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Study of Oral cMET Inhibitor INC280 in Patients With EGFR Wild-type (wt), Advanced Non-small Cell Lung Cancer (NSCLC) (Geometry Mono-1)

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: NCT02414139
Recruitment Status : Completed
First Posted : April 10, 2015
Results First Posted : March 20, 2024
Last Update Posted : March 20, 2024
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Carcinoma, Non-Small-Cell Lung
Intervention Drug: Capmatinib
Enrollment 373
Recruitment Details Participants were enrolled in 95 centers across 20 countries
Pre-assignment Details Screening assessments were conducted up to 28 days prior to the start of study treatment
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L) Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L) Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L) Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L) Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L) Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L) Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a) Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4) Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
Period Title: Treatment Period
Started 69 42 54 30 69 15 28 3 31 32
Completed 0 0 0 0 0 0 0 0 0 0
Not Completed 69 42 54 30 69 15 28 3 31 32
Reason Not Completed
Adverse Event             11             6             8             5             14             3             6             1             6             8
Death             0             0             1             1             0             0             0             0             0             1
Physician Decision             5             4             6             1             4             0             2             0             1             4
Progressive disease             48             31             37             21             43             12             16             2             20             14
Protocol deviation             0             0             1             0             0             0             0             0             0             0
Subject/Guardian decision             5             1             1             2             5             0             2             0             1             1
Study terminated (as per protocol) by Sponsor             0             0             0             0             3             0             2             0             3             4
Period Title: Post-treatment Efficacy Follow-up
Started 16 11 16 8 23 5 6 1 3 8
Completed 0 0 0 0 0 0 0 0 0 0
Not Completed 16 11 16 8 23 5 6 1 3 8
Reason Not Completed
Adverse Event             1             0             0             0             2             0             0             0             0             0
Death             0             1             0             0             1             0             0             0             0             1
Lost to Follow-up             1             0             0             0             0             0             0             0             0             0
Physician Decision             4             2             4             2             4             0             1             0             0             1
Progressive disease             6             5             9             5             15             4             5             1             3             3
Study terminated by sponsor             0             1             0             0             0             0             0             0             0             1
Subject/guardian decision             4             2             3             1             1             1             0             0             0             2
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Total
Hide Arm/Group Description Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L) Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L) Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L) Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L) Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L) Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L) Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a) Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4) Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b) Total of all reporting groups
Overall Number of Baseline Participants 69 42 54 30 69 15 28 3 31 32 373
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 69 participants 42 participants 54 participants 30 participants 69 participants 15 participants 28 participants 3 participants 31 participants 32 participants 373 participants
60.9  (9.56) 59.5  (9.11) 61.7  (10.00) 61.7  (9.23) 71.0  (8.32) 68.2  (10.36) 72.4  (7.02) 60.7  (10.69) 69.0  (6.29) 73.3  (8.35) 65.7  (10.18)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 42 participants 54 participants 30 participants 69 participants 15 participants 28 participants 3 participants 31 participants 32 participants 373 participants
Female
15
  21.7%
21
  50.0%
15
  27.8%
11
  36.7%
40
  58.0%
4
  26.7%
18
  64.3%
1
  33.3%
16
  51.6%
23
  71.9%
164
  44.0%
Male
54
  78.3%
21
  50.0%
39
  72.2%
19
  63.3%
29
  42.0%
11
  73.3%
10
  35.7%
2
  66.7%
15
  48.4%
9
  28.1%
209
  56.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants 42 participants 54 participants 30 participants 69 participants 15 participants 28 participants 3 participants 31 participants 32 participants 373 participants
Asian
17
  24.6%
4
   9.5%
14
  25.9%
11
  36.7%
19
  27.5%
6
  40.0%
4
  14.3%
1
  33.3%
5
  16.1%
3
   9.4%
84
  22.5%
Black
1
   1.4%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.2%
1
   3.1%
3
   0.8%
Caucasian
51
  73.9%
38
  90.5%
40
  74.1%
19
  63.3%
49
  71.0%
9
  60.0%
24
  85.7%
1
  33.3%
24
  77.4%
26
  81.3%
281
  75.3%
Native American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.4%
0
   0.0%
0
   0.0%
0
   0.0%
1
   3.2%
0
   0.0%
2
   0.5%
Unknown
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
1
  33.3%
0
   0.0%
0
   0.0%
1
   0.3%
Other
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
2
   6.3%
2
   0.5%
1.Primary Outcome
Title Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) Assessment
Hide Description

Percentage of participants with a best overall response defined as confirmed complete response (CR) or partial response (PR) by BIRC assessment per RECIST 1.1.

CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set (FAS)-including all subjects who received at least one dose of capmatinib
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 69 42 54 30 69 15 28 3 31 32 100 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of Participants
29.0
(18.7 to 41.2)
11.9
(4.0 to 25.6)
9.3
(3.1 to 20.3)
6.7
(0.8 to 22.1)
40.6
(28.9 to 53.1)
40.0
(16.3 to 67.7)
67.9
(47.6 to 84.1)
0.0
(0.0 to 70.8)
51.6
(33.1 to 69.8)
68.8
(50.0 to 83.9)
44.0
(34.1 to 54.3)
68.3
(55.0 to 79.7)
2.Secondary Outcome
Title Duration of Response (DOR) by BIRC Assessment
Hide Description

Time from the date of the first documented CR or PR by BIRC per RECIST 1.1 to the first documented progression or date of death due to any cause for patients with confirmed PR or CR. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals was reported. If a subject did not have an event, DOR was censored at the date of last adequate tumor assessment.

CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm.

PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with confirmed CR or PR by BIRC in FAS
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 20 5 5 2 28 6 19 0 16 22 44 41
Median (95% Confidence Interval)
Unit of Measure: Months
8.31
(4.17 to 15.44)
24.94
(2.69 to 24.94)
9.66 [1] 
(4.17 to NA)
4.19
(4.17 to 4.21)
9.72
(5.55 to 12.98)
7.54
(2.56 to 14.26)
12.58
(5.55 to 38.67)
9.05
(4.17 to 27.60)
16.59 [1] 
(8.34 to NA)
9.72
(5.62 to 12.98)
16.59
(8.41 to 22.11)
[1]
NA: not estimable due to the insufficient number of participants with events
3.Secondary Outcome
Title ORR by Investigator Assessment
Hide Description

Percentage of patients with a best overall response defined as confirmed CR or PR per RECIST 1.1 by investigator assessment.

CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm.

PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, including all subjects who received at least one dose of capmatinib.
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 69 42 54 30 69 15 28 3 31 32 100 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
27.5
(17.5 to 39.6)
7.1
(1.5 to 19.5)
9.3
(3.1 to 20.3)
3.3
(0.1 to 17.2)
43.5
(31.6 to 56.0)
40.0
(16.3 to 67.7)
60.7
(40.6 to 78.5)
0.0
(0.0 to 70.8)
45.2
(27.3 to 64.0)
56.3
(37.7 to 73.6)
44.0
(34.1 to 54.3)
58.3
(44.9 to 70.9)
4.Secondary Outcome
Title DOR by Investigator Assessment
Hide Description

Time from the date of the first documented CR or PR per RECIST 1.1 by investigator assessment to the first documented progression or death due to any cause for patients with confirmed PR or CR. The Kaplan-Meier method was used to estimate DOR, and the median DOR, along with 95% confidence intervals was reported. If a subject did not have an event, DOR was censored at the date of last adequate tumor assessment.

CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm.

PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with confirmed CR or PR by investigator assessment in FAS.
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 19 3 5 1 30 6 17 0 14 18 44 35
Median (95% Confidence Interval)
Unit of Measure: Months
6.80
(4.21 to 20.73)
6.93
(5.75 to 8.34)
19.48 [1] 
(2.83 to NA)
6.93 [1] 
(NA to NA)
8.31
(4.34 to 12.06)
9.66
(4.01 to 17.08)
13.83
(4.27 to 25.33)
14.57
(4.17 to 27.60)
15.21
(6.77 to 31.77)
8.38
(5.55 to 13.80)
13.96
(9.33 to 22.18)
[1]
NA: not estimable due to the insufficient number of participants with events
5.Secondary Outcome
Title Time to Response (TTR) by BIRC Assessment
Hide Description

Time between date of start of treatment until first documented response (confirmed CR or PR) per RECIST 1.1 by BIRC assessment.

CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm.

PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with confirmed CR or PR by BIRC in FAS
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 20 5 5 2 28 6 19 0 16 22 44 41
Median (Full Range)
Unit of Measure: Months
1.4
(0.5 to 6.8)
2.8
(1.4 to 16.6)
1.4
(1.2 to 6.2)
3.4
(1.3 to 5.5)
1.4
(1.2 to 5.6)
1.4
(1.2 to 2.9)
1.4
(1.3 to 6.9)
1.4
(1.1 to 9.8)
1.4
(1.2 to 7.2)
1.4
(1.1 to 9.8)
1.4
(1.2 to 7.2)
6.Secondary Outcome
Title TTR by Investigator Assessment
Hide Description

Time between date of start of treatment until first documented response (confirmed CR or PR) per RECIST 1.1 by investigator assessment.

CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm.

PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with confirmed CR or PR by investigator assessment in FAS
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 19 3 5 1 30 6 17 0 14 18 44 35
Median (Full Range)
Unit of Measure: Months
1.4
(1.2 to 5.4)
1.4
(1.3 to 1.4)
1.3
(1.2 to 1.7)
1.3
(1.3 to 1.3)
1.4
(1.2 to 11.1)
1.4
(1.3 to 2.5)
1.4
(1.2 to 4.0)
1.4
(1.1 to 12.3)
1.4
(1.2 to 5.6)
1.4
(1.1 to 12.3)
1.4
(1.2 to 5.6)
7.Secondary Outcome
Title Disease Control Rate (DCR)
Hide Description

Percentage of participants with a best overall response of confirmed CR, PR or stable disease (SD) per RECIST 1.1 by BIRC and investigator assessment.

CR: Disappearance of all non-nodal target and non-target lesions. In addition, any pathological lymph nodes assigned as target and non-target lesions must have a reduction in short axis to < 10 mm.

PR: At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

SD: Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progressive disease.
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, including all subjects who received at least one dose of capmatinib.
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 69 42 54 30 69 15 28 3 31 32 100 60
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
By BIRC assessment
71.0
(58.8 to 81.3)
54.8
(38.7 to 70.2)
46.3
(32.6 to 60.4)
53.3
(34.3 to 71.7)
78.3
(66.7 to 87.3)
66.7
(38.4 to 88.2)
96.4
(81.7 to 99.9)
100.0
(29.2 to 100.0)
90.3
(74.2 to 98.0)
100.0
(89.1 to 100.0)
82.0
(73.1 to 89.0)
98.3
(91.1 to 100.0)
By investigator assessment
60.9
(48.4 to 72.4)
45.2
(29.8 to 61.3)
44.4
(30.9 to 58.6)
46.7
(28.3 to 65.7)
76.8
(65.1 to 86.1)
73.3
(44.9 to 92.2)
96.4
(81.7 to 99.9)
100.0
(29.2 to 100.0)
90.3
(74.2 to 98.0)
96.9
(83.8 to 99.9)
81.0
(71.9 to 88.2)
96.7
(88.5 to 99.6)
8.Secondary Outcome
Title Progression-Free Survival
Hide Description

Time from start of treatment to the date of the first documented progression or death due to any cause per RECIST 1.1 by BIRC and investigator assessment. Clinical deterioration was not considered as a qualifying event for progression. PFS was censored at the last adequate tumor assessment if one of the following occurred: absence of event or the event occurred after two or more missing tumor assessments.

The Kaplan-Meier method was used to estimate PFS, and the median PFS, along with 95% confidence intervals, was reported.

Progressive disease: For target lesions, at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm^2. For non-target lesions, unequivocal progression of existing non-target lesions
Time Frame Up to approximately 5 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, including all subjects who received at least one dose of capmatinib.
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 69 42 54 30 69 15 28 3 31 32 100 60
Median (95% Confidence Interval)
Unit of Measure: Months
By BIRC assessment
4.07
(2.86 to 4.83)
2.66
(1.41 to 3.09)
2.66
(1.41 to 4.14)
3.55
(2.20 to 4.21)
5.42
(4.17 to 6.97)
4.17
(1.45 to 6.87)
12.42
(8.21 to 23.39)
2.79
(2.07 to 4.24)
6.93
(4.17 to 13.34)
12.45
(6.87 to 22.05)
5.49
(4.17 to 8.11)
12.45
(8.31 to 17.97)
By investigator assessment
4.14
(2.79 to 5.52)
2.40
(1.45 to 2.83)
2.60
(1.48 to 3.09)
2.73
(1.45 to 3.78)
4.80
(4.11 to 7.75)
2.76
(1.45 to 6.87)
11.99
(5.52 to 16.92)
2.76
(2.07 to 2.79)
6.90
(5.55 to 17.31)
9.79
(5.75 to 16.36)
6.60
(4.70 to 8.18)
11.07
(6.87 to 15.18)
9.Secondary Outcome
Title Overall Survival (OS)
Hide Description

Time from start of treatment to the date of death due to any cause. If the patient was alive at the date of the analysis cut-off or lost to follow-up, then OS was censored at the last contact date prior to data cut-off date.

The Kaplan-Meier method was used to estimate OS, and the median OS, along with 95% confidence intervals, was reported.
Time Frame Up to approximately 6 years
Hide Outcome Measure Data
Hide Analysis Population Description
FAS, including all subjects who received at least one dose of capmatinib.
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L)
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
Overall Number of Participants Analyzed 69 42 54 30 69 15 28 3 31 32 100 60
Median (95% Confidence Interval)
Unit of Measure: Months
10.61
(6.28 to 17.22)
7.46
(5.59 to 10.18)
10.15
(5.52 to 15.74)
9.46
(4.11 to 12.32)
13.57
(8.61 to 22.24)
9.56 [1] 
(4.80 to NA)
20.76
(12.42 to 43.93)
4.14 [1] 
(2.07 to NA)
25.95
(13.54 to 43.40)
21.36
(12.85 to 34.76)
16.79
(11.63 to 23.82)
21.36
(15.24 to 30.52)
[1]
NA: not estimable due to the insufficient number of participants with events
10.Secondary Outcome
Title Pharmacokinetic (PK) Concentrations of Capmatinib
Hide Description

PK concentrations of capmatinib. Plasma concentrations of capmatinib were measured using validated liquid chromatography-tandem mass spectrometry (LCMS/MS) methods with a lower limit of quantification (LLOQ) of approximately 1.0 ng/mL.

Capmatinib concentration data was summarized for Cohorts 1a, 1b, 2, 3, 4, 5a and 5b when capmatinib was administered in fasted state; and for Cohorts 6 and 7 when capmatinib was administered with or without food.
Time Frame Cycle (C) 1 Day (D) 1 predose and 2 hours post-dose, C1D15 pre-dose and 2 hours post-dose, C3D1 pre-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who received at least one dose of capmatinib and provided at least one evaluable pharmacokinetic concentration for capmatinib at the specified time points. Participants who received capmatinib under the same administration conditions (fasted state or with/without food) were pooled together.
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State Cohorts 6-7: Capmatinib Administration With ot Without Food
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Participants from Cohorts 6 and 7 who received capmatinib with or without food
Overall Number of Participants Analyzed 275 54
Mean (Standard Deviation)
Unit of Measure: nanogram/mililiter (ng/ml)
Cycle 1 Day 1- pre-dose Number Analyzed 275 participants 54 participants
0.00  (0.00) 0.00  (0.00)
Cycle 1 Day 1- 2 hours post-dose Number Analyzed 275 participants 53 participants
3360  (1920) 3060  (1780)
Cycle 1 Day 15 - pre-dose Number Analyzed 176 participants 29 participants
727  (781) 663  (806)
Cycle 1 Day 15- 2 hours post-dose Number Analyzed 209 participants 47 participants
4100  (2100) 4340  (2000)
Cycle 3 Day 1 - pre-dose Number Analyzed 96 participants 18 participants
687  (1000) 672  (745)
11.Secondary Outcome
Title Maximum Concentration (Cmax) of Capmatinib
Hide Description

Cmax of capmatinib was estimated by non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL.

Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time Frame Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (Cmax for capmatinib) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Overall Number of Participants Analyzed 55
Mean (Standard Deviation)
Unit of Measure: ng/ml
Cycle 1 Day 1 Number Analyzed 55 participants
4230  (2290)
Cycle 1 Day 15 Number Analyzed 44 participants
5450  (2560)
12.Secondary Outcome
Title Maximum Concentration (Cmax) of CMN288
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Cmax of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. Cmax is the maximum plasma drug concentration after single dose administration. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL.

Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time Frame Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (Cmax for CMN288) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Overall Number of Participants Analyzed 51
Mean (Standard Deviation)
Unit of Measure: ng/ml
Cycle 1 Day 1 Number Analyzed 51 participants
1910  (1420)
Cycle 1 Day 15 Number Analyzed 42 participants
1420  (725)
13.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Zero to Time Infinity (AUCinf) of Capmatinib
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AUCinf of capmatinib was estimated by non-compartmental analysis. AUCinf is the area under the plasma concentration-time curve extrapolated to infinity. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL.

Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time Frame Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (AUCinf for capmatinib) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Overall Number of Participants Analyzed 44
Mean (Standard Deviation)
Unit of Measure: nanogram * hour / mililiter (ng*h/ml)
17000  (7770)
14.Secondary Outcome
Title Area Under the Plasma Concentration-time Curve From Zero to Time Infinity (AUCinf) of CMN288
Hide Description

AUCinf of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. AUCinf is the area under the plasma concentration-time curve extrapolated to infinity. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL.

Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time Frame Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (AUCinf for CMN288) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Overall Number of Participants Analyzed 27
Mean (Standard Deviation)
Unit of Measure: ng*h/ml
9020  (5060)
15.Secondary Outcome
Title Time to Reach Maximum Concentration (Tmax) of Capmatinib
Hide Description

Tmax of capmatinib was estimated by non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL.

Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time Frame Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (Tmax for capmatinib) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Overall Number of Participants Analyzed 55
Median (Full Range)
Unit of Measure: hour
Cycle 1 Day 1 Number Analyzed 55 participants
1.87
(0.583 to 4.03)
Cycle 1 Day 15 Number Analyzed 44 participants
1.09
(0.5 to 6.07)
16.Secondary Outcome
Title Time to Reach Maximum Concentration (Tmax) of CMN288
Hide Description

Tmax of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. Tmax is the time to reach maximum plasma concentration. Actual recorded sampling times were considered for the calculations. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL.

Only a subset of participants from cohorts 1-5, who had an extensive PK collection schedule, were included in this analysis
Time Frame Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (Tmax for CMN288) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Overall Number of Participants Analyzed 51
Median (Full Range)
Unit of Measure: hour
Cycle 1 Day 1 Number Analyzed 51 participants
1.93
(0.950 to 4.03)
Cycle 1 Day 15 Number Analyzed 42 participants
1.91
(0.883 to 7.98)
17.Secondary Outcome
Title Elimination Half-life (T1/2) of Capmatinib
Hide Description

T1/2 of capmatinib was estimated by non-compartmental analysis. T1/2 is the time it takes for the concentration of capmatinib in the bloodstream to decrease by half. Plasma concentrations of capmatinib were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL.

Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time Frame Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (T1/2 for capmatinib) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Overall Number of Participants Analyzed 47
Mean (Standard Deviation)
Unit of Measure: hour
Cycle 1 Day 1 Number Analyzed 47 participants
1.87  (0.947)
Cycle 1 Day 15 Number Analyzed 37 participants
2.40  (0.652)
18.Secondary Outcome
Title Elimination Half-life (T1/2) of CMN288
Hide Description

T1/2 of CMN288 (metabolite of capmatinib) was estimated by non-compartmental analysis. T1/2 is the time it takes for the concentration of CMN288 in the bloodstream to decrease by half. Plasma concentrations of metabolite CMN288 were measured using validated LCMS/MS methods with a LLOQ of approximately 1.0 ng/mL.

Only a subset of participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b, who had an extensive PK collection schedule, were included in this analysis
Time Frame Cycle 1 Day 1 and Day 15 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days
Hide Outcome Measure Data
Hide Analysis Population Description
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received at least one dose of capmatinib with extensive PK sampling collection and an evaluable PK parameter (T1/2 for CMN288) at the specified time points. Participants received capmatinib under the same administration conditions (fasted state) and were pooled together for analysis
Arm/Group Title Cohorts 1-5: Capmatinib Administration in Fasted State
Hide Arm/Group Description:
Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: hour
Cycle 1 Day 1 Number Analyzed 40 participants
3.14  (1.42)
Cycle 1 Day 15 Number Analyzed 34 participants
3.06  (0.949)
19.Post-Hoc Outcome
Title All Collected Deaths
Hide Description

On-treatment deaths were collected from start of treatment to 30 days after last dose of treatment.

Post-treatment efficacy/survival follow-up deaths were collected from 31 days after last dose of treatment until the end of the study.

All deaths refer to the sum of on-treatment and post-treatment efficacy/survival follow-up deaths.
Time Frame On-treatment: Up to approximately 5.5 years. Post-treatment efficacy/survival follow-up: Up to approximately 6 years
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Hide Analysis Population Description
FAS, including all subjects who received at least one dose of capmatinib
Arm/Group Title Cohort 1a: Pre-treated Patients With MET GCN ≥ 10 (2/3L) Cohort 1b: Pre-treated Patients With MET GCN ≥ 6 and < 10 (2/3L) Cohort 2: Pre-treated Patients With MET GCN ≥ 4 and < 6 (2/3L) Cohort 3: Pre-treated Patients With MET GCN < 4 (2/3L) Cohort 4: Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5a: Treatment-naïve Patients With MET GCN ≥10 (1L) Cohort 5b: Treatment-naïve Patients With MET Mutation Regardless of MET GCN (1L) Cohort 6.1 (Expansion of Cohort 1a): Pre-treated Patients MET GCN ≥ 10 Without MET Mutation (2L) Cohort 6.2 (Expansion of Cohort 4): Pre-treated Patients With MET Mutation (2L) Cohort 7 (Expansion of Cohort 5b): Treatment-naïve With MET Mutation Regardless of MET GCN (1L) Cohort 4 + Cohort 6.2: All Pre-treated Patients With MET Mutation Regardless of MET GCN (2/3L) Cohort 5b + Cohort 7: All Treatment-naive With MET Mutation Regardless of MET GCN (1L) All Participants
Hide Arm/Group Description:
Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)
Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)
Pre-treated patients with MET GCN ≥ 10 without MET mutation treated with INC280 at 400 mg BID as second line (2L) (expansion cohort of Cohort 1a)
Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as second line (2L)(expansion of Cohort 4)
Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L) (expansion cohort of Cohort 5b)
All pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L). (Participants from Cohort 4 and Cohort 6.2)
All treatment naive patients with MET mutation regardless of MET GCN treated with INC280 at 400 mg BID as first line (1L) (Participants from Cohort 5b and Cohort 7)
All participants
Overall Number of Participants Analyzed 69 42 54 30 69 15 28 3 31 32 100 60 373
Measure Type: Number
Unit of Measure: Participants
On-treatment Number Analyzed 69 participants 42 participants 54 participants 30 participants 69 participants 15 participants 28 participants 3 participants 31 participants 32 participants 100 participants 60 participants 373 participants
10 7 12 4 14 0 5 1 5 5 19 10 63
Post-treatment efficacy/survival follow-up Number Analyzed 59 participants 35 participants 42 participants 25 participants 55 participants 15 participants 20 participants 2 participants 20 participants 23 participants 75 participants 43 participants 296 participants
44 26 34 22 44 13 13 2 17 16 61 29 231
All deaths Number Analyzed 69 participants 42 participants 54 participants 30 participants 69 participants 15 participants 28 participants 3 participants 31 participants 32 participants 100 participants 60 participants 373 participants
54 33 46 26 58 13 18 3 22 21 80 39 294
Time Frame Adverse events (AEs) were collected from first dose of study treatment to 30 days after last dose of study medication (on-treatment), up to approximately 5.5 years. Deaths were collected in the post treatment efficacy/survival follow-up from 31 days after last dose of study medication until the end of the study, up to approximately 6 years.
Adverse Event Reporting Description Deaths in the post-treatment efficacy/survival follow-up are not counted as AEs. The total number at risk in the post-treatment efficacy/survival includes patients who entered the post-treatment efficacy and/or survival follow-up periods.
 
Arm/Group Title Cohort 1a: On-treatment Cohort 1b: On-treatment Cohort 2: On-treatment Cohort 3: On-treatment Cohort 4: On-treatment Cohort 5a: On-treatment Cohort 5b: On-treatment Cohort 6.1 (Expansion of Cohort 1a): On-treatment Cohort 6.2 (Expansion of Cohort 4): On-treatment Cohort 7 (Expansion of Cohort 5b): On-treatment Cohort 4 + Cohort 6.2: On-treatment Cohort 5b + Cohort 7: On-treatment All Patients: On-treatment Cohort 1a: Post-treatment Efficacy/Survival Follow-up Cohort 1b: Post-treatment Efficacy/Survival Follow-up Period Cohort 2: Post-treatment Efficacy/Survival Follow-up Period Cohort 3: Post-treatment Efficacy/Survival Follow-up Period Cohort 4: Post-treatment Efficacy/Survival Follow-up Period Cohort 5a: Post-treatment Efficacy/Survival Follow-up Period Cohort 5b: Post-treatment Efficacy/Survival Follow-up Period Cohort 6.1 (Expansion of Cohort 1a): Post-treatment Efficacy/Survival Follow-up Period Cohort 6.2 (Expansion of Cohort 4): Post-treatment Efficacy/Survival Follow-up Period Cohort 7 (Expansion of Cohort 5b): Post-treatment Efficacy/Survival Follow-up Period Cohort 4 + Cohort 6.2: Post-treatment Efficacy/Survival Follow-up Period Cohort 5b + Cohort 7: Post-treatment Efficacy/Survival Follow-up Period All Patients: Post-treatment Efficacy/Survival Follow-up
Hide Arm/Group Description AEs collected during the on-treatment period (up to 30 days post-treatment) AEs collected during the on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during on-treatment period (up to 30 days post-treatment) AEs collected during the on-treatment period (up to 30 days post-treatment) Deaths collected in the post- treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post- treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post-treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period Deaths collected in the post- treatment efficacy/survival follow-up period (starting from day 31 post- treatment). No AEs were collected during this period
All-Cause Mortality
Cohort 1a: On-treatment Cohort 1b: On-treatment Cohort 2: On-treatment Cohort 3: On-treatment Cohort 4: On-treatment Cohort 5a: On-treatment Cohort 5b: On-treatment Cohort 6.1 (Expansion of Cohort 1a): On-treatment Cohort 6.2 (Expansion of Cohort 4): On-treatment Cohort 7 (Expansion of Cohort 5b): On-treatment Cohort 4 + Cohort 6.2: On-treatment Cohort 5b + Cohort 7: On-treatment All Patients: On-treatment Cohort 1a: Post-treatment Efficacy/Survival Follow-up Cohort 1b: Post-treatment Efficacy/Survival Follow-up Period Cohort 2: Post-treatment Efficacy/Survival Follow-up Period Cohort 3: Post-treatment Efficacy/Survival Follow-up Period Cohort 4: Post-treatment Efficacy/Survival Follow-up Period Cohort 5a: Post-treatment Efficacy/Survival Follow-up Period Cohort 5b: Post-treatment Efficacy/Survival Follow-up Period Cohort 6.1 (Expansion of Cohort 1a): Post-treatment Efficacy/Survival Follow-up Period Cohort 6.2 (Expansion of Cohort 4): Post-treatment Efficacy/Survival Follow-up Period Cohort 7 (Expansion of Cohort 5b): Post-treatment Efficacy/Survival Follow-up Period Cohort 4 + Cohort 6.2: Post-treatment Efficacy/Survival Follow-up Period Cohort 5b + Cohort 7: Post-treatment Efficacy/Survival Follow-up Period All Patients: Post-treatment Efficacy/Survival Follow-up
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 (%) 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   10/69 (14.49%)   7/42 (16.67%)   12/54 (22.22%)   4/30 (13.33%)   14/69 (20.29%)   0/15 (0.00%)   5/28 (17.86%)   1/3 (33.33%)   5/31 (16.13%)   5/32 (15.63%)   19/100 (19.00%)   10/60 (16.67%)   63/373 (16.89%)   44/59 (74.58%)   26/35 (74.29%)   34/42 (80.95%)   22/25 (88.00%)   44/55 (80.00%)   13/15 (86.67%)   13/20 (65.00%)   2/2 (100.00%)   17/20 (85.00%)   16/23 (69.57%)   61/75 (81.33%)   29/43 (67.44%)   231/296 (78.04%) 
Hide Serious Adverse Events
Cohort 1a: On-treatment Cohort 1b: On-treatment Cohort 2: On-treatment Cohort 3: On-treatment Cohort 4: On-treatment Cohort 5a: On-treatment Cohort 5b: On-treatment Cohort 6.1 (Expansion of Cohort 1a): On-treatment Cohort 6.2 (Expansion of Cohort 4): On-treatment Cohort 7 (Expansion of Cohort 5b): On-treatment Cohort 4 + Cohort 6.2: On-treatment Cohort 5b + Cohort 7: On-treatment All Patients: On-treatment Cohort 1a: Post-treatment Efficacy/Survival Follow-up Cohort 1b: Post-treatment Efficacy/Survival Follow-up Period Cohort 2: Post-treatment Efficacy/Survival Follow-up Period Cohort 3: Post-treatment Efficacy/Survival Follow-up Period Cohort 4: Post-treatment Efficacy/Survival Follow-up Period Cohort 5a: Post-treatment Efficacy/Survival Follow-up Period Cohort 5b: Post-treatment Efficacy/Survival Follow-up Period Cohort 6.1 (Expansion of Cohort 1a): Post-treatment Efficacy/Survival Follow-up Period Cohort 6.2 (Expansion of Cohort 4): Post-treatment Efficacy/Survival Follow-up Period Cohort 7 (Expansion of Cohort 5b): Post-treatment Efficacy/Survival Follow-up Period Cohort 4 + Cohort 6.2: Post-treatment Efficacy/Survival Follow-up Period Cohort 5b + Cohort 7: Post-treatment Efficacy/Survival Follow-up Period All Patients: Post-treatment Efficacy/Survival Follow-up
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 (%) 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   42/69 (60.87%)   21/42 (50.00%)   30/54 (55.56%)   15/30 (50.00%)   38/69 (55.07%)   9/15 (60.00%)   14/28 (50.00%)   2/3 (66.67%)   14/31 (45.16%)   17/32 (53.13%)   52/100 (52.00%)   31/60 (51.67%)   202/373 (54.16%)   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0 
Blood and lymphatic system disorders                                                     
Anaemia † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Febrile neutropenia † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Thrombocytopenia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  1/100 (1.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiac disorders                                                     
Atrial fibrillation † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiac arrest † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiac failure † 1  2/69 (2.90%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiopulmonary failure † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Coronary artery disease † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Myocardial infarction † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pericardial effusion † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Supraventricular tachycardia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Tachycardia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Congenital, familial and genetic disorders                                                     
Spinal muscular atrophy † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Ear and labyrinth disorders                                                     
Hypoacusis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Vertigo † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Endocrine disorders                                                     
Inappropriate antidiuretic hormone secretion † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Primary adrenal insufficiency † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Gastrointestinal disorders                                                     
Abdominal pain † 1  1/69 (1.45%)  2/42 (4.76%)  2/54 (3.70%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Abdominal pain upper † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Anal prolapse † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Ascites † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Constipation † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Diarrhoea † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Duodenal stenosis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Duodenitis † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dysphagia † 1  2/69 (2.90%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Intestinal obstruction † 1  1/69 (1.45%)  0/42 (0.00%)  2/54 (3.70%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Intestinal polyp † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Nausea † 1  3/69 (4.35%)  3/42 (7.14%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  7/373 (1.88%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Oesophageal stenosis † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pancreatitis acute † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Stomatitis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Vomiting † 1  4/69 (5.80%)  2/42 (4.76%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  1/100 (1.00%)  1/60 (1.67%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
General disorders                                                     
Asthenia † 1  3/69 (4.35%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Drug withdrawal syndrome † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Fatigue † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
General physical health deterioration † 1  3/69 (4.35%)  3/42 (7.14%)  2/54 (3.70%)  1/30 (3.33%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  1/100 (1.00%)  1/60 (1.67%)  11/373 (2.95%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Generalised oedema † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Malaise † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Non-cardiac chest pain † 1  2/69 (2.90%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Oedema peripheral † 1  2/69 (2.90%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  0/100 (0.00%)  3/60 (5.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pain † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Peripheral swelling † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  2/69 (2.90%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pyrexia † 1  2/69 (2.90%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Stenosis † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Vascular device occlusion † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hepatobiliary disorders                                                     
Drug-induced liver injury † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hepatic function abnormal † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hepatitis † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hepatotoxicity † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperbilirubinaemia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Infections and infestations                                                     
Bronchitis † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
COVID-19 † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
COVID-19 pneumonia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cellulitis † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  4/69 (5.80%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  4/100 (4.00%)  1/60 (1.67%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Device related infection † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Erysipelas † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  2/60 (3.33%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Haemophilus infection † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Herpes zoster † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Infection † 1  0/69 (0.00%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Infectious pleural effusion † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Influenza † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Lung abscess † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Medical device site infection † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pleural infection † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia † 1  7/69 (10.14%)  4/42 (9.52%)  3/54 (5.56%)  1/30 (3.33%)  4/69 (5.80%)  0/15 (0.00%)  0/28 (0.00%)  1/3 (33.33%)  2/31 (6.45%)  1/32 (3.13%)  6/100 (6.00%)  1/60 (1.67%)  23/373 (6.17%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia aspiration † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia bacterial † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia influenzal † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pyelonephritis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  2/69 (2.90%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Respiratory tract infection † 1  1/69 (1.45%)  0/42 (0.00%)  2/54 (3.70%)  2/30 (6.67%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Sepsis † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Septic shock † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Urinary tract infection † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  2/30 (6.67%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Urosepsis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Injury, poisoning and procedural complications                                                     
Accidental exposure to product † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Femur fracture † 1  1/69 (1.45%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Fracture displacement † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Lower limb fracture † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Radiation necrosis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Thoracic vertebral fracture † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Toxicity to various agents † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Investigations                                                     
Amylase increased † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Eastern Cooperative Oncology Group performance status worsened † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
General physical condition abnormal † 1  0/69 (0.00%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  1/3 (33.33%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Liver function test abnormal † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Platelet count decreased † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
SARS-CoV-2 test positive † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Troponin increased † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Metabolism and nutrition disorders                                                     
Decreased appetite † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dehydration † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  2/31 (6.45%)  1/32 (3.13%)  2/100 (2.00%)  1/60 (1.67%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperkalaemia † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypokalaemia † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hyponatraemia † 1  2/69 (2.90%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  2/60 (3.33%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal and connective tissue disorders                                                     
Arthralgia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  1/69 (1.45%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  1/100 (1.00%)  1/60 (1.67%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Back pain † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Bone pain † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Muscular weakness † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal chest pain † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Osteolysis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pain in extremity † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Sacroiliitis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                                                     
Adenocarcinoma gastric † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Breast cancer † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cancer pain † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Rectal cancer † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Squamous cell carcinoma of skin † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Tumour haemorrhage † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Tumour pain † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Nervous system disorders                                                     
Aphasia † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cerebral ischaemia † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cerebral mass effect † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cerebrovascular accident † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Epilepsy † 1  1/69 (1.45%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Headache † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hemiparesis † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Neurological symptom † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Paraplegia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Seizure † 1  2/69 (2.90%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Psychiatric disorders                                                     
Agitation † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Anxiety † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Confusional state † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Disorientation † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Mental status changes † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Organic brain syndrome † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Renal and urinary disorders                                                     
Acute kidney injury † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Calculus urinary † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Haematuria † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Renal failure † 1  1/69 (1.45%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Renal infarct † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Urinary retention † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Reproductive system and breast disorders                                                     
Breast pain † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Genital prolapse † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pelvic pain † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Scrotal oedema † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Respiratory, thoracic and mediastinal disorders                                                     
Acute respiratory failure † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Aspiration † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Asthma † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Chronic obstructive pulmonary disease † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cough † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dyspnoea † 1  6/69 (8.70%)  4/42 (9.52%)  3/54 (5.56%)  2/30 (6.67%)  6/69 (8.70%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  7/100 (7.00%)  3/60 (5.00%)  26/373 (6.97%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Haemoptysis † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Interstitial lung disease † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  1/60 (1.67%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Organising pneumonia † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pleural effusion † 1  6/69 (8.70%)  1/42 (2.38%)  3/54 (5.56%)  0/30 (0.00%)  2/69 (2.90%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  3/100 (3.00%)  2/60 (3.33%)  16/373 (4.29%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pleurisy † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pleuritic pain † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonitis † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  3/69 (4.35%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  3/100 (3.00%)  2/60 (3.33%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumothorax † 1  1/69 (1.45%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary embolism † 1  0/69 (0.00%)  3/42 (7.14%)  1/54 (1.85%)  2/30 (6.67%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  7/373 (1.88%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary haemorrhage † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary venous thrombosis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Respiratory distress † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Respiratory failure † 1  3/69 (4.35%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Skin and subcutaneous tissue disorders                                                     
Urticaria † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Vascular disorders                                                     
Embolism † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypertension † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypotension † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Jugular vein thrombosis † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Peripheral ischaemia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Superior vena cava syndrome † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Thrombosis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Venous thrombosis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
1
Term from vocabulary, MedDRA (26.0)
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1a: On-treatment Cohort 1b: On-treatment Cohort 2: On-treatment Cohort 3: On-treatment Cohort 4: On-treatment Cohort 5a: On-treatment Cohort 5b: On-treatment Cohort 6.1 (Expansion of Cohort 1a): On-treatment Cohort 6.2 (Expansion of Cohort 4): On-treatment Cohort 7 (Expansion of Cohort 5b): On-treatment Cohort 4 + Cohort 6.2: On-treatment Cohort 5b + Cohort 7: On-treatment All Patients: On-treatment Cohort 1a: Post-treatment Efficacy/Survival Follow-up Cohort 1b: Post-treatment Efficacy/Survival Follow-up Period Cohort 2: Post-treatment Efficacy/Survival Follow-up Period Cohort 3: Post-treatment Efficacy/Survival Follow-up Period Cohort 4: Post-treatment Efficacy/Survival Follow-up Period Cohort 5a: Post-treatment Efficacy/Survival Follow-up Period Cohort 5b: Post-treatment Efficacy/Survival Follow-up Period Cohort 6.1 (Expansion of Cohort 1a): Post-treatment Efficacy/Survival Follow-up Period Cohort 6.2 (Expansion of Cohort 4): Post-treatment Efficacy/Survival Follow-up Period Cohort 7 (Expansion of Cohort 5b): Post-treatment Efficacy/Survival Follow-up Period Cohort 4 + Cohort 6.2: Post-treatment Efficacy/Survival Follow-up Period Cohort 5b + Cohort 7: Post-treatment Efficacy/Survival Follow-up Period All Patients: Post-treatment Efficacy/Survival Follow-up
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 (%) 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 (%) Affected / at Risk (%) Affected / at Risk (%)
Total   66/69 (95.65%)   41/42 (97.62%)   53/54 (98.15%)   28/30 (93.33%)   66/69 (95.65%)   15/15 (100.00%)   28/28 (100.00%)   3/3 (100.00%)   29/31 (93.55%)   31/32 (96.88%)   95/100 (95.00%)   59/60 (98.33%)   360/373 (96.51%)   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0   0/0 
Blood and lymphatic system disorders                                                     
Anaemia † 1  5/69 (7.25%)  2/42 (4.76%)  5/54 (9.26%)  6/30 (20.00%)  8/69 (11.59%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  4/31 (12.90%)  2/32 (6.25%)  12/100 (12.00%)  4/60 (6.67%)  35/373 (9.38%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Leukopenia † 1  1/69 (1.45%)  0/42 (0.00%)  2/54 (3.70%)  1/30 (3.33%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Lymphopenia † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  2/30 (6.67%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Neutropenia † 1  2/69 (2.90%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  1/69 (1.45%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  2/100 (2.00%)  2/60 (3.33%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Thrombocytopenia † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  2/69 (2.90%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  3/31 (9.68%)  3/32 (9.38%)  5/100 (5.00%)  3/60 (5.00%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiac disorders                                                     
Atrial fibrillation † 1  2/69 (2.90%)  0/42 (0.00%)  2/54 (3.70%)  0/30 (0.00%)  2/69 (2.90%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  2/100 (2.00%)  1/60 (1.67%)  8/373 (2.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cardiac failure † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  0/100 (0.00%)  2/60 (3.33%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Palpitations † 1  1/69 (1.45%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  2/69 (2.90%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  2/100 (2.00%)  3/60 (5.00%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Sinus bradycardia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  4/69 (5.80%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  4/100 (4.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Tachycardia † 1  0/69 (0.00%)  3/42 (7.14%)  0/54 (0.00%)  0/30 (0.00%)  2/69 (2.90%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Ear and labyrinth disorders                                                     
Hypoacusis † 1  2/69 (2.90%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  3/69 (4.35%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  0/31 (0.00%)  5/32 (15.63%)  3/100 (3.00%)  7/60 (11.67%)  14/373 (3.75%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Tinnitus † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  3/28 (10.71%)  0/3 (0.00%)  3/31 (9.68%)  1/32 (3.13%)  3/100 (3.00%)  4/60 (6.67%)  8/373 (2.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Vertigo † 1  2/69 (2.90%)  2/42 (4.76%)  2/54 (3.70%)  2/30 (6.67%)  5/69 (7.25%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  6/100 (6.00%)  1/60 (1.67%)  15/373 (4.02%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Endocrine disorders                                                     
Hyperthyroidism † 1  1/69 (1.45%)  3/42 (7.14%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  1/100 (1.00%)  2/60 (3.33%)  7/373 (1.88%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Gastrointestinal disorders                                                     
Abdominal discomfort † 1  1/69 (1.45%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  2/69 (2.90%)  0/15 (0.00%)  0/28 (0.00%)  1/3 (33.33%)  0/31 (0.00%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Abdominal pain † 1  2/69 (2.90%)  3/42 (7.14%)  7/54 (12.96%)  1/30 (3.33%)  3/69 (4.35%)  0/15 (0.00%)  3/28 (10.71%)  0/3 (0.00%)  1/31 (3.23%)  3/32 (9.38%)  4/100 (4.00%)  6/60 (10.00%)  23/373 (6.17%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Abdominal pain upper † 1  4/69 (5.80%)  4/42 (9.52%)  2/54 (3.70%)  2/30 (6.67%)  5/69 (7.25%)  0/15 (0.00%)  5/28 (17.86%)  0/3 (0.00%)  2/31 (6.45%)  3/32 (9.38%)  7/100 (7.00%)  8/60 (13.33%)  27/373 (7.24%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Abnormal faeces † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Constipation † 1  16/69 (23.19%)  9/42 (21.43%)  10/54 (18.52%)  7/30 (23.33%)  9/69 (13.04%)  6/15 (40.00%)  5/28 (17.86%)  1/3 (33.33%)  3/31 (9.68%)  3/32 (9.38%)  12/100 (12.00%)  8/60 (13.33%)  69/373 (18.50%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Diarrhoea † 1  18/69 (26.09%)  6/42 (14.29%)  7/54 (12.96%)  8/30 (26.67%)  13/69 (18.84%)  4/15 (26.67%)  5/28 (17.86%)  0/3 (0.00%)  5/31 (16.13%)  4/32 (12.50%)  18/100 (18.00%)  9/60 (15.00%)  70/373 (18.77%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dry mouth † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  2/30 (6.67%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dyspepsia † 1  4/69 (5.80%)  3/42 (7.14%)  4/54 (7.41%)  3/30 (10.00%)  6/69 (8.70%)  0/15 (0.00%)  2/28 (7.14%)  1/3 (33.33%)  1/31 (3.23%)  2/32 (6.25%)  7/100 (7.00%)  4/60 (6.67%)  26/373 (6.97%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dysphagia † 1  2/69 (2.90%)  4/42 (9.52%)  6/54 (11.11%)  1/30 (3.33%)  1/69 (1.45%)  2/15 (13.33%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  1/100 (1.00%)  1/60 (1.67%)  17/373 (4.56%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Gastrooesophageal reflux disease † 1  3/69 (4.35%)  1/42 (2.38%)  3/54 (5.56%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  2/100 (2.00%)  3/60 (5.00%)  12/373 (3.22%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Nausea † 1  32/69 (46.38%)  16/42 (38.10%)  24/54 (44.44%)  15/30 (50.00%)  32/69 (46.38%)  9/15 (60.00%)  13/28 (46.43%)  2/3 (66.67%)  12/31 (38.71%)  15/32 (46.88%)  44/100 (44.00%)  28/60 (46.67%)  170/373 (45.58%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Stomatitis † 1  1/69 (1.45%)  0/42 (0.00%)  3/54 (5.56%)  0/30 (0.00%)  3/69 (4.35%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  4/100 (4.00%)  2/60 (3.33%)  11/373 (2.95%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Vomiting † 1  22/69 (31.88%)  14/42 (33.33%)  12/54 (22.22%)  9/30 (30.00%)  19/69 (27.54%)  4/15 (26.67%)  7/28 (25.00%)  1/3 (33.33%)  8/31 (25.81%)  6/32 (18.75%)  27/100 (27.00%)  13/60 (21.67%)  102/373 (27.35%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
General disorders                                                     
Asthenia † 1  6/69 (8.70%)  8/42 (19.05%)  11/54 (20.37%)  3/30 (10.00%)  6/69 (8.70%)  2/15 (13.33%)  4/28 (14.29%)  0/3 (0.00%)  3/31 (9.68%)  6/32 (18.75%)  9/100 (9.00%)  10/60 (16.67%)  49/373 (13.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Chest discomfort † 1  1/69 (1.45%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  1/60 (1.67%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Face oedema † 1  1/69 (1.45%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  4/69 (5.80%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  5/100 (5.00%)  2/60 (3.33%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Fatigue † 1  11/69 (15.94%)  10/42 (23.81%)  16/54 (29.63%)  6/30 (20.00%)  19/69 (27.54%)  2/15 (13.33%)  4/28 (14.29%)  1/3 (33.33%)  11/31 (35.48%)  6/32 (18.75%)  30/100 (30.00%)  10/60 (16.67%)  86/373 (23.06%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Generalised oedema † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  2/100 (2.00%)  3/60 (5.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Malaise † 1  2/69 (2.90%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  3/69 (4.35%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  4/100 (4.00%)  2/60 (3.33%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Non-cardiac chest pain † 1  8/69 (11.59%)  5/42 (11.90%)  7/54 (12.96%)  1/30 (3.33%)  4/69 (5.80%)  3/15 (20.00%)  1/28 (3.57%)  0/3 (0.00%)  3/31 (9.68%)  0/32 (0.00%)  7/100 (7.00%)  1/60 (1.67%)  32/373 (8.58%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Oedema † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  4/28 (14.29%)  0/3 (0.00%)  0/31 (0.00%)  3/32 (9.38%)  0/100 (0.00%)  7/60 (11.67%)  8/373 (2.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Oedema peripheral † 1  34/69 (49.28%)  18/42 (42.86%)  24/54 (44.44%)  11/30 (36.67%)  38/69 (55.07%)  10/15 (66.67%)  21/28 (75.00%)  1/3 (33.33%)  23/31 (74.19%)  23/32 (71.88%)  61/100 (61.00%)  44/60 (73.33%)  203/373 (54.42%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pain † 1  4/69 (5.80%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  2/69 (2.90%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  2/100 (2.00%)  1/60 (1.67%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Peripheral swelling † 1  1/69 (1.45%)  1/42 (2.38%)  1/54 (1.85%)  1/30 (3.33%)  1/69 (1.45%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  3/32 (9.38%)  1/100 (1.00%)  4/60 (6.67%)  10/373 (2.68%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pyrexia † 1  8/69 (11.59%)  7/42 (16.67%)  8/54 (14.81%)  5/30 (16.67%)  9/69 (13.04%)  3/15 (20.00%)  2/28 (7.14%)  1/3 (33.33%)  2/31 (6.45%)  4/32 (12.50%)  11/100 (11.00%)  6/60 (10.00%)  49/373 (13.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hepatobiliary disorders                                                     
Hepatic steatosis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Immune system disorders                                                     
Contrast media allergy † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  3/60 (5.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Infections and infestations                                                     
Bronchitis † 1  1/69 (1.45%)  1/42 (2.38%)  3/54 (5.56%)  0/30 (0.00%)  4/69 (5.80%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  5/100 (5.00%)  0/60 (0.00%)  10/373 (2.68%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
COVID-19 † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  3/32 (9.38%)  3/100 (3.00%)  4/60 (6.67%)  7/373 (1.88%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Cellulitis † 1  3/69 (4.35%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  4/69 (5.80%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  3/31 (9.68%)  0/32 (0.00%)  7/100 (7.00%)  2/60 (3.33%)  13/373 (3.49%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Epididymitis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  0/100 (0.00%)  2/60 (3.33%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Erysipelas † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  0/100 (0.00%)  2/60 (3.33%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Herpes zoster † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  0/32 (0.00%)  2/100 (2.00%)  1/60 (1.67%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Influenza † 1  0/69 (0.00%)  3/42 (7.14%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Nasopharyngitis † 1  7/69 (10.14%)  4/42 (9.52%)  1/54 (1.85%)  1/30 (3.33%)  3/69 (4.35%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  3/31 (9.68%)  2/32 (6.25%)  6/100 (6.00%)  4/60 (6.67%)  24/373 (6.43%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Oral candidiasis † 1  0/69 (0.00%)  0/42 (0.00%)  3/54 (5.56%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  2/60 (3.33%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonia † 1  6/69 (8.70%)  5/42 (11.90%)  1/54 (1.85%)  3/30 (10.00%)  5/69 (7.25%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  2/31 (6.45%)  2/32 (6.25%)  7/100 (7.00%)  4/60 (6.67%)  27/373 (7.24%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pyuria † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Rhinitis † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Sepsis † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  1/3 (33.33%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Staphylococcal infection † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Upper respiratory tract infection † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  1/3 (33.33%)  0/31 (0.00%)  1/32 (3.13%)  1/100 (1.00%)  2/60 (3.33%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Urinary tract infection † 1  0/69 (0.00%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  7/69 (10.14%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  2/31 (6.45%)  2/32 (6.25%)  9/100 (9.00%)  2/60 (3.33%)  13/373 (3.49%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Injury, poisoning and procedural complications                                                     
Anastomotic ulcer † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Face injury † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Fall † 1  1/69 (1.45%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  2/69 (2.90%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  2/31 (6.45%)  2/32 (6.25%)  4/100 (4.00%)  4/60 (6.67%)  11/373 (2.95%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Head injury † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Limb injury † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  0/32 (0.00%)  3/100 (3.00%)  1/60 (1.67%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pelvic fracture † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Spinal compression fracture † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  2/15 (13.33%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Investigations                                                     
Alanine aminotransferase increased † 1  13/69 (18.84%)  4/42 (9.52%)  5/54 (9.26%)  3/30 (10.00%)  9/69 (13.04%)  5/15 (33.33%)  4/28 (14.29%)  0/3 (0.00%)  7/31 (22.58%)  3/32 (9.38%)  16/100 (16.00%)  7/60 (11.67%)  53/373 (14.21%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Amylase increased † 1  9/69 (13.04%)  3/42 (7.14%)  2/54 (3.70%)  1/30 (3.33%)  7/69 (10.14%)  3/15 (20.00%)  2/28 (7.14%)  0/3 (0.00%)  4/31 (12.90%)  5/32 (15.63%)  11/100 (11.00%)  7/60 (11.67%)  36/373 (9.65%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Aspartate aminotransferase increased † 1  11/69 (15.94%)  2/42 (4.76%)  4/54 (7.41%)  3/30 (10.00%)  6/69 (8.70%)  5/15 (33.33%)  2/28 (7.14%)  0/3 (0.00%)  4/31 (12.90%)  2/32 (6.25%)  10/100 (10.00%)  4/60 (6.67%)  39/373 (10.46%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Blood albumin decreased † 1  3/69 (4.35%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  5/69 (7.25%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  5/100 (5.00%)  2/60 (3.33%)  13/373 (3.49%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Blood alkaline phosphatase increased † 1  8/69 (11.59%)  1/42 (2.38%)  3/54 (5.56%)  0/30 (0.00%)  5/69 (7.25%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  3/31 (9.68%)  3/32 (9.38%)  8/100 (8.00%)  4/60 (6.67%)  25/373 (6.70%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Blood bilirubin increased † 1  3/69 (4.35%)  2/42 (4.76%)  1/54 (1.85%)  1/30 (3.33%)  1/69 (1.45%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  2/100 (2.00%)  4/60 (6.67%)  13/373 (3.49%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Blood creatinine increased † 1  16/69 (23.19%)  8/42 (19.05%)  14/54 (25.93%)  5/30 (16.67%)  24/69 (34.78%)  3/15 (20.00%)  10/28 (35.71%)  1/3 (33.33%)  10/31 (32.26%)  12/32 (37.50%)  34/100 (34.00%)  22/60 (36.67%)  103/373 (27.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Blood urine present † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
C-reactive protein increased † 1  3/69 (4.35%)  2/42 (4.76%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  1/3 (33.33%)  0/31 (0.00%)  2/32 (6.25%)  0/100 (0.00%)  2/60 (3.33%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Eastern Cooperative Oncology Group performance status worsened † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Gamma-glutamyltransferase increased † 1  9/69 (13.04%)  2/42 (4.76%)  5/54 (9.26%)  0/30 (0.00%)  3/69 (4.35%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  3/31 (9.68%)  0/32 (0.00%)  6/100 (6.00%)  2/60 (3.33%)  24/373 (6.43%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Lipase increased † 1  5/69 (7.25%)  4/42 (9.52%)  1/54 (1.85%)  4/30 (13.33%)  7/69 (10.14%)  1/15 (6.67%)  5/28 (17.86%)  0/3 (0.00%)  3/31 (9.68%)  7/32 (21.88%)  10/100 (10.00%)  12/60 (20.00%)  37/373 (9.92%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Liver function test abnormal † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Liver function test increased † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  1/100 (1.00%)  2/60 (3.33%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Lymphocyte count decreased † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  1/100 (1.00%)  3/60 (5.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Neutrophil count decreased † 1  3/69 (4.35%)  0/42 (0.00%)  2/54 (3.70%)  1/30 (3.33%)  2/69 (2.90%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  3/32 (9.38%)  3/100 (3.00%)  4/60 (6.67%)  14/373 (3.75%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Platelet count decreased † 1  3/69 (4.35%)  0/42 (0.00%)  3/54 (5.56%)  1/30 (3.33%)  5/69 (7.25%)  1/15 (6.67%)  1/28 (3.57%)  1/3 (33.33%)  1/31 (3.23%)  1/32 (3.13%)  6/100 (6.00%)  2/60 (3.33%)  17/373 (4.56%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Procalcitonin increased † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  1/3 (33.33%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Protein total decreased † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  2/31 (6.45%)  1/32 (3.13%)  2/100 (2.00%)  1/60 (1.67%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Weight decreased † 1  7/69 (10.14%)  4/42 (9.52%)  2/54 (3.70%)  4/30 (13.33%)  9/69 (13.04%)  3/15 (20.00%)  4/28 (14.29%)  1/3 (33.33%)  1/31 (3.23%)  6/32 (18.75%)  10/100 (10.00%)  10/60 (16.67%)  41/373 (10.99%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Weight increased † 1  7/69 (10.14%)  0/42 (0.00%)  2/54 (3.70%)  0/30 (0.00%)  4/69 (5.80%)  1/15 (6.67%)  3/28 (10.71%)  0/3 (0.00%)  2/31 (6.45%)  2/32 (6.25%)  6/100 (6.00%)  5/60 (8.33%)  21/373 (5.63%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
White blood cell count decreased † 1  2/69 (2.90%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  1/69 (1.45%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  1/100 (1.00%)  2/60 (3.33%)  8/373 (2.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Metabolism and nutrition disorders                                                     
Decreased appetite † 1  15/69 (21.74%)  6/42 (14.29%)  12/54 (22.22%)  8/30 (26.67%)  15/69 (21.74%)  4/15 (26.67%)  8/28 (28.57%)  0/3 (0.00%)  6/31 (19.35%)  6/32 (18.75%)  21/100 (21.00%)  14/60 (23.33%)  80/373 (21.45%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypercalcaemia † 1  1/69 (1.45%)  0/42 (0.00%)  3/54 (5.56%)  1/30 (3.33%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hyperkalaemia † 1  1/69 (1.45%)  1/42 (2.38%)  4/54 (7.41%)  1/30 (3.33%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  1/100 (1.00%)  1/60 (1.67%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypoalbuminaemia † 1  9/69 (13.04%)  4/42 (9.52%)  5/54 (9.26%)  0/30 (0.00%)  5/69 (7.25%)  1/15 (6.67%)  3/28 (10.71%)  0/3 (0.00%)  6/31 (19.35%)  5/32 (15.63%)  11/100 (11.00%)  8/60 (13.33%)  38/373 (10.19%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypocalcaemia † 1  1/69 (1.45%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  5/69 (7.25%)  1/15 (6.67%)  3/28 (10.71%)  0/3 (0.00%)  4/31 (12.90%)  8/32 (25.00%)  9/100 (9.00%)  11/60 (18.33%)  23/373 (6.17%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypokalaemia † 1  5/69 (7.25%)  2/42 (4.76%)  2/54 (3.70%)  3/30 (10.00%)  3/69 (4.35%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  4/32 (12.50%)  5/100 (5.00%)  5/60 (8.33%)  23/373 (6.17%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypomagnesaemia † 1  2/69 (2.90%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  2/100 (2.00%)  2/60 (3.33%)  7/373 (1.88%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hyponatraemia † 1  1/69 (1.45%)  2/42 (4.76%)  3/54 (5.56%)  0/30 (0.00%)  3/69 (4.35%)  2/15 (13.33%)  1/28 (3.57%)  1/3 (33.33%)  0/31 (0.00%)  2/32 (6.25%)  3/100 (3.00%)  3/60 (5.00%)  15/373 (4.02%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypophagia † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypophosphataemia † 1  9/69 (13.04%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  3/69 (4.35%)  0/15 (0.00%)  3/28 (10.71%)  0/3 (0.00%)  4/31 (12.90%)  0/32 (0.00%)  7/100 (7.00%)  3/60 (5.00%)  20/373 (5.36%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal and connective tissue disorders                                                     
Arthralgia † 1  6/69 (8.70%)  3/42 (7.14%)  7/54 (12.96%)  0/30 (0.00%)  8/69 (11.59%)  3/15 (20.00%)  7/28 (25.00%)  1/3 (33.33%)  2/31 (6.45%)  2/32 (6.25%)  10/100 (10.00%)  9/60 (15.00%)  39/373 (10.46%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Back pain † 1  8/69 (11.59%)  7/42 (16.67%)  10/54 (18.52%)  2/30 (6.67%)  11/69 (15.94%)  2/15 (13.33%)  4/28 (14.29%)  1/3 (33.33%)  11/31 (35.48%)  7/32 (21.88%)  22/100 (22.00%)  11/60 (18.33%)  63/373 (16.89%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Flank pain † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  1/3 (33.33%)  1/31 (3.23%)  0/32 (0.00%)  2/100 (2.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Joint swelling † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  2/28 (7.14%)  1/3 (33.33%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  2/60 (3.33%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Muscle spasms † 1  4/69 (5.80%)  6/42 (14.29%)  3/54 (5.56%)  1/30 (3.33%)  1/69 (1.45%)  3/15 (20.00%)  3/28 (10.71%)  0/3 (0.00%)  2/31 (6.45%)  3/32 (9.38%)  3/100 (3.00%)  6/60 (10.00%)  26/373 (6.97%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Muscular weakness † 1  1/69 (1.45%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  3/31 (9.68%)  2/32 (6.25%)  4/100 (4.00%)  3/60 (5.00%)  10/373 (2.68%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal chest pain † 1  2/69 (2.90%)  1/42 (2.38%)  3/54 (5.56%)  2/30 (6.67%)  6/69 (8.70%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  7/100 (7.00%)  2/60 (3.33%)  18/373 (4.83%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Musculoskeletal pain † 1  3/69 (4.35%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  2/60 (3.33%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Myalgia † 1  4/69 (5.80%)  3/42 (7.14%)  1/54 (1.85%)  1/30 (3.33%)  5/69 (7.25%)  2/15 (13.33%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  0/32 (0.00%)  7/100 (7.00%)  1/60 (1.67%)  19/373 (5.09%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Neck pain † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  4/69 (5.80%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  5/100 (5.00%)  2/60 (3.33%)  8/373 (2.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pain in extremity † 1  6/69 (8.70%)  2/42 (4.76%)  3/54 (5.56%)  1/30 (3.33%)  7/69 (10.14%)  1/15 (6.67%)  3/28 (10.71%)  0/3 (0.00%)  5/31 (16.13%)  3/32 (9.38%)  12/100 (12.00%)  6/60 (10.00%)  31/373 (8.31%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Nervous system disorders                                                     
Disturbance in attention † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dizziness † 1  4/69 (5.80%)  5/42 (11.90%)  1/54 (1.85%)  2/30 (6.67%)  9/69 (13.04%)  2/15 (13.33%)  3/28 (10.71%)  1/3 (33.33%)  3/31 (9.68%)  4/32 (12.50%)  12/100 (12.00%)  7/60 (11.67%)  34/373 (9.12%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dysarthria † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dysgeusia † 1  3/69 (4.35%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  0/100 (0.00%)  3/60 (5.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Headache † 1  6/69 (8.70%)  4/42 (9.52%)  3/54 (5.56%)  2/30 (6.67%)  9/69 (13.04%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  2/31 (6.45%)  1/32 (3.13%)  11/100 (11.00%)  3/60 (5.00%)  30/373 (8.04%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypoaesthesia † 1  1/69 (1.45%)  1/42 (2.38%)  0/54 (0.00%)  1/30 (3.33%)  2/69 (2.90%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Neuropathy peripheral † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  2/69 (2.90%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  3/32 (9.38%)  2/100 (2.00%)  3/60 (5.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Paraesthesia † 1  1/69 (1.45%)  3/42 (7.14%)  2/54 (3.70%)  0/30 (0.00%)  3/69 (4.35%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  3/31 (9.68%)  2/32 (6.25%)  6/100 (6.00%)  3/60 (5.00%)  15/373 (4.02%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Somnolence † 1  2/69 (2.90%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Syncope † 1  0/69 (0.00%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  2/60 (3.33%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Taste disorder † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  2/100 (2.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Tremor † 1  0/69 (0.00%)  2/42 (4.76%)  2/54 (3.70%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  2/31 (6.45%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Psychiatric disorders                                                     
Anxiety † 1  0/69 (0.00%)  3/42 (7.14%)  4/54 (7.41%)  0/30 (0.00%)  3/69 (4.35%)  1/15 (6.67%)  2/28 (7.14%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  4/100 (4.00%)  3/60 (5.00%)  15/373 (4.02%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Confusional state † 1  2/69 (2.90%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  0/69 (0.00%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Depression † 1  1/69 (1.45%)  1/42 (2.38%)  2/54 (3.70%)  0/30 (0.00%)  3/69 (4.35%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  3/31 (9.68%)  2/32 (6.25%)  6/100 (6.00%)  2/60 (3.33%)  12/373 (3.22%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dysphoria † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Insomnia † 1  7/69 (10.14%)  3/42 (7.14%)  3/54 (5.56%)  1/30 (3.33%)  6/69 (8.70%)  0/15 (0.00%)  5/28 (17.86%)  0/3 (0.00%)  3/31 (9.68%)  6/32 (18.75%)  9/100 (9.00%)  11/60 (18.33%)  34/373 (9.12%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Sleep disorder † 1  1/69 (1.45%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  0/69 (0.00%)  2/15 (13.33%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Renal and urinary disorders                                                     
Dysuria † 1  1/69 (1.45%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  1/3 (33.33%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Renal failure † 1  1/69 (1.45%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Reproductive system and breast disorders                                                     
Breast pain † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  2/60 (3.33%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Breast swelling † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Oedema genital † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  2/28 (7.14%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  0/100 (0.00%)  3/60 (5.00%)  3/373 (0.80%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Respiratory, thoracic and mediastinal disorders                                                     
Cough † 1  9/69 (13.04%)  9/42 (21.43%)  9/54 (16.67%)  4/30 (13.33%)  11/69 (15.94%)  2/15 (13.33%)  7/28 (25.00%)  0/3 (0.00%)  7/31 (22.58%)  3/32 (9.38%)  18/100 (18.00%)  10/60 (16.67%)  61/373 (16.35%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dysphonia † 1  4/69 (5.80%)  1/42 (2.38%)  0/54 (0.00%)  1/30 (3.33%)  2/69 (2.90%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  0/32 (0.00%)  4/100 (4.00%)  1/60 (1.67%)  11/373 (2.95%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dyspnoea † 1  11/69 (15.94%)  15/42 (35.71%)  11/54 (20.37%)  5/30 (16.67%)  16/69 (23.19%)  5/15 (33.33%)  6/28 (21.43%)  2/3 (66.67%)  6/31 (19.35%)  6/32 (18.75%)  22/100 (22.00%)  12/60 (20.00%)  83/373 (22.25%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dyspnoea exertional † 1  0/69 (0.00%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  3/69 (4.35%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  1/32 (3.13%)  3/100 (3.00%)  2/60 (3.33%)  8/373 (2.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Emphysema † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Epistaxis † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  1/30 (3.33%)  3/69 (4.35%)  2/15 (13.33%)  1/28 (3.57%)  0/3 (0.00%)  0/31 (0.00%)  3/32 (9.38%)  3/100 (3.00%)  4/60 (6.67%)  11/373 (2.95%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Haemoptysis † 1  3/69 (4.35%)  3/42 (7.14%)  3/54 (5.56%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  1/3 (33.33%)  3/31 (9.68%)  1/32 (3.13%)  4/100 (4.00%)  2/60 (3.33%)  16/373 (4.29%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypoxia † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  2/69 (2.90%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  0/32 (0.00%)  4/100 (4.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Interstitial lung disease † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Oropharyngeal pain † 1  1/69 (1.45%)  1/42 (2.38%)  1/54 (1.85%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  1/3 (33.33%)  3/31 (9.68%)  0/32 (0.00%)  4/100 (4.00%)  0/60 (0.00%)  8/373 (2.14%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pleural effusion † 1  3/69 (4.35%)  4/42 (9.52%)  3/54 (5.56%)  0/30 (0.00%)  3/69 (4.35%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  2/31 (6.45%)  2/32 (6.25%)  5/100 (5.00%)  2/60 (3.33%)  17/373 (4.56%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pleurisy † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  2/100 (2.00%)  3/60 (5.00%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pneumonitis † 1  3/69 (4.35%)  0/42 (0.00%)  0/54 (0.00%)  1/30 (3.33%)  4/69 (5.80%)  0/15 (0.00%)  1/28 (3.57%)  1/3 (33.33%)  0/31 (0.00%)  1/32 (3.13%)  4/100 (4.00%)  2/60 (3.33%)  11/373 (2.95%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Productive cough † 1  3/69 (4.35%)  0/42 (0.00%)  2/54 (3.70%)  4/30 (13.33%)  4/69 (5.80%)  0/15 (0.00%)  3/28 (10.71%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  5/100 (5.00%)  5/60 (8.33%)  19/373 (5.09%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pulmonary embolism † 1  1/69 (1.45%)  4/42 (9.52%)  2/54 (3.70%)  0/30 (0.00%)  2/69 (2.90%)  2/15 (13.33%)  2/28 (7.14%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  2/100 (2.00%)  4/60 (6.67%)  15/373 (4.02%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Rhinitis allergic † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  3/31 (9.68%)  1/32 (3.13%)  3/100 (3.00%)  2/60 (3.33%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Rhinorrhoea † 1  1/69 (1.45%)  1/42 (2.38%)  0/54 (0.00%)  1/30 (3.33%)  2/69 (2.90%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  1/32 (3.13%)  4/100 (4.00%)  2/60 (3.33%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Skin and subcutaneous tissue disorders                                                     
Alopecia † 1  0/69 (0.00%)  3/42 (7.14%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  3/32 (9.38%)  2/100 (2.00%)  4/60 (6.67%)  10/373 (2.68%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dermatitis acneiform † 1  1/69 (1.45%)  0/42 (0.00%)  1/54 (1.85%)  0/30 (0.00%)  2/69 (2.90%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  3/100 (3.00%)  2/60 (3.33%)  7/373 (1.88%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Dry skin † 1  9/69 (13.04%)  1/42 (2.38%)  2/54 (3.70%)  1/30 (3.33%)  2/69 (2.90%)  2/15 (13.33%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  3/100 (3.00%)  1/60 (1.67%)  19/373 (5.09%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Eczema † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  0/32 (0.00%)  3/100 (3.00%)  1/60 (1.67%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pruritus † 1  7/69 (10.14%)  6/42 (14.29%)  3/54 (5.56%)  0/30 (0.00%)  10/69 (14.49%)  2/15 (13.33%)  2/28 (7.14%)  0/3 (0.00%)  3/31 (9.68%)  2/32 (6.25%)  13/100 (13.00%)  4/60 (6.67%)  35/373 (9.38%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Pruritus allergic † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Rash † 1  3/69 (4.35%)  1/42 (2.38%)  4/54 (7.41%)  1/30 (3.33%)  6/69 (8.70%)  2/15 (13.33%)  0/28 (0.00%)  0/3 (0.00%)  4/31 (12.90%)  3/32 (9.38%)  10/100 (10.00%)  3/60 (5.00%)  24/373 (6.43%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Rash maculo-papular † 1  2/69 (2.90%)  0/42 (0.00%)  2/54 (3.70%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  2/31 (6.45%)  0/32 (0.00%)  2/100 (2.00%)  0/60 (0.00%)  6/373 (1.61%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Skin induration † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  0/32 (0.00%)  1/100 (1.00%)  0/60 (0.00%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Skin lesion † 1  0/69 (0.00%)  1/42 (2.38%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  1/100 (1.00%)  2/60 (3.33%)  4/373 (1.07%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Stasis dermatitis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  0/32 (0.00%)  0/100 (0.00%)  0/60 (0.00%)  1/373 (0.27%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Vascular disorders                                                     
Deep vein thrombosis † 1  0/69 (0.00%)  2/42 (4.76%)  2/54 (3.70%)  0/30 (0.00%)  1/69 (1.45%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  2/32 (6.25%)  2/100 (2.00%)  2/60 (3.33%)  9/373 (2.41%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Embolism † 1  1/69 (1.45%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  1/69 (1.45%)  1/15 (6.67%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  1/32 (3.13%)  2/100 (2.00%)  1/60 (1.67%)  5/373 (1.34%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypertension † 1  4/69 (5.80%)  0/42 (0.00%)  1/54 (1.85%)  1/30 (3.33%)  2/69 (2.90%)  1/15 (6.67%)  1/28 (3.57%)  0/3 (0.00%)  2/31 (6.45%)  1/32 (3.13%)  4/100 (4.00%)  2/60 (3.33%)  13/373 (3.49%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Hypotension † 1  4/69 (5.80%)  1/42 (2.38%)  2/54 (3.70%)  1/30 (3.33%)  5/69 (7.25%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  1/31 (3.23%)  5/32 (15.63%)  6/100 (6.00%)  5/60 (8.33%)  19/373 (5.09%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
Superficial vein thrombosis † 1  0/69 (0.00%)  0/42 (0.00%)  0/54 (0.00%)  0/30 (0.00%)  0/69 (0.00%)  0/15 (0.00%)  0/28 (0.00%)  0/3 (0.00%)  0/31 (0.00%)  2/32 (6.25%)  0/100 (0.00%)  2/60 (3.33%)  2/373 (0.54%)  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0  /0 
1
Term from vocabulary, MedDRA (26.0)
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
EMail: Novartis.email@novartis.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT02414139    
Other Study ID Numbers: CINC280A2201
2014-003850-15 ( EudraCT Number )
First Submitted: March 31, 2015
First Posted: April 10, 2015
Results First Submitted: April 19, 2023
Results First Posted: March 20, 2024
Last Update Posted: March 20, 2024