairment * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Nephrolithiasis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Reproductive system and breast disorders        
Cervical dysplasia * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Respiratory, thoracic and mediastinal disorders        
Dyspnoea exertional * 1      
# participants affected / at risk     0/846 (0.00%)     1/209 (0.48%)     1/954 (0.10%)  
# events     0     1     1  
Asthma * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     1/954 (0.10%)  
# events     1     0     1  
Chronic obstructive pulmonary disease * 1      
# participants affected / at risk     2/846 (0.24%)     0/209 (0.00%)     0/954 (0.00%)  
# events     2     0     0  
Pulmonary oedema * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Dyspnoea * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     1/954 (0.10%)  
# events     1     0     1  
Pneumonitis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Plural effusion * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Pulmonary embolism * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     2  
Skin and subcutaneous tissue disorders        
Angioneurotic oedema * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Urticaria * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Drug eurption * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Skin ulcer * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Surgical and medical procedures        
Gastric bypass * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Synoviorthesis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Vascular disorders        
Hypertensive crisis * 1      
# participants affected / at risk     1/846 (0.12%)     0/209 (0.00%)     0/954 (0.00%)  
# events     1     0     0  
Peripheral artery aneurysm * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Deep vein thrombosis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     2  
Femoral arterial stenosis * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     1/954 (0.10%)  
# events     0     0     1  
Hypertension * 1      
# participants affected / at risk     0/846 (0.00%)     0/209 (0.00%)     2/954 (0.21%)  
# events     0     0     3  
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedDRA (9.0)




  Other Adverse Events


  Limitations and Caveats
  Hide Limitations and Caveats

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
No text entered.


  More Information