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A Study to Evaluate the Safety and Efficacy of Ustekinumab Maintenance Therapy in Patients With Moderately to Severely Active Crohn's Disease (IM-UNITI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01369355
Recruitment Status : Completed
First Posted : June 8, 2011
Results First Posted : February 23, 2017
Last Update Posted : October 22, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Crohn's Disease
Colitis
IBD
Inflammatory Bowel Disease
Interventions Drug: Placebo SC
Drug: Placebo IV
Drug: Ustekinumab 90 mg SC q8w
Drug: Ustekinumab 130 mg IV
Drug: Ustekinumab 90 mg SC q12w
Enrollment 1282
Recruitment Details Out of 1282 participants enrolled,1 was excluded from study before assignment to arm/group due to deviation from Good Clinical Practice at 1 study site. Hence 1281 participants were analyzed. Total 397 participants who were in clinical response to ustekinumab induction were randomized in maintenance study and considered as primary population.
Pre-assignment Details Due to a stability issue with the batch of Intravenous (IV) drug (130 mg ustekinumab), in November 2011 sponsor temporarily suspended dosing in induction studies (CRD3001 and CRD3002) and this maintenance study (CRD3003). All 3 studies were restarted with a 90 milligram per milliliter (mg/mL) formulation for IV administration on 17 February 2012.
Arm/Group Title Ustekinumab Induction Responders(UST-I-Rsp)Placebo Maintenance UST-I-Rsp-UST-90 mg Every 12 Weeks (Q12W) Maintenance UST-I-Rsp-UST-90 mg Q8W Maintenance Placebo (PBO)-I-Rsp - PBO Maintenance PBO-I-nonRsp - UST-130mg Intravenous/90mg SC Q12W Maintenance UST-I-nonRsp - UST-90mg Subcutaneously (SC) Q8W Maintenance Placebo Long Term Extension (LTE) UST 90 mg SC Q12W LTE UST 90 mg SC Q8W LTE
Hide Arm/Group Description Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive placebo subcutaneously (SC) every 4 weeks (q4w) in the maintenance study. Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 milligrams (mg) q12w in the maintenance study. Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q8w in the maintenance study. Participants (who were in clinical response to placebo IV at Week 8 of an induction study) received placebo SC q4w in the maintenance study; not randomized. Participants (who were not in clinical response to placebo IV at Week 8 of an induction study) received ustekinumab 130 mg IV on entry into maintenance followed by ustekinumab 90 mg SC q12 weeks beginning at Week 8 of maintenance (if in response); not randomized. Participants (who were not in clinical response to ustekinumab IV at Week 8 of an induction study) received ustekinumab 90 mg SC on entry into maintenance followed by ustekinumab 90 mg SC q8w beginning at Week 8 of maintenance (if in response); not randomized. Participants who received placebo SC in the maintenance study, entered the LTE and continued to receive placebo SC in the LTE study (Week 44 to 272). Participants entered the LTE and continued to receive ustekinumab 90 mg SC q12w in the LTE study (Week 44 to 272). Participants entered the LTE and continued to receive ustekinumab 90 mg SC q8w in the LTE study (Week 44 to 272).
Period Title: Week 0 - Week 44 (Maintenance)
Started 133 132 132 123 285 476 0 0 0
Completed 102 103 101 93 131 204 0 0 0
Not Completed 31 29 31 30 154 272 0 0 0
Reason Not Completed
Adverse Event             9             12             6             7             14             25             0             0             0
Lack of Efficacy             15             14             15             15             126             217             0             0             0
Protocol Violation             0             1             1             0             0             2             0             0             0
Lost to Follow-up             1             0             1             2             5             6             0             0             0
Withdrawal by Subject             6             2             7             6             8             22             0             0             0
Other             0             0             1             0             1             0             0             0             0
Period Title: Long-term Extension (Week 44-272)
Started 0 0 0 0 0 0 151 213 354
Completed 0 0 0 0 0 0 0 107 183
Not Completed 0 0 0 0 0 0 151 106 171
Reason Not Completed
Adverse Event             0             0             0             0             0             0             15             29             53
Death             0             0             0             0             0             0             0             1             3
Lack of Efficacy             0             0             0             0             0             0             12             26             29
Protocol Violation             0             0             0             0             0             0             0             1             2
Physician Decision             0             0             0             0             0             0             1             5             11
Lost to Follow-up             0             0             0             0             0             0             1             5             9
Withdrawal by Subject             0             0             0             0             0             0             12             30             47
Other             0             0             0             0             0             0             110             9             17
Arm/Group Title Ustekinumab Induction Responders(UST-I-Rsp)Placebo Maintenance UST-I-Rsp-UST-90 mg Every 12 Weeks (Q12W) Maintenance UST-I-Rsp-UST-90 mg Q8W Maintenance Placebo (PBO)-I-Rsp - PBO Maintenance PBO-I-nonRsp - UST-130mg Intravenous/90mg SC Q12W Maintenance UST-I-nonRsp - UST-90mg Subcutaneously (SC) Q8W Maintenance Total
Hide Arm/Group Description Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive placebo subcutaneously (SC) every 4 weeks (q4w) in the maintenance study. Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 milligrams (mg) q12w in the maintenance study. Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q8w in the maintenance study. Participants (who were in clinical response to placebo IV at Week 8 of an induction study) received placebo SC q4w in the maintenance study; not randomized. Participants (who were not in clinical response to placebo IV at Week 8 of an induction study) received ustekinumab 130 mg IV on entry into maintenance followed by ustekinumab 90 mg SC q12 weeks beginning at Week 8 of maintenance (if in response); not randomized. Participants (who were not in clinical response to ustekinumab IV at Week 8 of an induction study) received ustekinumab 90 mg SC on entry into maintenance followed by ustekinumab 90 mg SC q8w beginning at Week 8 of maintenance (if in response); not randomized. Total of all reporting groups
Overall Number of Baseline Participants 133 132 132 123 285 476 1281
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 133 participants 132 participants 132 participants 123 participants 285 participants 476 participants 1281 participants
39.5  (12.69) 38.6  (13.65) 37.9  (13.2) 39.1  (12.46) 39  (12.33) 37.4  (12.5) 38.3  (12.68)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 132 participants 132 participants 123 participants 285 participants 476 participants 1281 participants
Female
74
  55.6%
74
  56.1%
76
  57.6%
64
  52.0%
149
  52.3%
275
  57.8%
712
  55.6%
Male
59
  44.4%
58
  43.9%
56
  42.4%
59
  48.0%
136
  47.7%
201
  42.2%
569
  44.4%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 133 participants 132 participants 132 participants 123 participants 285 participants 476 participants 1281 participants
Australia
4
   3.0%
2
   1.5%
3
   2.3%
4
   3.3%
10
   3.5%
15
   3.2%
38
   3.0%
Austria
1
   0.8%
3
   2.3%
1
   0.8%
0
   0.0%
0
   0.0%
1
   0.2%
6
   0.5%
Belgium
2
   1.5%
4
   3.0%
1
   0.8%
1
   0.8%
7
   2.5%
16
   3.4%
31
   2.4%
Bulgaria
5
   3.8%
2
   1.5%
2
   1.5%
4
   3.3%
1
   0.4%
7
   1.5%
21
   1.6%
Brazil
1
   0.8%
1
   0.8%
3
   2.3%
2
   1.6%
2
   0.7%
3
   0.6%
12
   0.9%
Canada
10
   7.5%
4
   3.0%
12
   9.1%
5
   4.1%
17
   6.0%
44
   9.2%
92
   7.2%
Denmark
1
   0.8%
2
   1.5%
1
   0.8%
0
   0.0%
0
   0.0%
0
   0.0%
4
   0.3%
Spain
1
   0.8%
0
   0.0%
1
   0.8%
0
   0.0%
0
   0.0%
1
   0.2%
3
   0.2%
France
6
   4.5%
8
   6.1%
9
   6.8%
1
   0.8%
13
   4.6%
27
   5.7%
64
   5.0%
United Kingdom
4
   3.0%
7
   5.3%
5
   3.8%
7
   5.7%
15
   5.3%
29
   6.1%
67
   5.2%
Croatia
1
   0.8%
1
   0.8%
0
   0.0%
1
   0.8%
0
   0.0%
1
   0.2%
4
   0.3%
Hungary
11
   8.3%
8
   6.1%
8
   6.1%
10
   8.1%
14
   4.9%
13
   2.7%
64
   5.0%
Ireland
0
   0.0%
0
   0.0%
1
   0.8%
0
   0.0%
0
   0.0%
0
   0.0%
1
   0.1%
Iceland
1
   0.8%
1
   0.8%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   0.2%
Israel
3
   2.3%
1
   0.8%
0
   0.0%
1
   0.8%
2
   0.7%
8
   1.7%
15
   1.2%
Italy
6
   4.5%
2
   1.5%
2
   1.5%
1
   0.8%
4
   1.4%
8
   1.7%
23
   1.8%
Japan
4
   3.0%
8
   6.1%
9
   6.8%
4
   3.3%
18
   6.3%
31
   6.5%
74
   5.8%
Korea, Democratic People'S Republic Of
3
   2.3%
3
   2.3%
2
   1.5%
2
   1.6%
5
   1.8%
7
   1.5%
22
   1.7%
Netherlands
4
   3.0%
4
   3.0%
4
   3.0%
1
   0.8%
9
   3.2%
14
   2.9%
36
   2.8%
New Zealand
3
   2.3%
5
   3.8%
2
   1.5%
1
   0.8%
1
   0.4%
3
   0.6%
15
   1.2%
Poland
3
   2.3%
5
   3.8%
6
   4.5%
6
   4.9%
6
   2.1%
10
   2.1%
36
   2.8%
Russia
2
   1.5%
2
   1.5%
3
   2.3%
5
   4.1%
1
   0.4%
4
   0.8%
17
   1.3%
Serbia
2
   1.5%
7
   5.3%
4
   3.0%
3
   2.4%
2
   0.7%
1
   0.2%
19
   1.5%
United States
41
  30.8%
42
  31.8%
40
  30.3%
50
  40.7%
124
  43.5%
198
  41.6%
495
  38.6%
South Africa
5
   3.8%
2
   1.5%
5
   3.8%
7
   5.7%
5
   1.8%
7
   1.5%
31
   2.4%
Czech Republic
0
   0.0%
0
   0.0%
1
   0.8%
0
   0.0%
2
   0.7%
2
   0.4%
5
   0.4%
Germany
9
   6.8%
8
   6.1%
7
   5.3%
7
   5.7%
27
   9.5%
26
   5.5%
84
   6.6%
1.Primary Outcome
Title Number of Participants With Clinical Remission at Week 44
Hide Description Clinical remission at Week 44 was defined as a Crohn's Disease Activity Index (CDAI) score of <150 points (in general, CDAI score ranges from 0 to approximately 600; higher score indicates higher disease activities). CDAI was assessed by collecting information on 8 different Crohn's disease-related variables (extra-intestinal manifestations, abdominal mass, weight, hematocrit, total number of liquid stools, abdominal pain/cramping, use of antidiarrheal drug(s) and/or opiates, and general well-being). A decrease in CDAI over time indicates improvement in disease activity.
Time Frame Week 44
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis population in this study was randomized participants (i.e., participants who were in clinical response to ustekinumab induction dosing at Week 8 from one of the induction studies CRD3001 and CRD3002) after study restart.
Arm/Group Title Placebo Subcutaneously (SC) Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w) Ustekinumab 90 mg SC q8w
Hide Arm/Group Description:
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive placebo subcutaneously (SC) every 4 weeks (q4w) in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q12w in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q8w in the maintenance study.
Overall Number of Participants Analyzed 131 129 128
Measure Type: Number
Unit of Measure: participants
47 63 68
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.040
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2-sided Cochran-Mantel-Haenszel chi-square test, stratified by clinical remission at Week 0, ustekinumab induction dose and the induction study.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 mg SC q8w
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.005
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2-sided Cochran-Mantel-Haenszel chi-square test, stratified by clinical remission at Week 0, ustekinumab induction dose and the induction study.
2.Secondary Outcome
Title Number of Participants With Clinical Response at Week 44
Hide Description Clinical response at Week 44 was defined as a reduction from baseline in the Crohn's Disease Activity Index (CDAI) score of greater than or equal (>=) 100 points. Participants with a baseline CDAI score of > = 220 to less than or equal (< =) 248 were considered to be in clinical response if a CDAI score of less than (<) 150 was attained. A CDAI score of less than 150 indicates clinical remission. A decrease in CDAI score over time indicates improvement in disease activity.
Time Frame Week 44
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis population in this study was randomized participants (i.e., participants who were in clinical response to ustekinumab induction dosing at Week 8 from one of the induction studies CRD3001 and CRD3002) after study restart.
Arm/Group Title Placebo Subcutaneously (SC) Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w) Ustekinumab 90 mg SC q8w
Hide Arm/Group Description:
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive placebo subcutaneously (SC) every 4 weeks (q4w) in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q12w in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q8w in the maintenance study.
Overall Number of Participants Analyzed 131 129 128
Measure Type: Number
Unit of Measure: participants
58 75 76
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.033
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2-sided Cochran-Mantel-Haenszel chi-square test, stratified by clinical remission at Week 0, ustekinumab induction dose and the induction study.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 mg SC q8w
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.018
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2-sided Cochran-Mantel-Haenszel chi-square test, stratified by clinical remission at Week 0, ustekinumab induction dose and the induction study.
3.Secondary Outcome
Title Number of Participants in Clinical Remission at Week 44 Among Participants in Clinical Remission to Ustekinumab at Week 0 of Maintenance Study
Hide Description Clinical remission at week 44 was defined as a CDAI score of < 150 points among participants in clinical remission to ustekinumab at week 0 of maintenance study.
Time Frame Week 44
Hide Outcome Measure Data
Hide Analysis Population Description
Analysis population included all randomized participants after the study was restarted (who were in clinical remission at Week 0 of maintenance study). 'N' (number of participants analyzed) signifies those participants who were evaluable for this outcome measure.
Arm/Group Title Placebo Subcutaneously (SC) Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w) Ustekinumab 90 mg SC q8w
Hide Arm/Group Description:
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive placebo subcutaneously (SC) every 4 weeks (q4w) in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q12w in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q8w in the maintenance study.
Overall Number of Participants Analyzed 79 78 78
Measure Type: Number
Unit of Measure: participants
36 44 52
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.189
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2-sided Cochran-Mantel-Haenszel chi-square test, stratified by ustekinumab induction dose and the induction study.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 mg SC q8w
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2-sided Cochran-Mantel-Haenszel chi-square test, stratified by ustekinumab induction dose and the induction study.
4.Secondary Outcome
Title Number of Participants With Corticosteroid-free Remission at Week 44
Hide Description Corticosteroid-free remission at Week 44 was defined as a CDAI score of <150 points without receiving corticosteroids at Week 44.
Time Frame Week 44
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis population in this study was randomized participants (i.e., participants who were in clinical response to ustekinumab induction dosing at Week 8 from one of the induction studies CRD3001 and CRD3002) after study restart.
Arm/Group Title Placebo Subcutaneously (SC) Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w) Ustekinumab 90 mg SC q8w
Hide Arm/Group Description:
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive placebo subcutaneously (SC) every 4 weeks (q4w) in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q12w in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q8w in the maintenance study.
Overall Number of Participants Analyzed 131 129 128
Measure Type: Number
Unit of Measure: participants
39 55 60
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.035
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2-sided Cochran-Mantel-Haenszel chi-square test, stratified by clinical remission at Week 0, ustekinumab induction dose and the induction study.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 mg SC q8w
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.004
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2-sided Cochran-Mantel-Haenszel chi-square test, stratified by clinical remission at Week 0, ustekinumab induction dose and the induction study.
5.Secondary Outcome
Title Number of Participants in Clinical Remission at Week 44 in the Subset of Participants Who Were Refractory or Intolerant to Tumor Necrosis Factor (TNF) Antagonist Therapy
Hide Description Clinical remission at Week 44 was defined as a CDAI score of <150 points in the subset of participants who were refractory or Intolerant to tumor necrosis factor antagonist therapy.
Time Frame Week 44
Hide Outcome Measure Data
Hide Analysis Population Description
The primary efficacy analysis population in this study was randomized participants (i.e., participants who were in clinical response to ustekinumab induction dosing at Week 8 from one of the induction studies CRD3001 and CRD3002) after study restart.
Arm/Group Title Placebo Subcutaneously (SC) Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w) Ustekinumab 90 mg SC q8w
Hide Arm/Group Description:
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive placebo subcutaneously (SC) every 4 weeks (q4w) in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q12w in the maintenance study.
Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) randomized to receive ustekinumab SC 90 mg q8w in the maintenance study.
Overall Number of Participants Analyzed 61 57 56
Measure Type: Number
Unit of Measure: participants
16 22 23
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 Milligram (mg) SC Every 12 Weeks (q12w)
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.140
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2 sided Cochran-Mantel-Haenszel chi-square test, stratified by clinical remission status at Week 0 and ustekinumab induction dose.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo Subcutaneously (SC), Ustekinumab 90 mg SC q8w
Comments [Not Specified]
Type of Statistical Test Superiority or Other (legacy)
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.102
Comments A fixed sequence testing procedure was used to control alpha at 0.05 over the outcome measures.
Method Cochran-Mantel-Haenszel chi-square test
Comments 2 sided Cochran-Mantel-Haenszel chi-square test, stratified by clinical remission status at Week 0 and ustekinumab induction dose.
Time Frame Up to Week 272
Adverse Event Reporting Description Safety was analyzed for all treated participants who received at least 1 administration of study agent in the maintenance (Week 0-44) and LTE study (Week 44-272).
 
Arm/Group Title Ustekinumab Induction Responders(USTIRsp) Placebo Maintenance UST -I-Rsp -PBO Maintenance -UST-90mg SC Q8W- Maintenance UST-I-Rsp-UST 90 mg SC Every 12 Weeks (Q12W) Maintenance UST-I-Rsp-UST 90 mg SC Q12W/Q8W Maintenance UST-I-Rsp-UST 90 mg SC Q8W Maintenance UST IV-I-Rsp-UST-90mg Maintenance-UST-90mg SC Q8W Maintenance Placebo (PBO)-I-Rsp PBO Maintenance PBO-I-nonRsp- UST-130mg Intravenous/90mg SC Q12W Maintenance UST IV-I-nonRsp - UST-90 mg SC Q8W Maintenance Placebo Long Term Extension (LTE) UST 90 mg SC Q12W LTE UST 90 mg SC Q8W LTE
Hide Arm/Group Description Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) received placebo subcutaneously (SC) every 4 weeks (q4w) in the maintenance study (includes events up to the time of loss of response). Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) received placebo SC and had dose adjustment to ustekinumab SC 90 mg q8w (includes events from the time of loss of response onward). Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) received ustekinumab SC 90 milligrams (mg) q12w in the maintenance study (includes events up to the time of loss of response). Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) received ustekinumab SC 90 mg q12w and had dose adjustment to ustekinumab SC 90 mg q8w in the maintenance study (includes events from the time of loss of response onward). Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) received ustekinumab SC 90 mg q8w (includes events up to the time of loss of response). Participants (who were in clinical response to ustekinumab IV at Week 8 of an induction study) received ustekinumab SC 90 mg q8 weeks and remained on ustekinumab 90 mg q8w upon loss of response (includes events from the time of loss of response onward). Participants (who were in clinical response to placebo IV at Week 8 of an induction study) received placebo SC; not randomized. Participants (who were not in clinical response to placebo IV at Week 8 of an induction study) received ustekinumab 130 mg IV on entry into maintenance followed by ustekinumab 90 mg SC q12 weeks beginning at Week 8 of maintenance (if in response); not randomized. Participants (who were not in clinical response to ustekinumab IV at Week 8 of an induction study) received ustekinumab 90 mg SC on entry into maintenance followed by ustekinumab 90 mg SC q8w beginning at Week 8 of maintenance (if in response); not randomized. Participants who received placebo SC in the maintenance study, entered the LTE and continued to receive placebo SC in the LTE study (Week 44 to 272). Participants entered the LTE and continued to receive ustekinumab 90 mg SC q12w in the LTE study (Week 44 to 272). Participants entered the LTE and continued to receive ustekinumab 90 mg SC q8w in the LTE study (Week 44 to 272).
All-Cause Mortality
Ustekinumab Induction Responders(USTIRsp) Placebo Maintenance UST -I-Rsp -PBO Maintenance -UST-90mg SC Q8W- Maintenance UST-I-Rsp-UST 90 mg SC Every 12 Weeks (Q12W) Maintenance UST-I-Rsp-UST 90 mg SC Q12W/Q8W Maintenance UST-I-Rsp-UST 90 mg SC Q8W Maintenance UST IV-I-Rsp-UST-90mg Maintenance-UST-90mg SC Q8W Maintenance Placebo (PBO)-I-Rsp PBO Maintenance PBO-I-nonRsp- UST-130mg Intravenous/90mg SC Q12W Maintenance UST IV-I-nonRsp - UST-90 mg SC Q8W Maintenance Placebo Long Term Extension (LTE) UST 90 mg SC Q12W LTE UST 90 mg SC Q8W LTE
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/133 (0.00%)   0/51 (0.00%)   0/132 (0.00%)   0/29 (0.00%)   0/131 (0.00%)   0/29 (0.00%)   0/123 (0.00%)   0/285 (0.00%)   0/476 (0.00%)   0/151 (0.00%)   2/213 (0.94%)   4/354 (1.13%) 
Hide Serious Adverse Events
Ustekinumab Induction Responders(USTIRsp) Placebo Maintenance UST -I-Rsp -PBO Maintenance -UST-90mg SC Q8W- Maintenance UST-I-Rsp-UST 90 mg SC Every 12 Weeks (Q12W) Maintenance UST-I-Rsp-UST 90 mg SC Q12W/Q8W Maintenance UST-I-Rsp-UST 90 mg SC Q8W Maintenance UST IV-I-Rsp-UST-90mg Maintenance-UST-90mg SC Q8W Maintenance Placebo (PBO)-I-Rsp PBO Maintenance PBO-I-nonRsp- UST-130mg Intravenous/90mg SC Q12W Maintenance UST IV-I-nonRsp - UST-90 mg SC Q8W Maintenance Placebo Long Term Extension (LTE) UST 90 mg SC Q12W LTE UST 90 mg SC Q8W LTE
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/133 (16.54%)   7/51 (13.73%)   16/132 (12.12%)   5/29 (17.24%)   13/131 (9.92%)   6/29 (20.69%)   19/123 (15.45%)   47/285 (16.49%)   77/476 (16.18%)   26/151 (17.22%)   68/213 (31.92%)   99/354 (27.97%) 
Blood and lymphatic system disorders                         
Anaemia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Iron Deficiency Anaemia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Lymphadenitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Cardiac disorders                         
Acute Myocardial Infarction * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  2/213 (0.94%)  0/354 (0.00%) 
Angina Pectoris * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Aortic Valve Incompetence * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Atrial Fibrillation * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Cardio-Respiratory Arrest * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Cardiomyopathy * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Coronary Artery Disease * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  2/213 (0.94%)  0/354 (0.00%) 
Myocardial Infarction * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Congenital, familial and genetic disorders                         
Fibrous Dysplasia of Bone * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Endocrine disorders                         
Adrenal Insufficiency * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Eye disorders                         
Chorioretinopathy * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Retinal Detachment * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Strabismus * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Gastrointestinal disorders                         
Abdominal Adhesions * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Abdominal Discomfort * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Abdominal Hernia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  1/29 (3.45%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Abdominal Pain * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  2/151 (1.32%)  1/213 (0.47%)  5/354 (1.41%) 
Abdominal Pain Lower * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Anal Fissure * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Anal Fistula * 1  2/133 (1.50%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  2/285 (0.70%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Colitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Colon Dysplasia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Constipation * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  1/354 (0.28%) 
Crohn's Disease * 1  7/133 (5.26%)  4/51 (7.84%)  5/132 (3.79%)  3/29 (10.34%)  4/131 (3.05%)  3/29 (10.34%)  6/123 (4.88%)  15/285 (5.26%)  30/476 (6.30%)  12/151 (7.95%)  17/213 (7.98%)  32/354 (9.04%) 
Cyclic Vomiting Syndrome * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Diarrhoea * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  1/213 (0.47%)  1/354 (0.28%) 
Dyspepsia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Dysphagia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Enterocutaneous Fistula * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Enterovesical Fistula * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Epiploic Appendagitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Faecaloma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  2/285 (0.70%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Fistula of Small Intestine * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Gastric Ulcer Haemorrhage * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Gastritis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Gastrointestinal Haemorrhage * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  1/29 (3.45%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  3/213 (1.41%)  0/354 (0.00%) 
Haematemesis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Haematochezia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  1/213 (0.47%)  0/354 (0.00%) 
Haemorrhoidal Haemorrhage * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  1/354 (0.28%) 
Ileal Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  1/354 (0.28%) 
Inflammatory Bowel Disease * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Intestinal Obstruction * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  1/151 (0.66%)  1/213 (0.47%)  0/354 (0.00%) 
Intestinal Perforation * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Intestinal Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  2/476 (0.42%)  0/151 (0.00%)  0/213 (0.00%)  2/354 (0.56%) 
Large Intestinal Obstruction * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Large Intestinal Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  2/131 (1.53%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Large Intestine Perforation * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Large Intestine Polyp * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Lower Gastrointestinal Haemorrhage * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Mallory-Weiss Syndrome * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Melaena * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Oesophageal Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Rectal Prolapse * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Rectal Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Small Intestinal Obstruction * 1  0/133 (0.00%)  1/51 (1.96%)  1/132 (0.76%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  1/123 (0.81%)  2/285 (0.70%)  10/476 (2.10%)  4/151 (2.65%)  6/213 (2.82%)  10/354 (2.82%) 
Small Intestinal Perforation * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Small Intestinal Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  1/151 (0.66%)  1/213 (0.47%)  1/354 (0.28%) 
Tooth Impacted * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Umbilical Hernia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
General disorders                         
Asthenia * 1  0/133 (0.00%)  1/51 (1.96%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Chest Pain * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Dysplasia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Incarcerated Hernia * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Non-Cardiac Chest Pain * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  1/29 (3.45%)  0/123 (0.00%)  0/285 (0.00%)  2/476 (0.42%)  0/151 (0.00%)  0/213 (0.00%)  2/354 (0.56%) 
Oedema Peripheral * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Pyrexia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  2/354 (0.56%) 
Sudden Death * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Hepatobiliary disorders                         
Bile Duct Stone * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Cholecystitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  1/29 (3.45%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  3/354 (0.85%) 
Immune system disorders                         
Anaphylactic Reaction * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Infections and infestations                         
Abdominal Abscess * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  1/476 (0.21%)  0/151 (0.00%)  2/213 (0.94%)  1/354 (0.28%) 
Abdominal Infection * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Abscess Intestinal * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Acarodermatitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Acute Sinusitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Anal Abscess * 1  1/133 (0.75%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  3/285 (1.05%)  3/476 (0.63%)  1/151 (0.66%)  6/213 (2.82%)  3/354 (0.85%) 
Anal Fistula Infection * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Appendicitis * 1  0/133 (0.00%)  0/51 (0.00%)  2/132 (1.52%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Bacteraemia * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Bronchitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Campylobacter Gastroenteritis * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Cellulitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  2/213 (0.94%)  1/354 (0.28%) 
Clostridium Difficile Colitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  1/285 (0.35%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  1/354 (0.28%) 
Clostridium Difficile Infection * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Cytomegalovirus Colitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  0/354 (0.00%) 
Cytomegalovirus Viraemia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Device Related Infection * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Diverticulitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  2/354 (0.56%) 
Gastroenteritis * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  1/476 (0.21%)  1/151 (0.66%)  1/213 (0.47%)  2/354 (0.56%) 
Gastroenteritis Viral * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Hepatitis Infectious Mononucleosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Influenza * 1  0/133 (0.00%)  1/51 (1.96%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Liver Abscess * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  0/354 (0.00%) 
Lower Respiratory Tract Infection * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Mastitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Myringitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Ophthalmic Herpes Zoster * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Parainfluenzae Virus Infection * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Perirectal Abscess * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  2/354 (0.56%) 
Peritonitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  1/29 (3.45%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Pneumonia * 1  2/133 (1.50%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  1/131 (0.76%)  1/29 (3.45%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  2/213 (0.94%)  2/354 (0.56%) 
Pneumonia Pneumococcal * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  1/29 (3.45%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Pneumonia Staphylococcal * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Postoperative Abscess * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  1/354 (0.28%) 
Postoperative Wound Infection * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Pseudomembranous Colitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Pyelonephritis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  2/354 (0.56%) 
Rectal Abscess * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  0/354 (0.00%) 
Sepsis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  1/213 (0.47%)  1/354 (0.28%) 
Septic Shock * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Sialoadenitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Tonsillitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Tubo-Ovarian Abscess * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Vaginal Abscess * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Vascular Device Infection * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Viral Infection * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Wound Abscess * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Injury, poisoning and procedural complications                         
Alcohol Poisoning * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Allergic Transfusion Reaction * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Anastomotic Haemorrhage * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Anastomotic Leak * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Concussion * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Contusion * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Forearm Fracture * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Gastrointestinal Anastomotic Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Heat Stroke * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Humerus Fracture * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Intestinal Anastomosis Complication * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  1/151 (0.66%)  0/213 (0.00%)  1/354 (0.28%) 
Ligament Rupture * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Ligament Sprain * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Meniscus Injury * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Muscle Injury * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Procedural Intestinal Perforation * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  0/354 (0.00%) 
Procedural Pain * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Seroma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Sternal Injury * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Thoracic Vertebral Fracture * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Investigations                         
Blood Electrolytes Abnormal * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Electrocardiogram Abnormal * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Faecal Volume Increased * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Hepatic Enzyme Increased * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Troponin Increased * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Metabolism and nutrition disorders                         
Dehydration * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  2/213 (0.94%)  3/354 (0.85%) 
Electrolyte Imbalance * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Hypokalaemia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  1/354 (0.28%) 
Hyponatraemia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Malnutrition * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  2/285 (0.70%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Musculoskeletal and connective tissue disorders                         
Arthralgia * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Back Pain * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Costochondritis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Dactylitis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Fibromyalgia * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Intervertebral Disc Protrusion * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Intervertebral Disc Space Narrowing * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Lumbar Spinal Stenosis * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Osteoarthritis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  3/354 (0.85%) 
Polyarthritis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Rotator Cuff Syndrome * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  1/29 (3.45%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Spinal Osteoarthritis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Spinal Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                         
Benign Neoplasm of Thyroid Gland * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Chronic Myeloid Leukaemia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Endometrial Adenocarcinoma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Fibroadenoma of Breast * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Lentigo Maligna * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Meningioma * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Ovarian Adenoma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Pancreatic Carcinoma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Papillary Thyroid Cancer * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  0/213 (0.00%)  0/354 (0.00%) 
Renal Cell Carcinoma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Seminoma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Small Intestine Adenocarcinoma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Uterine Leiomyoma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  1/354 (0.28%) 
Nervous system disorders                         
Cerebral Infarction * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Dementia with Lewy Bodies * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Headache * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Idiopathic Intracranial Hypertension * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Intracranial Aneurysm * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Ischaemic Stroke * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Migraine * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Paraesthesia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Radiculopathy * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Seizure * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Subarachnoid Haemorrhage * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Syncope * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Transient Ischaemic Attack * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  2/354 (0.56%) 
Trigeminal Neuralgia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Pregnancy, puerperium and perinatal conditions                         
Abortion Spontaneous * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  3/213 (1.41%)  3/354 (0.85%) 
Premature Delivery * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Premature Labour * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Psychiatric disorders                         
Depression * 1  0/133 (0.00%)  1/51 (1.96%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  1/476 (0.21%)  1/151 (0.66%)  0/213 (0.00%)  0/354 (0.00%) 
Hallucination * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Suicidal Ideation * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Suicide Attempt * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Renal and urinary disorders                         
Acute Kidney Injury * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
End Stage Renal Disease * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Nephrolithiasis * 1  0/133 (0.00%)  1/51 (1.96%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  1/151 (0.66%)  2/213 (0.94%)  1/354 (0.28%) 
Renal Colic * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Renal Tubular Necrosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Ureterolithiasis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Urinary Retention * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Reproductive system and breast disorders                         
Adenomyosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Bartholin's Cyst * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Female Genital Tract Fistula * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Menorrhagia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Pelvic Congestion * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Uterine Prolapse * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  1/476 (0.21%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Respiratory, thoracic and mediastinal disorders                         
Asphyxia * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Chronic Obstructive Pulmonary Disease * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Nasal Polyps * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Pulmonary Embolism * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  1/151 (0.66%)  1/213 (0.47%)  0/354 (0.00%) 
Pulmonary Granuloma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Pulmonary Haematoma * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Skin and subcutaneous tissue disorders                         
Pustular Psoriasis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Stevens-Johnson Syndrome * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Social circumstances                         
Breast Prosthesis User * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Miscarriage of Partner * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  1/123 (0.81%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Substance Abuser * 1  1/133 (0.75%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Surgical and medical procedures                         
Abdominal Hernia Repair * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Ileostomy Closure * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Knee Arthroplasty * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Pelvic Pouch Procedure * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Rotator Cuff Repair * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
Vascular disorders                         
Aortic Aneurysm * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Aortic Dissection * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Aortic Stenosis * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  1/354 (0.28%) 
Deep Vein Thrombosis * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  1/285 (0.35%)  2/476 (0.42%)  0/151 (0.00%)  0/213 (0.00%)  2/354 (0.56%) 
Essential Hypertension * 1  0/133 (0.00%)  0/51 (0.00%)  1/132 (0.76%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  0/213 (0.00%)  0/354 (0.00%) 
Hypertension * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  1/354 (0.28%) 
Hypertensive Urgency * 1  0/133 (0.00%)  0/51 (0.00%)  0/132 (0.00%)  0/29 (0.00%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  0/285 (0.00%)  0/476 (0.00%)  0/151 (0.00%)  1/213 (0.47%)  0/354 (0.00%) 
1
Term from vocabulary, MedDRA Version 22.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ustekinumab Induction Responders(USTIRsp) Placebo Maintenance UST -I-Rsp -PBO Maintenance -UST-90mg SC Q8W- Maintenance UST-I-Rsp-UST 90 mg SC Every 12 Weeks (Q12W) Maintenance UST-I-Rsp-UST 90 mg SC Q12W/Q8W Maintenance UST-I-Rsp-UST 90 mg SC Q8W Maintenance UST IV-I-Rsp-UST-90mg Maintenance-UST-90mg SC Q8W Maintenance Placebo (PBO)-I-Rsp PBO Maintenance PBO-I-nonRsp- UST-130mg Intravenous/90mg SC Q12W Maintenance UST IV-I-nonRsp - UST-90 mg SC Q8W Maintenance Placebo Long Term Extension (LTE) UST 90 mg SC Q12W LTE UST 90 mg SC Q8W LTE
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   94/133 (70.68%)   34/51 (66.67%)   88/132 (66.67%)   20/29 (68.97%)   84/131 (64.12%)   18/29 (62.07%)   82/123 (66.67%)   160/285 (56.14%)   275/476 (57.77%)   83/151 (54.97%)   162/213 (76.06%)   293/354 (82.77%) 
Blood and lymphatic system disorders                         
Anaemia * 1  0/133 (0.00%)  0/51 (0.00%)  5/132 (3.79%)  1/29 (3.45%)  3/131 (2.29%)  0/29 (0.00%)  5/123 (4.07%)  6/285 (2.11%)  11/476 (2.31%)  2/151 (1.32%)  15/213 (7.04%)  17/354 (4.80%) 
Gastrointestinal disorders                         
Abdominal Pain * 1  17/133 (12.78%)  3/51 (5.88%)  12/132 (9.09%)  5/29 (17.24%)  11/131 (8.40%)  1/29 (3.45%)  15/123 (12.20%)  23/285 (8.07%)  38/476 (7.98%)  16/151 (10.60%)  38/213 (17.84%)  68/354 (19.21%) 
Abdominal Pain Upper * 1  3/133 (2.26%)  1/51 (1.96%)  4/132 (3.03%)  1/29 (3.45%)  2/131 (1.53%)  2/29 (6.90%)  5/123 (4.07%)  8/285 (2.81%)  15/476 (3.15%)  8/151 (5.30%)  11/213 (5.16%)  22/354 (6.21%) 
Constipation * 1  4/133 (3.01%)  1/51 (1.96%)  6/132 (4.55%)  2/29 (6.90%)  3/131 (2.29%)  0/29 (0.00%)  0/123 (0.00%)  6/285 (2.11%)  10/476 (2.10%)  0/151 (0.00%)  9/213 (4.23%)  22/354 (6.21%) 
Crohn's Disease * 1  12/133 (9.02%)  5/51 (9.80%)  12/132 (9.09%)  3/29 (10.34%)  12/131 (9.16%)  2/29 (6.90%)  13/123 (10.57%)  17/285 (5.96%)  40/476 (8.40%)  25/151 (16.56%)  44/213 (20.66%)  80/354 (22.60%) 
Diarrhoea * 1  7/133 (5.26%)  2/51 (3.92%)  11/132 (8.33%)  1/29 (3.45%)  5/131 (3.82%)  0/29 (0.00%)  11/123 (8.94%)  10/285 (3.51%)  12/476 (2.52%)  11/151 (7.28%)  30/213 (14.08%)  50/354 (14.12%) 
Gastrooesophageal Reflux Disease * 1  2/133 (1.50%)  2/51 (3.92%)  1/132 (0.76%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  2/123 (1.63%)  4/285 (1.40%)  7/476 (1.47%)  2/151 (1.32%)  11/213 (5.16%)  15/354 (4.24%) 
Nausea * 1  9/133 (6.77%)  3/51 (5.88%)  10/132 (7.58%)  3/29 (10.34%)  4/131 (3.05%)  1/29 (3.45%)  12/123 (9.76%)  15/285 (5.26%)  46/476 (9.66%)  12/151 (7.95%)  23/213 (10.80%)  34/354 (9.60%) 
Vomiting * 1  9/133 (6.77%)  3/51 (5.88%)  5/132 (3.79%)  2/29 (6.90%)  4/131 (3.05%)  2/29 (6.90%)  5/123 (4.07%)  6/285 (2.11%)  33/476 (6.93%)  2/151 (1.32%)  14/213 (6.57%)  26/354 (7.34%) 
General disorders                         
Fatigue * 1  6/133 (4.51%)  2/51 (3.92%)  8/132 (6.06%)  1/29 (3.45%)  6/131 (4.58%)  0/29 (0.00%)  9/123 (7.32%)  11/285 (3.86%)  15/476 (3.15%)  8/151 (5.30%)  13/213 (6.10%)  29/354 (8.19%) 
Injection Site Erythema * 1  0/133 (0.00%)  1/51 (1.96%)  1/132 (0.76%)  1/29 (3.45%)  7/131 (5.34%)  1/29 (3.45%)  2/123 (1.63%)  5/285 (1.75%)  7/476 (1.47%)  1/151 (0.66%)  7/213 (3.29%)  7/354 (1.98%) 
Pyrexia * 1  11/133 (8.27%)  2/51 (3.92%)  11/132 (8.33%)  3/29 (10.34%)  9/131 (6.87%)  1/29 (3.45%)  12/123 (9.76%)  16/285 (5.61%)  25/476 (5.25%)  9/151 (5.96%)  19/213 (8.92%)  19/354 (5.37%) 
Infections and infestations                         
Bronchitis * 1  4/133 (3.01%)  3/51 (5.88%)  1/132 (0.76%)  0/29 (0.00%)  6/131 (4.58%)  0/29 (0.00%)  3/123 (2.44%)  5/285 (1.75%)  7/476 (1.47%)  4/151 (2.65%)  13/213 (6.10%)  30/354 (8.47%) 
Gastroenteritis * 1  5/133 (3.76%)  1/51 (1.96%)  3/132 (2.27%)  0/29 (0.00%)  4/131 (3.05%)  0/29 (0.00%)  4/123 (3.25%)  8/285 (2.81%)  18/476 (3.78%)  7/151 (4.64%)  21/213 (9.86%)  41/354 (11.58%) 
Gastroenteritis Viral * 1  1/133 (0.75%)  3/51 (5.88%)  4/132 (3.03%)  0/29 (0.00%)  4/131 (3.05%)  2/29 (6.90%)  5/123 (4.07%)  6/285 (2.11%)  6/476 (1.26%)  2/151 (1.32%)  11/213 (5.16%)  12/354 (3.39%) 
Influenza * 1  4/133 (3.01%)  1/51 (1.96%)  8/132 (6.06%)  1/29 (3.45%)  5/131 (3.82%)  1/29 (3.45%)  4/123 (3.25%)  9/285 (3.16%)  8/476 (1.68%)  4/151 (2.65%)  25/213 (11.74%)  37/354 (10.45%) 
Nasopharyngitis * 1  10/133 (7.52%)  4/51 (7.84%)  17/132 (12.88%)  4/29 (13.79%)  14/131 (10.69%)  0/29 (0.00%)  15/123 (12.20%)  32/285 (11.23%)  52/476 (10.92%)  16/151 (10.60%)  54/213 (25.35%)  100/354 (28.25%) 
Pharyngitis Streptococcal * 1  2/133 (1.50%)  0/51 (0.00%)  0/132 (0.00%)  1/29 (3.45%)  0/131 (0.00%)  2/29 (6.90%)  2/123 (1.63%)  3/285 (1.05%)  1/476 (0.21%)  0/151 (0.00%)  2/213 (0.94%)  3/354 (0.85%) 
Sinusitis * 1  2/133 (1.50%)  0/51 (0.00%)  6/132 (4.55%)  2/29 (6.90%)  4/131 (3.05%)  2/29 (6.90%)  5/123 (4.07%)  12/285 (4.21%)  17/476 (3.57%)  8/151 (5.30%)  19/213 (8.92%)  36/354 (10.17%) 
Upper Respiratory Tract Infection * 1  21/133 (15.79%)  1/51 (1.96%)  9/132 (6.82%)  0/29 (0.00%)  13/131 (9.92%)  1/29 (3.45%)  7/123 (5.69%)  25/285 (8.77%)  33/476 (6.93%)  14/151 (9.27%)  40/213 (18.78%)  62/354 (17.51%) 
Urinary Tract Infection * 1  3/133 (2.26%)  1/51 (1.96%)  9/132 (6.82%)  1/29 (3.45%)  4/131 (3.05%)  1/29 (3.45%)  7/123 (5.69%)  5/285 (1.75%)  17/476 (3.57%)  7/151 (4.64%)  15/213 (7.04%)  35/354 (9.89%) 
Injury, poisoning and procedural complications                         
Contusion * 1  1/133 (0.75%)  1/51 (1.96%)  1/132 (0.76%)  2/29 (6.90%)  1/131 (0.76%)  0/29 (0.00%)  2/123 (1.63%)  1/285 (0.35%)  5/476 (1.05%)  5/151 (3.31%)  5/213 (2.35%)  5/354 (1.41%) 
Musculoskeletal and connective tissue disorders                         
Arthralgia * 1  18/133 (13.53%)  6/51 (11.76%)  22/132 (16.67%)  5/29 (17.24%)  18/131 (13.74%)  3/29 (10.34%)  23/123 (18.70%)  29/285 (10.18%)  49/476 (10.29%)  11/151 (7.28%)  27/213 (12.68%)  40/354 (11.30%) 
Arthritis * 1  3/133 (2.26%)  0/51 (0.00%)  3/132 (2.27%)  0/29 (0.00%)  1/131 (0.76%)  0/29 (0.00%)  8/123 (6.50%)  7/285 (2.46%)  3/476 (0.63%)  1/151 (0.66%)  1/213 (0.47%)  4/354 (1.13%) 
Back Pain * 1  6/133 (4.51%)  2/51 (3.92%)  5/132 (3.79%)  1/29 (3.45%)  6/131 (4.58%)  3/29 (10.34%)  2/123 (1.63%)  12/285 (4.21%)  15/476 (3.15%)  13/151 (8.61%)  18/213 (8.45%)  48/354 (13.56%) 
Pain in Extremity * 1  0/133 (0.00%)  1/51 (1.96%)  0/132 (0.00%)  1/29 (3.45%)  5/131 (3.82%)  1/29 (3.45%)  0/123 (0.00%)  4/285 (1.40%)  6/476 (1.26%)  1/151 (0.66%)  9/213 (4.23%)  18/354 (5.08%) 
Nervous system disorders                         
Headache * 1  15/133 (11.28%)  6/51 (11.76%)  15/132 (11.36%)  2/29 (6.90%)  15/131 (11.45%)  2/29 (6.90%)  16/123 (13.01%)  21/285 (7.37%)  41/476 (8.61%)  12/151 (7.95%)  19/213 (8.92%)  40/354 (11.30%) 
Psychiatric disorders                         
Anxiety * 1  1/133 (0.75%)  1/51 (1.96%)  2/132 (1.52%)  2/29 (6.90%)  0/131 (0.00%)  0/29 (0.00%)  0/123 (0.00%)  4/285 (1.40%)  3/476 (0.63%)  1/151 (0.66%)  6/213 (2.82%)  12/354 (3.39%) 
Respiratory, thoracic and mediastinal disorders                         
Cough * 1  3/133 (2.26%)  1/51 (1.96%)  4/132 (3.03%)  0/29 (0.00%)  7/131 (5.34%)  0/29 (0.00%)  6/123 (4.88%)  9/285 (3.16%)  26/476 (5.46%)  8/151 (5.30%)  13/213 (6.10%)  24/354 (6.78%) 
Oropharyngeal Pain * 1  4/133 (3.01%)  2/51 (3.92%)  2/132 (1.52%)  2/29 (6.90%)  3/131 (2.29%)  1/29 (3.45%)  2/123 (1.63%)  8/285 (2.81%)  13/476 (2.73%)  0/151 (0.00%)  10/213 (4.69%)  12/354 (3.39%) 
Skin and subcutaneous tissue disorders                         
Acne * 1  1/133 (0.75%)  3/51 (5.88%)  1/132 (0.76%)  0/29 (0.00%)  2/131 (1.53%)  1/29 (3.45%)  0/123 (0.00%)  5/285 (1.75%)  7/476 (1.47%)  2/151 (1.32%)  6/213 (2.82%)  9/354 (2.54%) 
Rash * 1  5/133 (3.76%)  2/51 (3.92%)  4/132 (3.03%)  1/29 (3.45%)  7/131 (5.34%)  2/29 (6.90%)  5/123 (4.07%)  5/285 (1.75%)  22/476 (4.62%)  5/151 (3.31%)  12/213 (5.63%)  20/354 (5.65%) 
Urt