Download PDF

Clinical Trial Results:
A phase II, multicenter study of oral cMET inhibitor INC280 in adult patients with EGFR wild-type (wt), advanced non-small cell lung cancer (NSCLC)

Summary
EudraCT number	2014-003850-15
Trial protocol	AT DE ES NL FR BE SE GB IT
Global end of trial date	16 May 2023

Results information
Results version number	v1(current)
This version publication date	07 Mar 2024
First version publication date	07 Mar 2024
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

CINC280A2201

ISRCTN number

US NCT number

NCT02414139

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma AG

Sponsor organisation address

Novartis Campus, Basel, Switzerland,

Public contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

Scientific contact

Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@novartis.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

16 May 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

16 May 2023

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study was to evaluate the antitumor activity of capmatinib, as measured by overall response rate (ORR) by Blinded Independent Review Committee (BIRC) assessment, by cohort.

Protection of trial subjects

The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.

Background therapy

Evidence for comparator

Actual start date of recruitment

11 Jun 2015

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Argentina: 3

Country: Number of subjects enrolled

Austria: 15

Country: Number of subjects enrolled

Belgium: 12

Country: Number of subjects enrolled

France: 31

Country: Number of subjects enrolled

Germany: 64

Country: Number of subjects enrolled

Israel: 6

Country: Number of subjects enrolled

Italy: 30

Country: Number of subjects enrolled

Japan: 46

Country: Number of subjects enrolled

Korea, Republic of: 21

Country: Number of subjects enrolled

Lebanon: 4

Country: Number of subjects enrolled

Mexico: 1

Country: Number of subjects enrolled

Netherlands: 26

Country: Number of subjects enrolled

Norway: 2

Country: Number of subjects enrolled

Russian Federation: 16

Country: Number of subjects enrolled

Singapore: 7

Country: Number of subjects enrolled

Spain: 36

Country: Number of subjects enrolled

Sweden: 2

Country: Number of subjects enrolled

Taiwan: 5

Country: Number of subjects enrolled

United Kingdom: 4

Country: Number of subjects enrolled

United States: 42

Worldwide total number of subjects

373

EEA total number of subjects

218

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

147

From 65 to 84 years

217

85 years and over

Subject disposition

Top of page

Recruitment details

Participants were enrolled in 95 centers across 20 countries

Screening details

Screening assessments were conducted up to 28 days prior to the start of study treatment

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Cohort 1a: 2/3L, MET GCN ≥ 10

Arm description

Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 1a, capmatinib was administered in a fasted state.

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Arm description

Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 1b, capmatinib was administered in a fasted state.

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Arm description

Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 2, capmatinib was administered in a fasted state.

Cohort 3: 2/3L, MET GCN < 4

Arm description

Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 3, capmatinib was administered in a fasted state.

Cohort 4: 2/3L, Mutant

Arm description

Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 4, capmatinib was administered in a fasted state.

Cohort 5a: 1L, MET GCN ≥10

Arm description

Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 5a, capmatinib was administered in a fasted state.

Cohort 5b: 1L, Mutant

Arm description

Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 5b, capmatinib was administered in a fasted state.

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Arm description

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)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 6, capmatinib was administered either with or without food.

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Arm description

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)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 6, capmatinib was administered either with or without food.

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Arm description

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)

Arm type

Experimental

Investigational medicinal product name

Capmatinib

Investigational medicinal product code

INC280

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Capmatinib was administered orally, at a dose of 400 mg on a continuous twice daily dosing schedule. For participants in Cohort 7, capmatinib was administered either with or without food.

Number of subjects in period 1	Cohort 1a: 2/3L, MET GCN ≥ 10	Cohort 1b: 2/3L, 6 ≤ MET GCN < 10	Cohort 2: 2/3L, 4 ≤ MET GCN < 6	Cohort 3: 2/3L, MET GCN < 4	Cohort 4: 2/3L, Mutant	Cohort 5a: 1L, MET GCN ≥10	Cohort 5b: 1L, Mutant	Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10	Cohort 6.2 (expansion of Cohort 4): 2L, Mutant	Cohort 7 (expansion of Cohort 5b): 1L, Mutant
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
Adverse event, serious fatal	-	-	1	1	-	-	-	-	-	1
Physician decision	5	4	6	1	4	-	2	-	1	4
Adverse event, non-fatal	11	6	8	5	14	3	6	1	6	8
Protocol deviation	-	-	1	-	-	-	-	-	-	-
Subject/Guardian decision	5	1	1	2	5	-	2	-	1	1
Study terminated (as per protocol) by Sponsor	-	-	-	-	3	-	2	-	3	4
Progressive disease	48	31	37	21	43	12	16	2	20	14

Baseline characteristics

Top of page

Reporting group title

Cohort 1a: 2/3L, MET GCN ≥ 10

Reporting group description

Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)

Reporting group title

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Reporting group description

Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)

Reporting group title

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Reporting group description

Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)

Reporting group title

Cohort 3: 2/3L, MET GCN < 4

Reporting group description

Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)

Reporting group title

Cohort 4: 2/3L, Mutant

Reporting group description

Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)

Reporting group title

Cohort 5a: 1L, MET GCN ≥10

Reporting group description

Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)

Reporting group title

Cohort 5b: 1L, Mutant

Reporting group description

Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)

Reporting group title

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Reporting group description

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)

Reporting group title

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Reporting group description

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)

Reporting group title

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Reporting group description

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)

Reporting group values	Cohort 1a: 2/3L, MET GCN ≥ 10	Cohort 1b: 2/3L, 6 ≤ MET GCN < 10	Cohort 2: 2/3L, 4 ≤ MET GCN < 6	Cohort 3: 2/3L, MET GCN < 4	Cohort 4: 2/3L, Mutant	Cohort 5a: 1L, MET GCN ≥10	Cohort 5b: 1L, Mutant	Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10	Cohort 6.2 (expansion of Cohort 4): 2L, Mutant	Cohort 7 (expansion of Cohort 5b): 1L, Mutant	Total
Number of subjects	69	42	54	30	69	15	28	3	31	32	373
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	41	29	30	16	14	5	3	2	4	3	147
From 65-84 years	28	13	24	14	51	8	24	1	27	27	217
85 years and over	0	0	0	0	4	2	1	0	0	2	9
Age Continuous
Units: Years
arithmetic mean (standard deviation)	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 )	-
Sex: Female, Male
Units: Participants
Female	15	21	15	11	40	4	18	1	16	23	164
Male	54	21	39	19	29	11	10	2	15	9	209
Race/Ethnicity, Customized
Units: Subjects
Asian	17	4	14	11	19	6	4	1	5	3	84
Black	1	0	0	0	0	0	0	0	1	1	3
Caucasian	51	38	40	19	49	9	24	1	24	26	281
Native American	0	0	0	0	1	0	0	0	1	0	2
Unknown	0	0	0	0	0	0	0	1	0	0	1
Other	0	0	0	0	0	0	0	0	0	2	2

End points

Top of page

Reporting group title

Cohort 1a: 2/3L, MET GCN ≥ 10

Reporting group description

Pre-treated patients with MET GCN ≥ 10 treated with INC280 at 400mg BID as second or third line (2/3L)

Reporting group title

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Reporting group description

Pre-treated patients with MET GCN ≥ 6 and < 10 treated with INC280 at 400 mg BID as second or third line (2/3L)

Reporting group title

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Reporting group description

Pre-treated patients with MET GCN ≥ 4 and < 6 treated with INC280 at 400mg BID as second or third line (2/3L)

Reporting group title

Cohort 3: 2/3L, MET GCN < 4

Reporting group description

Pre-treated patients with MET GCN < 4 treated with INC280 at 400mg BID as second or third line (2/3L)

Reporting group title

Cohort 4: 2/3L, Mutant

Reporting group description

Pre-treated patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as second or third line (2/3L)

Reporting group title

Cohort 5a: 1L, MET GCN ≥10

Reporting group description

Treatment-naïve patients with MET GCN ≥10 treated with INC280 at 400mg BID as first-line (1L)

Reporting group title

Cohort 5b: 1L, Mutant

Reporting group description

Treatment-naïve patients with MET mutation regardless of MET GCN treated with INC280 at 400mg BID as first line (1L)

Reporting group title

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Reporting group description

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)

Reporting group title

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Reporting group description

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)

Reporting group title

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Reporting group description

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)

Subject analysis set title

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Subject analysis set type

Sub-group analysis

Subject analysis set description

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)

Subject analysis set title

Cohort 5b + Cohort 7: 1L, Mutant

Subject analysis set type

Sub-group analysis

Subject analysis set description

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)

Subject analysis set title

Cohorts 1-5: Capmatinib administered in fasted state (PAS)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state and provided at least one evaluable PK concentration (for capmatinib or metabolite CMN288) (PK analysis set or PAS)

Subject analysis set title

Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants from Cohorts 1a, 1b, 2, 3, 4, 5a and 5b who received capmatinib in fasted state and had an extensive PK collection schedule and provided at least one evaluable PK profile (for INC280 or metabolite CMN288) (Full PK analysis set or Full PAS)

Subject analysis set title

Cohorts 6-7: Capmatinib administered with/without food (PAS)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants from Cohorts 6 and 7 who received capmatinib with or without food and provided at least one evaluable PK concentration (for capmatinib or metabolite CMN288) (PK analysis set or PAS)

Subject analysis set title

All participants

Subject analysis set type

Full analysis

Subject analysis set description

All participants

Primary: Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) assessment

Top of page

End point title

Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) assessment ^[1]

End point 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.

End point type

Primary

End point timeframe

Up to approximately 5 years

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were planned for this endpoint

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

100

Units: Percentage of Participants

number (confidence interval 95%)

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)

No statistical analyses for this end point

Secondary: Duration of Response (DOR) by BIRC assessment

Top of page

End point title

Duration of Response (DOR) by BIRC assessment

End point 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. 9999= not estimable

End point type

Secondary

End point timeframe

Up to approximately 5 years

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

0 ^[2]

Units: Months

median (confidence interval 95%)

8.31 (4.17 to 15.44)

24.94 (2.69 to 24.94)

9.66 (4.17 to 9999)

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)

( to )

9.05 (4.17 to 27.60)

16.59 (8.34 to 9999)

9.72 (5.62 to 12.98)

16.59 (8.41 to 22.11)

Notes
[2] - No participants had confirmed PR or CR

No statistical analyses for this end point

Secondary: ORR by investigator assessment

Top of page

End point title

ORR by investigator assessment

End point 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.

End point type

Secondary

End point timeframe

Up to approximately 5 years

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

100

Units: Percentage of participants

number (confidence interval 95%)

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)

No statistical analyses for this end point

Secondary: DOR by investigator assessment

Top of page

End point title

DOR by investigator assessment

End point 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. 9999= not estimable

End point type

Secondary

End point timeframe

Up to approximately 5 years

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

0 ^[3]

Units: Months

median (confidence interval 95%)

6.80 (4.21 to 20.73)

6.93 (5.75 to 8.34)

19.48 (2.83 to 9999)

6.93 (-9999 to 9999)

8.31 (4.34 to 12.06)

9.66 (4.01 to 17.08)

13.83 (4.27 to 25.33)

( to )

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)

Notes
[3] - No participants had confirmed PR or CR

No statistical analyses for this end point

Secondary: Time to Response (TTR) by BIRC assessment

Top of page

End point title

Time to Response (TTR) by BIRC assessment

End point 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.

End point type

Secondary

End point timeframe

Up to approximately 5 years

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

0 ^[4]

Units: Months

median (full range (min-max))

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)

( to )

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)

Notes
[4] - No participant had confirmed PR or CR

No statistical analyses for this end point

Secondary: TTR by investigator assessment

Top of page

End point title

TTR by investigator assessment

End point 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.

End point type

Secondary

End point timeframe

Up to approximately 5 years

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

0 ^[5]

Units: Months

median (full range (min-max))

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)

( to )

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)

Notes
[5] - No participants had confirmed PR or CR

No statistical analyses for this end point

Secondary: Disease Control Rate (DCR)

Top of page

End point title

Disease Control Rate (DCR)

End point 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.

End point type

Secondary

End point timeframe

Up to approximately 5 years

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

100

Units: Percentage of participants

number (confidence interval 95%)

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)

No statistical analyses for this end point

Secondary: Progression-Free Survival

Top of page

End point title

Progression-Free Survival

End point description

Time from start of treatment to the date of the first documented progression or death due to any cause per RECIST 1.1 both 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

End point type

Secondary

End point timeframe

Up to approximately 5 years

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

100

Units: Months

median (confidence interval 95%)

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)

No statistical analyses for this end point

Secondary: Overall Survival (OS)

Top of page

End point title

Overall Survival (OS)

End point 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. 9999= not estimable

End point type

Secondary

End point timeframe

Up to approximately 6 years

Cohort 1a: 2/3L, MET GCN ≥ 10

Cohort 1b: 2/3L, 6 ≤ MET GCN < 10

Cohort 2: 2/3L, 4 ≤ MET GCN < 6

Cohort 3: 2/3L, MET GCN < 4

Cohort 4: 2/3L, Mutant

Cohort 5a: 1L, MET GCN ≥10

Cohort 5b: 1L, Mutant

Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10

Cohort 6.2 (expansion of Cohort 4): 2L, Mutant

Cohort 7 (expansion of Cohort 5b): 1L, Mutant

Cohort 4 + Cohort 6.2: 2/3L, Mutant

Cohort 5b + Cohort 7: 1L, Mutant

Number of subjects analysed

100

Units: Months

median (confidence interval 95%)

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 (4.80 to 9999)

20.76 (12.42 to 43.93)

4.14 (2.07 to 9999)

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)

No statistical analyses for this end point

Secondary: Pharmacokinetic (PK) concentrations of capmatinib

Top of page

End point title

Pharmacokinetic (PK) concentrations of capmatinib

End point 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.

End point type

Secondary

End point timeframe

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

End point values	Cohorts 1-5: Capmatinib administered in fasted state (PAS)	Cohorts 6-7: Capmatinib administered with/without food (PAS)
Number of subjects analysed	275	54
Units: nanogram/mililiter (ng/ml)
arithmetic mean (standard deviation)
Cycle 1 Day 1- pre-dose (n= 275 / 54)	0.00 ( 0.00 )	0.00 ( 0.00 )
Cycle 1 Day 1- 2 hours post-dose (n= 275 / 53)	3360 ( 1920 )	3060 ( 1780 )
Cycle 1 Day 15 - pre-dose (n= 176 / 29 )	727 ( 781 )	663 ( 806 )
Cycle 1 Day 15- 2 hours post-dose (n= 209 / 47)	4100 ( 2100 )	4340 ( 2000 )
Cycle 3 Day 1 - pre-dose (n= 96 / 18)	687 ( 1000 )	672 ( 745 )

No statistical analyses for this end point

Secondary: Area under the plasma concentration-time curve from zero to time infinity (AUCinf) of CMN288

Top of page

End point title

Area under the plasma concentration-time curve from zero to time infinity (AUCinf) of CMN288

End point 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

End point type

Secondary

End point timeframe

Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days

End point values	Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)
Number of subjects analysed	27
Units: ng*h/ml
arithmetic mean (standard deviation)
Cycle 1 Day 1	9020 ( 5060 )

No statistical analyses for this end point

Secondary: Area under the plasma concentration-time curve from zero to time infinity (AUCinf) of capmatinib

Top of page

End point title

Area under the plasma concentration-time curve from zero to time infinity (AUCinf) of capmatinib

End point description

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

End point type

Secondary

End point timeframe

Cycle 1 Day 1 at pre-dose, 0.5, 1, 2, 4, 6 and 8 hours post-dose. Each Cycle is 21 days

End point values	Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)
Number of subjects analysed	44
Units: nanogram * hour / mililiter (ng*h/ml)
arithmetic mean (standard deviation)	17000 ( 7770 )

No statistical analyses for this end point

Secondary: Maximum concentration (Cmax) of capmatinib

Top of page

End point title

Maximum concentration (Cmax) of capmatinib

End point 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

End point type

Secondary

End point timeframe

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

End point values	Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)
Number of subjects analysed	55
Units: ng/ml
arithmetic mean (standard deviation)
Cycle 1 Day 1 (n=55)	4230 ( 2290 )
Cycle 1 Day 15 (n=44)	5450 ( 2560 )

No statistical analyses for this end point

Secondary: Maximum concentration (Cmax) of CMN288

Top of page

End point title

Maximum concentration (Cmax) of CMN288

End point description

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

End point type

Secondary

End point timeframe

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

End point values	Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)
Number of subjects analysed	51
Units: ng/ml
arithmetic mean (standard deviation)
Cycle 1 Day 1 (n= 51)	1910 ( 1420 )
Cycle 1 Day 15 (n= 42)	1420 ( 725 )

No statistical analyses for this end point

Secondary: Time to reach maximum concentration (Tmax) of CMN288

Top of page

End point title

Time to reach maximum concentration (Tmax) of CMN288

End point 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

End point type

Secondary

End point timeframe

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

End point values	Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)
Number of subjects analysed	51
Units: hour
median (full range (min-max))
Cycle 1 Day 1 (n= 51)	1.93 (0.950 to 4.03)
Cycle 1 Day 15 (n= 42)	1.91 (0.883 to 7.98)

No statistical analyses for this end point

Secondary: Time to reach maximum concentration (Tmax) of capmatinib

Top of page

End point title

Time to reach maximum concentration (Tmax) of capmatinib

End point 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

End point type

Secondary

End point timeframe

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

End point values	Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)
Number of subjects analysed	55
Units: hour
median (full range (min-max))
Cycle 1 Day 1 (n= 55)	1.87 (0.583 to 4.03)
Cycle 1 Day 15 (n= 44)	1.09 (0.5 to 6.07)

No statistical analyses for this end point

Secondary: Elimination half-life (T1/2) of capmatinib

Top of page

End point title

Elimination half-life (T1/2) of capmatinib

End point 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

End point type

Secondary

End point timeframe

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

End point values	Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)
Number of subjects analysed	47
Units: hour
arithmetic mean (standard deviation)
Cycle 1 Day 1 (n= 47)	1.87 ( 0.947 )
Cycle 1 Day 15 (n= 37)	2.40 ( 0.652 )

No statistical analyses for this end point

Secondary: Elimination half-life (T1/2) of CMN288

Top of page

End point title

Elimination half-life (T1/2) of CMN288

End point 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

End point type

Secondary

End point timeframe

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

End point values	Cohorts 1-5:Capmatinib administered in fasted state (Full PAS)
Number of subjects analysed	40
Units: hour
arithmetic mean (standard deviation)
Cycle 1 Day 1 (n= 40)	3.14 ( 1.42 )
Cycle 1 Day 15 (n= 34)	3.06 ( 0.949 )

No statistical analyses for this end point

Post-hoc: All collected deaths

Top of page

End point title

All collected deaths

End point 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.

End point type

Post-hoc

End point timeframe

On-treatment: Up to approximately 5.5 years. Post-treatment efficacy/survival follow-up: Up to approximately 6 years

End point values	Cohort 1a: 2/3L, MET GCN ≥ 10	Cohort 1b: 2/3L, 6 ≤ MET GCN < 10	Cohort 2: 2/3L, 4 ≤ MET GCN < 6	Cohort 3: 2/3L, MET GCN < 4	Cohort 4: 2/3L, Mutant	Cohort 5a: 1L, MET GCN ≥10	Cohort 5b: 1L, Mutant	Cohort 6.1 (expansion of Cohort 1a): 2L, MET GCN ≥ 10	Cohort 6.2 (expansion of Cohort 4): 2L, Mutant	Cohort 7 (expansion of Cohort 5b): 1L, Mutant	Cohort 4 + Cohort 6.2: 2/3L, Mutant	Cohort 5b + Cohort 7: 1L, Mutant	All participants
Number of subjects analysed	69	42	54	30	69	15	28	3	31	32	100	60	373
Units: Participants
On-treatment	10	7	12	4	14	0	5	1	5	5	19	10	63
Post-treatment efficacy/survival follow-up	44	26	34	22	44	13	13	2	17	16	61	29	231
All deaths	54	33	46	26	58	13	18	3	22	21	80	39	294

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

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.

Adverse event reporting additional description

Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

26.0

Reporting group title

Cohort 1a: On-treatment

Reporting group description

AEs collected during the on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 1b: On-treatment

Reporting group description

AEs collected during the on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 2: On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 3: On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 5a: On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 4: On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 5b: On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 6.1 (expansion of Cohort 1a): On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 6.2 (expansion of Cohort 4): On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 7 (expansion of Cohort 5b): On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 5b + Cohort 7: On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

Cohort 4 + Cohort 6.2: On-treatment

Reporting group description

AEs collected during on-treatment period (up to 30 days post-treatment)

Reporting group title

All patients: On-treatment

Reporting group description

AEs collected during the on-treatment period (up to 30 days post-treatment)

Cohort 1a: On-treatment

Cohort 1b: On-treatment

Cohort 2: On-treatment

Cohort 3: On-treatment

Cohort 5a: On-treatment

Cohort 4: 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 5b + Cohort 7: On-treatment

Cohort 4 + Cohort 6.2: On-treatment

All patients: On-treatment

Total subjects affected by serious adverse events

subjects affected / exposed

42 / 69 (60.87%)

21 / 42 (50.00%)

30 / 54 (55.56%)

15 / 30 (50.00%)

9 / 15 (60.00%)

38 / 69 (55.07%)

14 / 28 (50.00%)

2 / 3 (66.67%)

14 / 31 (45.16%)

17 / 32 (53.13%)

31 / 60 (51.67%)

52 / 100 (52.00%)

202 / 373 (54.16%)

number of deaths (all causes)

number of deaths resulting from adverse events

Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Adenocarcinoma gastric

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Cancer pain

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

Breast cancer

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Rectal cancer

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Tumour pain

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Tumour haemorrhage

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Squamous cell carcinoma of skin

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Vascular disorders

Embolism

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypertension

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Jugular vein thrombosis

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Peripheral ischaemia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Thrombosis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Superior vena cava syndrome

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

Venous thrombosis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Asthenia

subjects affected / exposed

3 / 69 (4.35%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 3

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Drug withdrawal syndrome

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Fatigue

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

General physical health deterioration

subjects affected / exposed

3 / 69 (4.35%)

3 / 42 (7.14%)

2 / 54 (3.70%)

1 / 30 (3.33%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

1 / 100 (1.00%)

11 / 373 (2.95%)

occurrences causally related to treatment / all

0 / 4

0 / 3

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 12

deaths causally related to treatment / all

0 / 0

Malaise

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Generalised oedema

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Non-cardiac chest pain

subjects affected / exposed

2 / 69 (2.90%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

4 / 373 (1.07%)

occurrences causally related to treatment / all

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 4

deaths causally related to treatment / all

0 / 0

Pain

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

Oedema peripheral

subjects affected / exposed

2 / 69 (2.90%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

2 / 32 (6.25%)

3 / 60 (5.00%)

0 / 100 (0.00%)

6 / 373 (1.61%)

occurrences causally related to treatment / all

2 / 2

0 / 0

1 / 1

0 / 0

0 / 3

0 / 0

1 / 2

1 / 5

0 / 0

4 / 8

deaths causally related to treatment / all

0 / 0

Peripheral swelling

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

1 / 15 (6.67%)

2 / 69 (2.90%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

2 / 100 (2.00%)

4 / 373 (1.07%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

1 / 2

0 / 0

1 / 2

3 / 4

deaths causally related to treatment / all

0 / 0

Stenosis

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

2 / 69 (2.90%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

2 / 100 (2.00%)

5 / 373 (1.34%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 6

deaths causally related to treatment / all

0 / 0

Vascular device occlusion

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Reproductive system and breast disorders

Breast pain

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Genital prolapse

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Scrotal oedema

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pelvic pain

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Aspiration

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Asthma

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Chronic obstructive pulmonary disease

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

6 / 69 (8.70%)

4 / 42 (9.52%)

3 / 54 (5.56%)

2 / 30 (6.67%)

1 / 15 (6.67%)

6 / 69 (8.70%)

2 / 28 (7.14%)

0 / 3 (0.00%)

1 / 31 (3.23%)

1 / 32 (3.13%)

3 / 60 (5.00%)

7 / 100 (7.00%)

26 / 373 (6.97%)

occurrences causally related to treatment / all

1 / 6

0 / 4

0 / 3

0 / 1

0 / 9

0 / 3

0 / 0

0 / 1

0 / 4

0 / 10

1 / 31

deaths causally related to treatment / all

0 / 0

Cough

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Interstitial lung disease

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

2 / 2

deaths causally related to treatment / all

0 / 0

Organising pneumonia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 1

1 / 2

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

Pleural effusion

subjects affected / exposed

6 / 69 (8.70%)

1 / 42 (2.38%)

3 / 54 (5.56%)

0 / 30 (0.00%)

1 / 15 (6.67%)

2 / 69 (2.90%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

2 / 32 (6.25%)

2 / 60 (3.33%)

3 / 100 (3.00%)

16 / 373 (4.29%)

occurrences causally related to treatment / all

0 / 7

0 / 1

3 / 4

0 / 0

0 / 1

0 / 2

0 / 0

1 / 2

0 / 2

1 / 4

4 / 19

deaths causally related to treatment / all

0 / 0

Pleurisy

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pleuritic pain

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 69 (0.00%)

3 / 42 (7.14%)

1 / 54 (1.85%)

2 / 30 (6.67%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

7 / 373 (1.88%)

occurrences causally related to treatment / all

0 / 0

0 / 3

0 / 1

0 / 3

0 / 0

0 / 1

0 / 0

0 / 8

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed

1 / 69 (1.45%)

1 / 42 (2.38%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

4 / 373 (1.07%)

occurrences causally related to treatment / all

0 / 2

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 5

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

3 / 69 (4.35%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

2 / 60 (3.33%)

3 / 100 (3.00%)

6 / 373 (1.61%)

occurrences causally related to treatment / all

0 / 1

0 / 0

2 / 3

1 / 1

0 / 0

0 / 1

1 / 2

2 / 3

3 / 6

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

Pulmonary haemorrhage

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pulmonary venous thrombosis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Respiratory distress

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Respiratory failure

subjects affected / exposed

3 / 69 (4.35%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

1 / 100 (1.00%)

5 / 373 (1.34%)

occurrences causally related to treatment / all

0 / 3

0 / 0

0 / 1

0 / 0

0 / 1

0 / 5

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Psychiatric disorders

Agitation

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Confusional state

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Anxiety

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Disorientation

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Mental status changes

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Organic brain syndrome

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Investigations

Amylase increased

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Eastern Cooperative Oncology Group performance status worsened

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

General physical condition abnormal

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

1 / 3 (33.33%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

0 / 1

0 / 0

1 / 3

deaths causally related to treatment / all

0 / 0

Liver function test abnormal

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Platelet count decreased

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

SARS-CoV-2 test positive

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Troponin increased

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Accidental exposure to product

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Femur fracture

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Fracture displacement

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Lower limb fracture

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Radiation necrosis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Thoracic vertebral fracture

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Toxicity to various agents

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Congenital, familial and genetic disorders

Spinal muscular atrophy

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrial fibrillation

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Cardiac arrest

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 1

0 / 0

1 / 2

Cardiac failure

subjects affected / exposed

2 / 69 (2.90%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

4 / 373 (1.07%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 4

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Cardiopulmonary failure

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

Coronary artery disease

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Myocardial infarction

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Pericardial effusion

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Tachycardia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Supraventricular tachycardia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Aphasia

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cerebral ischaemia

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Cerebral mass effect

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cerebrovascular accident

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Epilepsy

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hemiparesis

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Neurological symptom

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

2 / 69 (2.90%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Paraplegia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Febrile neutropenia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Thrombocytopenia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

1 / 32 (3.13%)

1 / 60 (1.67%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

1 / 1

2 / 2

deaths causally related to treatment / all

0 / 0

Ear and labyrinth disorders

Hypoacusis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

2 / 2

deaths causally related to treatment / all

0 / 0

Vertigo

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

1 / 69 (1.45%)

2 / 42 (4.76%)

2 / 54 (3.70%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

6 / 373 (1.61%)

occurrences causally related to treatment / all

0 / 1

0 / 2

0 / 0

1 / 1

0 / 0

1 / 1

1 / 6

deaths causally related to treatment / all

0 / 0

Anal prolapse

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

3 / 3

deaths causally related to treatment / all

0 / 0

Constipation

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Duodenal stenosis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Dysphagia

subjects affected / exposed

2 / 69 (2.90%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 2

0 / 0

0 / 1

0 / 0

0 / 1

0 / 3

deaths causally related to treatment / all

0 / 0

Duodenitis

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

2 / 54 (3.70%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

3 / 69 (4.35%)

3 / 42 (7.14%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

7 / 373 (1.88%)

occurrences causally related to treatment / all

2 / 3

0 / 0

1 / 1

0 / 0

1 / 1

5 / 7

deaths causally related to treatment / all

0 / 0

Intestinal polyp

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Oesophageal stenosis

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pancreatitis acute

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

4 / 69 (5.80%)

2 / 42 (4.76%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

1 / 32 (3.13%)

1 / 60 (1.67%)

1 / 100 (1.00%)

9 / 373 (2.41%)

occurrences causally related to treatment / all

2 / 5

2 / 2

0 / 0

0 / 1

0 / 0

1 / 1

6 / 10

deaths causally related to treatment / all

0 / 0

Stomatitis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Hepatic function abnormal

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Drug-induced liver injury

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

1 / 60 (1.67%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

0 / 1

1 / 1

1 / 2

deaths causally related to treatment / all

0 / 0

Hepatitis

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

1 / 1

0 / 0

1 / 1

Hepatotoxicity

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Hyperbilirubinaemia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Skin and subcutaneous tissue disorders

Urticaria

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Calculus urinary

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Acute kidney injury

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Haematuria

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Renal failure

subjects affected / exposed

1 / 69 (1.45%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

1 / 1

0 / 0

2 / 2

deaths causally related to treatment / all

0 / 0

Renal infarct

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Urinary retention

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Endocrine disorders

Inappropriate antidiuretic hormone secretion

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Primary adrenal insufficiency

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthralgia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

1 / 15 (6.67%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

1 / 100 (1.00%)

4 / 373 (1.07%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 4

deaths causally related to treatment / all

0 / 0

Back pain

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Bone pain

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Muscular weakness

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

2 / 100 (2.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 3

deaths causally related to treatment / all

0 / 0

Musculoskeletal chest pain

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Osteolysis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Sacroiliitis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pain in extremity

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Infections and infestations

Bronchitis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

COVID-19

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

COVID-19 pneumonia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Device related infection

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

4 / 69 (5.80%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

4 / 100 (4.00%)

6 / 373 (1.61%)

occurrences causally related to treatment / all

0 / 1

0 / 0

2 / 4

0 / 1

0 / 0

0 / 1

2 / 4

2 / 6

deaths causally related to treatment / all

0 / 0

Erysipelas

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

2 / 60 (3.33%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Haemophilus infection

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Herpes zoster

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Infection

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 4

1 / 1

0 / 0

1 / 5

deaths causally related to treatment / all

0 / 0

Infectious pleural effusion

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

1 / 31 (3.23%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

deaths causally related to treatment / all

0 / 0

Influenza

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Lung abscess

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Medical device site infection

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pleural infection

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

7 / 69 (10.14%)

4 / 42 (9.52%)

3 / 54 (5.56%)

1 / 30 (3.33%)

0 / 15 (0.00%)

4 / 69 (5.80%)

0 / 28 (0.00%)

1 / 3 (33.33%)

2 / 31 (6.45%)

1 / 32 (3.13%)

1 / 60 (1.67%)

6 / 100 (6.00%)

23 / 373 (6.17%)

occurrences causally related to treatment / all

0 / 8

0 / 4

0 / 3

0 / 1

0 / 0

1 / 4

0 / 0

0 / 1

0 / 3

0 / 1

1 / 7

1 / 25

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

Pneumonia influenzal

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pneumonia bacterial

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 1

0 / 0

0 / 1

Pneumonia aspiration

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

1 / 60 (1.67%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

2 / 69 (2.90%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

2 / 100 (2.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Respiratory tract infection

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

2 / 54 (3.70%)

2 / 30 (6.67%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

5 / 373 (1.34%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 2

0 / 0

0 / 5

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

Septic shock

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

Urinary tract infection

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

2 / 30 (6.67%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Urosepsis

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

1 / 30 (3.33%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Decreased appetite

subjects affected / exposed

0 / 69 (0.00%)

1 / 42 (2.38%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

1 / 69 (1.45%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

1 / 100 (1.00%)

2 / 373 (0.54%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 1

2 / 2

deaths causally related to treatment / all

0 / 0

Hypokalaemia

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hyperkalaemia

subjects affected / exposed

1 / 69 (1.45%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

0 / 31 (0.00%)

0 / 32 (0.00%)

0 / 60 (0.00%)

0 / 100 (0.00%)

1 / 373 (0.27%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Dehydration

subjects affected / exposed

0 / 69 (0.00%)

0 / 42 (0.00%)

0 / 54 (0.00%)

0 / 30 (0.00%)

0 / 15 (0.00%)

0 / 69 (0.00%)

0 / 28 (0.00%)

0 / 3 (0.00%)

2 / 31 (6.45%)

1 / 32 (3.13%)

1 / 60 (1.67%)

2 / 100 (2.00%)

3 / 373 (0.80%)

occurrences causally related to treatment / all

0 / 0

2 / 2

0 / 1

2 / 2

2 / 3

deaths causally related to treatment / all

0 / 0

Hyponatraemia

subjects affected / exposed

2 / 69 (2.90%)

0 / 42 (0.00%)

1 / 54 (1.85%)

0 / 30 (0.00%)

1 / 15 (6.67%)

0 / 69 (0.00%)

1 / 28 (3.57%)

0 / 3 (0.00%)

0 / 31 (0.00%)

1 / 32 (3.13%)

2 / 60 (3.33%)

0 / 100 (0.00%)

6 / 373 (1.61%)

occurrences causally related to treatment / all

0 / 2

0 / 0

1 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 2

0 / 0

1 / 6

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Cohort 1a: On-treatment	Cohort 1b: On-treatment	Cohort 2: On-treatment	Cohort 3: On-treatment	Cohort 5a: On-treatment	Cohort 4: 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 5b + Cohort 7: On-treatment	Cohort 4 + Cohort 6.2: On-treatment	All patients: On-treatment
Total subjects affected by non serious adverse events
subjects affected / exposed	66 / 69 (95.65%)	41 / 42 (97.62%)	53 / 54 (98.15%)	28 / 30 (93.33%)	15 / 15 (100.00%)	66 / 69 (95.65%)	28 / 28 (100.00%)	3 / 3 (100.00%)	29 / 31 (93.55%)	31 / 32 (96.88%)	59 / 60 (98.33%)	95 / 100 (95.00%)	360 / 373 (96.51%)
Vascular disorders
Hypotension
subjects affected / exposed	4 / 69 (5.80%)	1 / 42 (2.38%)	2 / 54 (3.70%)	1 / 30 (3.33%)	0 / 15 (0.00%)	5 / 69 (7.25%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	5 / 32 (15.63%)	5 / 60 (8.33%)	6 / 100 (6.00%)	19 / 373 (5.09%)
occurrences all number	4	1	2	1	0	7	0	0	1	7	7	8	23
Embolism
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	1 / 32 (3.13%)	1 / 60 (1.67%)	2 / 100 (2.00%)	5 / 373 (1.34%)
occurrences all number	1	0	0	0	1	1	0	0	1	1	1	2	5
Hypertension
subjects affected / exposed	4 / 69 (5.80%)	0 / 42 (0.00%)	1 / 54 (1.85%)	1 / 30 (3.33%)	1 / 15 (6.67%)	2 / 69 (2.90%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	1 / 32 (3.13%)	2 / 60 (3.33%)	4 / 100 (4.00%)	13 / 373 (3.49%)
occurrences all number	4	0	1	1	1	2	2	0	2	1	3	4	14
Deep vein thrombosis
subjects affected / exposed	0 / 69 (0.00%)	2 / 42 (4.76%)	2 / 54 (3.70%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	2 / 60 (3.33%)	2 / 100 (2.00%)	9 / 373 (2.41%)
occurrences all number	0	2	2	0	1	1	0	0	1	2	2	2	9
Superficial vein thrombosis
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	2 / 60 (3.33%)	0 / 100 (0.00%)	2 / 373 (0.54%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	2	0	2
General disorders and administration site conditions
Generalised oedema
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	3 / 60 (5.00%)	2 / 100 (2.00%)	6 / 373 (1.61%)
occurrences all number	0	1	0	0	0	1	1	0	1	4	5	2	8
Fatigue
subjects affected / exposed	11 / 69 (15.94%)	10 / 42 (23.81%)	16 / 54 (29.63%)	6 / 30 (20.00%)	2 / 15 (13.33%)	19 / 69 (27.54%)	4 / 28 (14.29%)	1 / 3 (33.33%)	11 / 31 (35.48%)	6 / 32 (18.75%)	10 / 60 (16.67%)	30 / 100 (30.00%)	86 / 373 (23.06%)
occurrences all number	11	10	18	6	5	22	5	1	12	6	11	34	96
Face oedema
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	4 / 69 (5.80%)	2 / 28 (7.14%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	2 / 60 (3.33%)	5 / 100 (5.00%)	9 / 373 (2.41%)
occurrences all number	2	0	1	0	0	4	2	0	1	0	2	5	10
Chest discomfort
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	1 / 60 (1.67%)	1 / 100 (1.00%)	6 / 373 (1.61%)
occurrences all number	1	1	1	0	1	1	1	0	0	0	1	1	6
Asthenia
subjects affected / exposed	6 / 69 (8.70%)	8 / 42 (19.05%)	11 / 54 (20.37%)	3 / 30 (10.00%)	2 / 15 (13.33%)	6 / 69 (8.70%)	4 / 28 (14.29%)	0 / 3 (0.00%)	3 / 31 (9.68%)	6 / 32 (18.75%)	10 / 60 (16.67%)	9 / 100 (9.00%)	49 / 373 (13.14%)
occurrences all number	7	9	11	3	3	11	4	0	4	6	10	15	58
Malaise
subjects affected / exposed	2 / 69 (2.90%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	3 / 69 (4.35%)	2 / 28 (7.14%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	2 / 60 (3.33%)	4 / 100 (4.00%)	9 / 373 (2.41%)
occurrences all number	2	0	1	0	0	4	2	0	1	0	2	5	10
Pyrexia
subjects affected / exposed	8 / 69 (11.59%)	7 / 42 (16.67%)	8 / 54 (14.81%)	5 / 30 (16.67%)	3 / 15 (20.00%)	9 / 69 (13.04%)	2 / 28 (7.14%)	1 / 3 (33.33%)	2 / 31 (6.45%)	4 / 32 (12.50%)	6 / 60 (10.00%)	11 / 100 (11.00%)	49 / 373 (13.14%)
occurrences all number	11	9	9	9	4	11	2	1	2	8	10	13	66
Peripheral swelling
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	1 / 54 (1.85%)	1 / 30 (3.33%)	1 / 15 (6.67%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	3 / 32 (9.38%)	4 / 60 (6.67%)	1 / 100 (1.00%)	10 / 373 (2.68%)
occurrences all number	2	3	2	1	1	1	1	0	0	5	6	1	16
Non-cardiac chest pain
subjects affected / exposed	8 / 69 (11.59%)	5 / 42 (11.90%)	7 / 54 (12.96%)	1 / 30 (3.33%)	3 / 15 (20.00%)	4 / 69 (5.80%)	1 / 28 (3.57%)	0 / 3 (0.00%)	3 / 31 (9.68%)	0 / 32 (0.00%)	1 / 60 (1.67%)	7 / 100 (7.00%)	32 / 373 (8.58%)
occurrences all number	10	6	8	1	3	6	1	0	3	0	1	9	38
Oedema
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	4 / 28 (14.29%)	0 / 3 (0.00%)	0 / 31 (0.00%)	3 / 32 (9.38%)	7 / 60 (11.67%)	0 / 100 (0.00%)	8 / 373 (2.14%)
occurrences all number	1	0	0	0	0	0	5	0	0	3	8	0	9
Oedema peripheral
subjects affected / exposed	34 / 69 (49.28%)	18 / 42 (42.86%)	24 / 54 (44.44%)	11 / 30 (36.67%)	10 / 15 (66.67%)	38 / 69 (55.07%)	21 / 28 (75.00%)	1 / 3 (33.33%)	23 / 31 (74.19%)	23 / 32 (71.88%)	44 / 60 (73.33%)	61 / 100 (61.00%)	203 / 373 (54.42%)
occurrences all number	53	28	37	12	15	71	45	1	46	35	80	117	343
Pain
subjects affected / exposed	4 / 69 (5.80%)	0 / 42 (0.00%)	1 / 54 (1.85%)	1 / 30 (3.33%)	0 / 15 (0.00%)	2 / 69 (2.90%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	1 / 60 (1.67%)	2 / 100 (2.00%)	9 / 373 (2.41%)
occurrences all number	4	0	1	1	0	2	0	0	0	1	1	2	9
Immune system disorders
Contrast media allergy
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	2 / 28 (7.14%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	3 / 60 (5.00%)	0 / 100 (0.00%)	3 / 373 (0.80%)
occurrences all number	0	0	0	0	0	0	2	0	0	2	4	0	4
Reproductive system and breast disorders
Oedema genital
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	2 / 28 (7.14%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	3 / 60 (5.00%)	0 / 100 (0.00%)	3 / 373 (0.80%)
occurrences all number	0	0	0	0	0	0	2	0	0	1	3	0	3
Breast swelling
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Breast pain
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	2 / 28 (7.14%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	2 / 60 (3.33%)	1 / 100 (1.00%)	3 / 373 (0.80%)
occurrences all number	0	0	0	0	0	0	2	0	1	0	2	1	3
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	9 / 69 (13.04%)	9 / 42 (21.43%)	9 / 54 (16.67%)	4 / 30 (13.33%)	2 / 15 (13.33%)	11 / 69 (15.94%)	7 / 28 (25.00%)	0 / 3 (0.00%)	7 / 31 (22.58%)	3 / 32 (9.38%)	10 / 60 (16.67%)	18 / 100 (18.00%)	61 / 373 (16.35%)
occurrences all number	14	10	9	4	2	13	9	0	8	5	14	21	74
Dysphonia
subjects affected / exposed	4 / 69 (5.80%)	1 / 42 (2.38%)	0 / 54 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	2 / 69 (2.90%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	0 / 32 (0.00%)	1 / 60 (1.67%)	4 / 100 (4.00%)	11 / 373 (2.95%)
occurrences all number	4	1	0	1	0	3	1	0	2	0	1	5	12
Interstitial lung disease
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	1 / 100 (1.00%)	2 / 373 (0.54%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	1	2
Hypoxia
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	2 / 69 (2.90%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	0 / 32 (0.00%)	1 / 60 (1.67%)	4 / 100 (4.00%)	5 / 373 (1.34%)
occurrences all number	0	0	0	0	0	2	2	0	2	0	2	4	6
Haemoptysis
subjects affected / exposed	3 / 69 (4.35%)	3 / 42 (7.14%)	3 / 54 (5.56%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	1 / 3 (33.33%)	3 / 31 (9.68%)	1 / 32 (3.13%)	2 / 60 (3.33%)	4 / 100 (4.00%)	16 / 373 (4.29%)
occurrences all number	3	3	3	0	0	1	1	1	5	1	2	6	18
Epistaxis
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	1 / 30 (3.33%)	2 / 15 (13.33%)	3 / 69 (4.35%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	3 / 32 (9.38%)	4 / 60 (6.67%)	3 / 100 (3.00%)	11 / 373 (2.95%)
occurrences all number	0	1	0	1	2	3	1	0	0	3	4	3	11
Emphysema
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Dyspnoea exertional
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	1 / 54 (1.85%)	1 / 30 (3.33%)	1 / 15 (6.67%)	3 / 69 (4.35%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	2 / 60 (3.33%)	3 / 100 (3.00%)	8 / 373 (2.14%)
occurrences all number	0	0	1	1	1	4	1	0	0	1	2	4	9
Dyspnoea
subjects affected / exposed	11 / 69 (15.94%)	15 / 42 (35.71%)	11 / 54 (20.37%)	5 / 30 (16.67%)	5 / 15 (33.33%)	16 / 69 (23.19%)	6 / 28 (21.43%)	2 / 3 (66.67%)	6 / 31 (19.35%)	6 / 32 (18.75%)	12 / 60 (20.00%)	22 / 100 (22.00%)	83 / 373 (22.25%)
occurrences all number	12	17	15	8	5	17	8	2	6	6	14	23	96
Rhinitis allergic
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	1 / 28 (3.57%)	0 / 3 (0.00%)	3 / 31 (9.68%)	1 / 32 (3.13%)	2 / 60 (3.33%)	3 / 100 (3.00%)	5 / 373 (1.34%)
occurrences all number	0	0	0	0	0	0	1	0	4	1	2	4	6
Pulmonary embolism
subjects affected / exposed	1 / 69 (1.45%)	4 / 42 (9.52%)	2 / 54 (3.70%)	0 / 30 (0.00%)	2 / 15 (13.33%)	2 / 69 (2.90%)	2 / 28 (7.14%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	4 / 60 (6.67%)	2 / 100 (2.00%)	15 / 373 (4.02%)
occurrences all number	2	4	2	0	2	2	2	0	0	2	4	2	16
Productive cough
subjects affected / exposed	3 / 69 (4.35%)	0 / 42 (0.00%)	2 / 54 (3.70%)	4 / 30 (13.33%)	0 / 15 (0.00%)	4 / 69 (5.80%)	3 / 28 (10.71%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	5 / 60 (8.33%)	5 / 100 (5.00%)	19 / 373 (5.09%)
occurrences all number	3	0	2	4	0	4	5	0	1	2	7	5	21
Pneumonitis
subjects affected / exposed	3 / 69 (4.35%)	0 / 42 (0.00%)	0 / 54 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	4 / 69 (5.80%)	1 / 28 (3.57%)	1 / 3 (33.33%)	0 / 31 (0.00%)	1 / 32 (3.13%)	2 / 60 (3.33%)	4 / 100 (4.00%)	11 / 373 (2.95%)
occurrences all number	4	0	0	1	0	6	1	1	0	2	3	6	15
Pleurisy
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	3 / 60 (5.00%)	2 / 100 (2.00%)	5 / 373 (1.34%)
occurrences all number	0	0	0	0	0	1	1	0	2	3	4	3	7
Pleural effusion
subjects affected / exposed	3 / 69 (4.35%)	4 / 42 (9.52%)	3 / 54 (5.56%)	0 / 30 (0.00%)	0 / 15 (0.00%)	3 / 69 (4.35%)	0 / 28 (0.00%)	0 / 3 (0.00%)	2 / 31 (6.45%)	2 / 32 (6.25%)	2 / 60 (3.33%)	5 / 100 (5.00%)	17 / 373 (4.56%)
occurrences all number	3	9	4	0	0	4	0	0	2	2	2	6	24
Oropharyngeal pain
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	0 / 28 (0.00%)	1 / 3 (33.33%)	3 / 31 (9.68%)	0 / 32 (0.00%)	0 / 60 (0.00%)	4 / 100 (4.00%)	8 / 373 (2.14%)
occurrences all number	1	1	1	0	0	1	0	1	3	0	0	4	8
Rhinorrhoea
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	0 / 54 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	2 / 69 (2.90%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	1 / 32 (3.13%)	2 / 60 (3.33%)	4 / 100 (4.00%)	9 / 373 (2.41%)
occurrences all number	1	1	0	1	0	2	1	0	4	1	2	6	11
Psychiatric disorders
Insomnia
subjects affected / exposed	7 / 69 (10.14%)	3 / 42 (7.14%)	3 / 54 (5.56%)	1 / 30 (3.33%)	0 / 15 (0.00%)	6 / 69 (8.70%)	5 / 28 (17.86%)	0 / 3 (0.00%)	3 / 31 (9.68%)	6 / 32 (18.75%)	11 / 60 (18.33%)	9 / 100 (9.00%)	34 / 373 (9.12%)
occurrences all number	7	3	3	1	0	7	5	0	3	6	11	10	35
Dysphoria
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Depression
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	2 / 54 (3.70%)	0 / 30 (0.00%)	0 / 15 (0.00%)	3 / 69 (4.35%)	0 / 28 (0.00%)	0 / 3 (0.00%)	3 / 31 (9.68%)	2 / 32 (6.25%)	2 / 60 (3.33%)	6 / 100 (6.00%)	12 / 373 (3.22%)
occurrences all number	1	1	2	0	0	3	0	0	3	2	2	6	12
Confusional state
subjects affected / exposed	2 / 69 (2.90%)	0 / 42 (0.00%)	0 / 54 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)	0 / 69 (0.00%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	1 / 60 (1.67%)	0 / 100 (0.00%)	5 / 373 (1.34%)
occurrences all number	2	0	0	1	1	0	1	0	0	0	1	0	5
Anxiety
subjects affected / exposed	0 / 69 (0.00%)	3 / 42 (7.14%)	4 / 54 (7.41%)	0 / 30 (0.00%)	1 / 15 (6.67%)	3 / 69 (4.35%)	2 / 28 (7.14%)	0 / 3 (0.00%)	1 / 31 (3.23%)	1 / 32 (3.13%)	3 / 60 (5.00%)	4 / 100 (4.00%)	15 / 373 (4.02%)
occurrences all number	0	3	4	0	1	3	2	0	1	1	3	4	15
Sleep disorder
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	2 / 15 (13.33%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	5 / 373 (1.34%)
occurrences all number	1	1	1	0	2	0	0	0	0	0	0	0	5
Investigations
Amylase increased
subjects affected / exposed	9 / 69 (13.04%)	3 / 42 (7.14%)	2 / 54 (3.70%)	1 / 30 (3.33%)	3 / 15 (20.00%)	7 / 69 (10.14%)	2 / 28 (7.14%)	0 / 3 (0.00%)	4 / 31 (12.90%)	5 / 32 (15.63%)	7 / 60 (11.67%)	11 / 100 (11.00%)	36 / 373 (9.65%)
occurrences all number	15	4	2	1	3	10	2	0	7	5	7	17	49
Alanine aminotransferase increased
subjects affected / exposed	13 / 69 (18.84%)	4 / 42 (9.52%)	5 / 54 (9.26%)	3 / 30 (10.00%)	5 / 15 (33.33%)	9 / 69 (13.04%)	4 / 28 (14.29%)	0 / 3 (0.00%)	7 / 31 (22.58%)	3 / 32 (9.38%)	7 / 60 (11.67%)	16 / 100 (16.00%)	53 / 373 (14.21%)
occurrences all number	17	4	5	3	7	9	5	0	9	6	11	18	65
Aspartate aminotransferase increased
subjects affected / exposed	11 / 69 (15.94%)	2 / 42 (4.76%)	4 / 54 (7.41%)	3 / 30 (10.00%)	5 / 15 (33.33%)	6 / 69 (8.70%)	2 / 28 (7.14%)	0 / 3 (0.00%)	4 / 31 (12.90%)	2 / 32 (6.25%)	4 / 60 (6.67%)	10 / 100 (10.00%)	39 / 373 (10.46%)
occurrences all number	14	3	5	3	6	8	2	0	5	3	5	13	49
Blood urine present
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Blood creatinine increased
subjects affected / exposed	16 / 69 (23.19%)	8 / 42 (19.05%)	14 / 54 (25.93%)	5 / 30 (16.67%)	3 / 15 (20.00%)	24 / 69 (34.78%)	10 / 28 (35.71%)	1 / 3 (33.33%)	10 / 31 (32.26%)	12 / 32 (37.50%)	22 / 60 (36.67%)	34 / 100 (34.00%)	103 / 373 (27.61%)
occurrences all number	55	11	26	9	7	55	13	3	15	44	57	70	238
Blood bilirubin increased
subjects affected / exposed	3 / 69 (4.35%)	2 / 42 (4.76%)	1 / 54 (1.85%)	1 / 30 (3.33%)	0 / 15 (0.00%)	1 / 69 (1.45%)	2 / 28 (7.14%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	4 / 60 (6.67%)	2 / 100 (2.00%)	13 / 373 (3.49%)
occurrences all number	11	2	2	1	0	1	4	0	1	2	6	2	24
Blood alkaline phosphatase increased
subjects affected / exposed	8 / 69 (11.59%)	1 / 42 (2.38%)	3 / 54 (5.56%)	0 / 30 (0.00%)	1 / 15 (6.67%)	5 / 69 (7.25%)	1 / 28 (3.57%)	0 / 3 (0.00%)	3 / 31 (9.68%)	3 / 32 (9.38%)	4 / 60 (6.67%)	8 / 100 (8.00%)	25 / 373 (6.70%)
occurrences all number	9	1	3	0	1	6	1	0	4	3	4	10	28
Blood albumin decreased
subjects affected / exposed	3 / 69 (4.35%)	0 / 42 (0.00%)	1 / 54 (1.85%)	1 / 30 (3.33%)	1 / 15 (6.67%)	5 / 69 (7.25%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	2 / 60 (3.33%)	5 / 100 (5.00%)	13 / 373 (3.49%)
occurrences all number	3	0	2	1	1	8	0	0	0	2	2	8	17
Liver function test abnormal
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	2 / 373 (0.54%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	2
Lipase increased
subjects affected / exposed	5 / 69 (7.25%)	4 / 42 (9.52%)	1 / 54 (1.85%)	4 / 30 (13.33%)	1 / 15 (6.67%)	7 / 69 (10.14%)	5 / 28 (17.86%)	0 / 3 (0.00%)	3 / 31 (9.68%)	7 / 32 (21.88%)	12 / 60 (20.00%)	10 / 100 (10.00%)	37 / 373 (9.92%)
occurrences all number	8	5	1	6	1	17	5	0	15	13	18	32	71
Gamma-glutamyltransferase increased
subjects affected / exposed	9 / 69 (13.04%)	2 / 42 (4.76%)	5 / 54 (9.26%)	0 / 30 (0.00%)	0 / 15 (0.00%)	3 / 69 (4.35%)	2 / 28 (7.14%)	0 / 3 (0.00%)	3 / 31 (9.68%)	0 / 32 (0.00%)	2 / 60 (3.33%)	6 / 100 (6.00%)	24 / 373 (6.43%)
occurrences all number	13	2	6	0	0	4	2	0	3	0	2	7	30
Eastern Cooperative Oncology Group performance status worsened
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
C-reactive protein increased
subjects affected / exposed	3 / 69 (4.35%)	2 / 42 (4.76%)	0 / 54 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	1 / 3 (33.33%)	0 / 31 (0.00%)	2 / 32 (6.25%)	2 / 60 (3.33%)	0 / 100 (0.00%)	9 / 373 (2.41%)
occurrences all number	3	2	0	2	0	0	0	1	0	2	2	0	10
Liver function test increased
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	2 / 60 (3.33%)	1 / 100 (1.00%)	4 / 373 (1.07%)
occurrences all number	0	0	0	0	1	1	1	0	0	1	2	1	4
Lymphocyte count decreased
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	3 / 60 (5.00%)	1 / 100 (1.00%)	5 / 373 (1.34%)
occurrences all number	0	0	2	0	0	1	1	0	0	5	6	1	9
Neutrophil count decreased
subjects affected / exposed	3 / 69 (4.35%)	0 / 42 (0.00%)	2 / 54 (3.70%)	1 / 30 (3.33%)	1 / 15 (6.67%)	2 / 69 (2.90%)	1 / 28 (3.57%)	0 / 3 (0.00%)	1 / 31 (3.23%)	3 / 32 (9.38%)	4 / 60 (6.67%)	3 / 100 (3.00%)	14 / 373 (3.75%)
occurrences all number	3	0	2	2	1	7	2	0	1	3	5	8	21
Platelet count decreased
subjects affected / exposed	3 / 69 (4.35%)	0 / 42 (0.00%)	3 / 54 (5.56%)	1 / 30 (3.33%)	1 / 15 (6.67%)	5 / 69 (7.25%)	1 / 28 (3.57%)	1 / 3 (33.33%)	1 / 31 (3.23%)	1 / 32 (3.13%)	2 / 60 (3.33%)	6 / 100 (6.00%)	17 / 373 (4.56%)
occurrences all number	8	0	3	1	1	14	2	2	2	1	3	16	34
Procalcitonin increased
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	1 / 3 (33.33%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	1
Protein total decreased
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	2 / 31 (6.45%)	1 / 32 (3.13%)	1 / 60 (1.67%)	2 / 100 (2.00%)	3 / 373 (0.80%)
occurrences all number	0	0	0	0	0	0	0	0	3	1	1	3	4
Weight decreased
subjects affected / exposed	7 / 69 (10.14%)	4 / 42 (9.52%)	2 / 54 (3.70%)	4 / 30 (13.33%)	3 / 15 (20.00%)	9 / 69 (13.04%)	4 / 28 (14.29%)	1 / 3 (33.33%)	1 / 31 (3.23%)	6 / 32 (18.75%)	10 / 60 (16.67%)	10 / 100 (10.00%)	41 / 373 (10.99%)
occurrences all number	7	4	2	4	3	11	4	2	1	6	10	12	44
Weight increased
subjects affected / exposed	7 / 69 (10.14%)	0 / 42 (0.00%)	2 / 54 (3.70%)	0 / 30 (0.00%)	1 / 15 (6.67%)	4 / 69 (5.80%)	3 / 28 (10.71%)	0 / 3 (0.00%)	2 / 31 (6.45%)	2 / 32 (6.25%)	5 / 60 (8.33%)	6 / 100 (6.00%)	21 / 373 (5.63%)
occurrences all number	7	0	2	0	2	4	3	0	2	2	5	6	22
White blood cell count decreased
subjects affected / exposed	2 / 69 (2.90%)	0 / 42 (0.00%)	1 / 54 (1.85%)	1 / 30 (3.33%)	1 / 15 (6.67%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	2 / 60 (3.33%)	1 / 100 (1.00%)	8 / 373 (2.14%)
occurrences all number	2	0	1	4	1	1	2	0	0	2	4	1	13
Injury, poisoning and procedural complications
Anastomotic ulcer
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Face injury
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Fall
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	2 / 69 (2.90%)	2 / 28 (7.14%)	0 / 3 (0.00%)	2 / 31 (6.45%)	2 / 32 (6.25%)	4 / 60 (6.67%)	4 / 100 (4.00%)	11 / 373 (2.95%)
occurrences all number	1	0	3	0	1	2	2	0	2	3	5	4	14
Head injury
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Limb injury
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	0 / 32 (0.00%)	1 / 60 (1.67%)	3 / 100 (3.00%)	4 / 373 (1.07%)
occurrences all number	0	0	0	0	0	1	1	0	2	0	1	3	4
Pelvic fracture
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	2 / 373 (0.54%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0	0	2
Spinal compression fracture
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	2 / 15 (13.33%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	3 / 373 (0.80%)
occurrences all number	1	0	0	0	2	0	0	0	0	0	0	0	3
Cardiac disorders
Tachycardia
subjects affected / exposed	0 / 69 (0.00%)	3 / 42 (7.14%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	2 / 69 (2.90%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	2 / 100 (2.00%)	5 / 373 (1.34%)
occurrences all number	0	4	0	0	0	2	0	0	0	0	0	2	6
Sinus bradycardia
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	4 / 69 (5.80%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	1 / 60 (1.67%)	4 / 100 (4.00%)	5 / 373 (1.34%)
occurrences all number	0	0	0	0	0	4	1	0	0	0	1	4	5
Palpitations
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	2 / 69 (2.90%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	3 / 60 (5.00%)	2 / 100 (2.00%)	9 / 373 (2.41%)
occurrences all number	1	1	1	0	2	2	2	0	0	2	4	2	11
Cardiac failure
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	2 / 60 (3.33%)	0 / 100 (0.00%)	3 / 373 (0.80%)
occurrences all number	0	1	0	0	0	0	0	0	0	2	2	0	3
Atrial fibrillation
subjects affected / exposed	2 / 69 (2.90%)	0 / 42 (0.00%)	2 / 54 (3.70%)	0 / 30 (0.00%)	1 / 15 (6.67%)	2 / 69 (2.90%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	1 / 60 (1.67%)	2 / 100 (2.00%)	8 / 373 (2.14%)
occurrences all number	2	0	3	0	1	2	0	0	0	1	1	2	9
Nervous system disorders
Disturbance in attention
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Dizziness
subjects affected / exposed	4 / 69 (5.80%)	5 / 42 (11.90%)	1 / 54 (1.85%)	2 / 30 (6.67%)	2 / 15 (13.33%)	9 / 69 (13.04%)	3 / 28 (10.71%)	1 / 3 (33.33%)	3 / 31 (9.68%)	4 / 32 (12.50%)	7 / 60 (11.67%)	12 / 100 (12.00%)	34 / 373 (9.12%)
occurrences all number	4	5	1	2	2	9	4	2	7	7	11	16	43
Paraesthesia
subjects affected / exposed	1 / 69 (1.45%)	3 / 42 (7.14%)	2 / 54 (3.70%)	0 / 30 (0.00%)	0 / 15 (0.00%)	3 / 69 (4.35%)	1 / 28 (3.57%)	0 / 3 (0.00%)	3 / 31 (9.68%)	2 / 32 (6.25%)	3 / 60 (5.00%)	6 / 100 (6.00%)	15 / 373 (4.02%)
occurrences all number	2	3	2	0	0	3	1	0	3	2	3	6	16
Neuropathy peripheral
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	2 / 69 (2.90%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	3 / 32 (9.38%)	3 / 60 (5.00%)	2 / 100 (2.00%)	6 / 373 (1.61%)
occurrences all number	1	0	0	0	0	2	0	0	0	3	3	2	6
Hypoaesthesia
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	0 / 54 (0.00%)	1 / 30 (3.33%)	1 / 15 (6.67%)	2 / 69 (2.90%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	2 / 100 (2.00%)	6 / 373 (1.61%)
occurrences all number	4	1	0	1	1	2	0	0	0	0	0	2	9
Headache
subjects affected / exposed	6 / 69 (8.70%)	4 / 42 (9.52%)	3 / 54 (5.56%)	2 / 30 (6.67%)	1 / 15 (6.67%)	9 / 69 (13.04%)	2 / 28 (7.14%)	0 / 3 (0.00%)	2 / 31 (6.45%)	1 / 32 (3.13%)	3 / 60 (5.00%)	11 / 100 (11.00%)	30 / 373 (8.04%)
occurrences all number	7	6	3	2	1	9	2	0	3	1	3	12	34
Dysgeusia
subjects affected / exposed	3 / 69 (4.35%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	3 / 60 (5.00%)	0 / 100 (0.00%)	6 / 373 (1.61%)
occurrences all number	3	0	0	0	0	0	1	0	0	2	3	0	6
Dysarthria
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	0 / 60 (0.00%)	1 / 100 (1.00%)	2 / 373 (0.54%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	1	2
Somnolence
subjects affected / exposed	2 / 69 (2.90%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	1 / 100 (1.00%)	5 / 373 (1.34%)
occurrences all number	2	0	1	0	1	1	0	0	0	0	0	1	5
Syncope
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	2 / 28 (7.14%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	2 / 60 (3.33%)	1 / 100 (1.00%)	5 / 373 (1.34%)
occurrences all number	0	1	1	0	0	1	2	0	0	0	2	1	5
Taste disorder
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	1 / 32 (3.13%)	1 / 60 (1.67%)	2 / 100 (2.00%)	5 / 373 (1.34%)
occurrences all number	0	0	1	0	1	1	0	0	1	1	1	2	5
Tremor
subjects affected / exposed	0 / 69 (0.00%)	2 / 42 (4.76%)	2 / 54 (3.70%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	2 / 31 (6.45%)	0 / 32 (0.00%)	0 / 60 (0.00%)	2 / 100 (2.00%)	6 / 373 (1.61%)
occurrences all number	0	3	2	0	0	0	0	0	2	0	0	2	7
Blood and lymphatic system disorders
Neutropenia
subjects affected / exposed	2 / 69 (2.90%)	0 / 42 (0.00%)	1 / 54 (1.85%)	1 / 30 (3.33%)	1 / 15 (6.67%)	1 / 69 (1.45%)	2 / 28 (7.14%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	2 / 60 (3.33%)	2 / 100 (2.00%)	9 / 373 (2.41%)
occurrences all number	4	0	1	1	1	3	2	0	1	0	2	4	13
Thrombocytopenia
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	2 / 69 (2.90%)	0 / 28 (0.00%)	0 / 3 (0.00%)	3 / 31 (9.68%)	3 / 32 (9.38%)	3 / 60 (5.00%)	5 / 100 (5.00%)	9 / 373 (2.41%)
occurrences all number	1	0	0	0	0	4	0	0	8	3	3	12	16
Anaemia
subjects affected / exposed	5 / 69 (7.25%)	2 / 42 (4.76%)	5 / 54 (9.26%)	6 / 30 (20.00%)	1 / 15 (6.67%)	8 / 69 (11.59%)	2 / 28 (7.14%)	0 / 3 (0.00%)	4 / 31 (12.90%)	2 / 32 (6.25%)	4 / 60 (6.67%)	12 / 100 (12.00%)	35 / 373 (9.38%)
occurrences all number	5	2	8	10	1	8	2	0	5	2	4	13	43
Leukopenia
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	2 / 54 (3.70%)	1 / 30 (3.33%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	0 / 60 (0.00%)	1 / 100 (1.00%)	6 / 373 (1.61%)
occurrences all number	2	0	2	1	1	0	0	0	1	0	0	1	7
Lymphopenia
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	1 / 54 (1.85%)	2 / 30 (6.67%)	0 / 15 (0.00%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	0 / 60 (0.00%)	2 / 100 (2.00%)	5 / 373 (1.34%)
occurrences all number	0	0	1	2	0	1	0	0	1	0	0	2	5
Ear and labyrinth disorders
Hypoacusis
subjects affected / exposed	2 / 69 (2.90%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	3 / 69 (4.35%)	2 / 28 (7.14%)	0 / 3 (0.00%)	0 / 31 (0.00%)	5 / 32 (15.63%)	7 / 60 (11.67%)	3 / 100 (3.00%)	14 / 373 (3.75%)
occurrences all number	2	1	1	0	0	3	2	0	0	5	7	3	14
Tinnitus
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	3 / 28 (10.71%)	0 / 3 (0.00%)	3 / 31 (9.68%)	1 / 32 (3.13%)	4 / 60 (6.67%)	3 / 100 (3.00%)	8 / 373 (2.14%)
occurrences all number	1	0	0	0	0	0	3	0	3	1	4	3	8
Vertigo
subjects affected / exposed	2 / 69 (2.90%)	2 / 42 (4.76%)	2 / 54 (3.70%)	2 / 30 (6.67%)	0 / 15 (0.00%)	5 / 69 (7.25%)	1 / 28 (3.57%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	1 / 60 (1.67%)	6 / 100 (6.00%)	15 / 373 (4.02%)
occurrences all number	2	2	2	2	0	5	1	0	3	0	1	8	17
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	2 / 69 (2.90%)	3 / 42 (7.14%)	7 / 54 (12.96%)	1 / 30 (3.33%)	0 / 15 (0.00%)	3 / 69 (4.35%)	3 / 28 (10.71%)	0 / 3 (0.00%)	1 / 31 (3.23%)	3 / 32 (9.38%)	6 / 60 (10.00%)	4 / 100 (4.00%)	23 / 373 (6.17%)
occurrences all number	2	4	8	1	0	7	4	0	1	3	7	8	30
Abdominal discomfort
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	2 / 69 (2.90%)	0 / 28 (0.00%)	1 / 3 (33.33%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	2 / 100 (2.00%)	5 / 373 (1.34%)
occurrences all number	1	1	0	0	0	2	0	1	0	0	0	2	5
Abdominal pain upper
subjects affected / exposed	4 / 69 (5.80%)	4 / 42 (9.52%)	2 / 54 (3.70%)	2 / 30 (6.67%)	0 / 15 (0.00%)	5 / 69 (7.25%)	5 / 28 (17.86%)	0 / 3 (0.00%)	2 / 31 (6.45%)	3 / 32 (9.38%)	8 / 60 (13.33%)	7 / 100 (7.00%)	27 / 373 (7.24%)
occurrences all number	4	6	2	2	0	6	5	0	2	3	8	8	30
Abnormal faeces
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Nausea
subjects affected / exposed	32 / 69 (46.38%)	16 / 42 (38.10%)	24 / 54 (44.44%)	15 / 30 (50.00%)	9 / 15 (60.00%)	32 / 69 (46.38%)	13 / 28 (46.43%)	2 / 3 (66.67%)	12 / 31 (38.71%)	15 / 32 (46.88%)	28 / 60 (46.67%)	44 / 100 (44.00%)	170 / 373 (45.58%)
occurrences all number	42	21	26	18	12	48	19	2	16	19	38	64	223
Gastrooesophageal reflux disease
subjects affected / exposed	3 / 69 (4.35%)	1 / 42 (2.38%)	3 / 54 (5.56%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	3 / 60 (5.00%)	2 / 100 (2.00%)	12 / 373 (3.22%)
occurrences all number	3	1	3	0	0	1	1	0	2	2	3	3	13
Dysphagia
subjects affected / exposed	2 / 69 (2.90%)	4 / 42 (9.52%)	6 / 54 (11.11%)	1 / 30 (3.33%)	2 / 15 (13.33%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	1 / 60 (1.67%)	1 / 100 (1.00%)	17 / 373 (4.56%)
occurrences all number	2	4	7	1	2	1	0	0	0	1	1	1	18
Dyspepsia
subjects affected / exposed	4 / 69 (5.80%)	3 / 42 (7.14%)	4 / 54 (7.41%)	3 / 30 (10.00%)	0 / 15 (0.00%)	6 / 69 (8.70%)	2 / 28 (7.14%)	1 / 3 (33.33%)	1 / 31 (3.23%)	2 / 32 (6.25%)	4 / 60 (6.67%)	7 / 100 (7.00%)	26 / 373 (6.97%)
occurrences all number	4	3	4	4	0	6	2	1	1	2	4	7	27
Dry mouth
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	2 / 30 (6.67%)	0 / 15 (0.00%)	0 / 69 (0.00%)	1 / 28 (3.57%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	1 / 60 (1.67%)	1 / 100 (1.00%)	5 / 373 (1.34%)
occurrences all number	0	1	0	2	0	0	1	0	1	0	1	1	5
Diarrhoea
subjects affected / exposed	18 / 69 (26.09%)	6 / 42 (14.29%)	7 / 54 (12.96%)	8 / 30 (26.67%)	4 / 15 (26.67%)	13 / 69 (18.84%)	5 / 28 (17.86%)	0 / 3 (0.00%)	5 / 31 (16.13%)	4 / 32 (12.50%)	9 / 60 (15.00%)	18 / 100 (18.00%)	70 / 373 (18.77%)
occurrences all number	24	8	12	8	4	16	7	0	6	7	14	22	92
Constipation
subjects affected / exposed	16 / 69 (23.19%)	9 / 42 (21.43%)	10 / 54 (18.52%)	7 / 30 (23.33%)	6 / 15 (40.00%)	9 / 69 (13.04%)	5 / 28 (17.86%)	1 / 3 (33.33%)	3 / 31 (9.68%)	3 / 32 (9.38%)	8 / 60 (13.33%)	12 / 100 (12.00%)	69 / 373 (18.50%)
occurrences all number	16	10	10	8	6	11	5	2	3	3	8	14	74
Vomiting
subjects affected / exposed	22 / 69 (31.88%)	14 / 42 (33.33%)	12 / 54 (22.22%)	9 / 30 (30.00%)	4 / 15 (26.67%)	19 / 69 (27.54%)	7 / 28 (25.00%)	1 / 3 (33.33%)	8 / 31 (25.81%)	6 / 32 (18.75%)	13 / 60 (21.67%)	27 / 100 (27.00%)	102 / 373 (27.35%)
occurrences all number	34	16	17	13	5	38	9	1	8	15	24	46	156
Stomatitis
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	3 / 54 (5.56%)	0 / 30 (0.00%)	1 / 15 (6.67%)	3 / 69 (4.35%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	2 / 60 (3.33%)	4 / 100 (4.00%)	11 / 373 (2.95%)
occurrences all number	1	0	3	0	1	3	0	0	1	3	3	4	12
Hepatobiliary disorders
Hepatic steatosis
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	0 / 60 (0.00%)	1 / 100 (1.00%)	2 / 373 (0.54%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	1	2
Skin and subcutaneous tissue disorders
Dry skin
subjects affected / exposed	9 / 69 (13.04%)	1 / 42 (2.38%)	2 / 54 (3.70%)	1 / 30 (3.33%)	2 / 15 (13.33%)	2 / 69 (2.90%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	1 / 32 (3.13%)	1 / 60 (1.67%)	3 / 100 (3.00%)	19 / 373 (5.09%)
occurrences all number	9	2	2	1	3	2	0	0	1	1	1	3	21
Eczema
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	0 / 32 (0.00%)	1 / 60 (1.67%)	3 / 100 (3.00%)	4 / 373 (1.07%)
occurrences all number	0	0	0	0	0	1	1	0	2	0	1	3	4
Pruritus
subjects affected / exposed	7 / 69 (10.14%)	6 / 42 (14.29%)	3 / 54 (5.56%)	0 / 30 (0.00%)	2 / 15 (13.33%)	10 / 69 (14.49%)	2 / 28 (7.14%)	0 / 3 (0.00%)	3 / 31 (9.68%)	2 / 32 (6.25%)	4 / 60 (6.67%)	13 / 100 (13.00%)	35 / 373 (9.38%)
occurrences all number	7	6	4	0	2	12	2	0	5	5	7	17	43
Pruritus allergic
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Rash
subjects affected / exposed	3 / 69 (4.35%)	1 / 42 (2.38%)	4 / 54 (7.41%)	1 / 30 (3.33%)	2 / 15 (13.33%)	6 / 69 (8.70%)	0 / 28 (0.00%)	0 / 3 (0.00%)	4 / 31 (12.90%)	3 / 32 (9.38%)	3 / 60 (5.00%)	10 / 100 (10.00%)	24 / 373 (6.43%)
occurrences all number	3	2	4	1	2	6	0	0	4	3	3	10	25
Rash maculo-papular
subjects affected / exposed	2 / 69 (2.90%)	0 / 42 (0.00%)	2 / 54 (3.70%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	2 / 31 (6.45%)	0 / 32 (0.00%)	0 / 60 (0.00%)	2 / 100 (2.00%)	6 / 373 (1.61%)
occurrences all number	2	0	2	0	0	0	0	0	2	0	0	2	6
Alopecia
subjects affected / exposed	0 / 69 (0.00%)	3 / 42 (7.14%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	3 / 32 (9.38%)	4 / 60 (6.67%)	2 / 100 (2.00%)	10 / 373 (2.68%)
occurrences all number	0	3	0	0	1	0	1	0	2	3	4	2	10
Dermatitis acneiform
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	2 / 69 (2.90%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	2 / 60 (3.33%)	3 / 100 (3.00%)	7 / 373 (1.88%)
occurrences all number	1	0	1	0	0	3	0	0	2	2	2	5	9
Skin induration
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	0 / 60 (0.00%)	1 / 100 (1.00%)	2 / 373 (0.54%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	1	2
Skin lesion
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	2 / 60 (3.33%)	1 / 100 (1.00%)	4 / 373 (1.07%)
occurrences all number	0	1	0	0	0	1	0	0	0	2	2	1	4
Stasis dermatitis
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Renal and urinary disorders
Renal failure
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	3 / 373 (0.80%)
occurrences all number	1	1	0	0	1	0	0	0	0	0	0	0	3
Dysuria
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	0 / 28 (0.00%)	1 / 3 (33.33%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	1 / 100 (1.00%)	4 / 373 (1.07%)
occurrences all number	1	0	2	0	0	1	0	1	0	0	0	1	5
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	1 / 69 (1.45%)	3 / 42 (7.14%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	2 / 60 (3.33%)	1 / 100 (1.00%)	7 / 373 (1.88%)
occurrences all number	1	4	0	0	0	1	0	0	0	2	2	1	8
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	6 / 69 (8.70%)	3 / 42 (7.14%)	7 / 54 (12.96%)	0 / 30 (0.00%)	3 / 15 (20.00%)	8 / 69 (11.59%)	7 / 28 (25.00%)	1 / 3 (33.33%)	2 / 31 (6.45%)	2 / 32 (6.25%)	9 / 60 (15.00%)	10 / 100 (10.00%)	39 / 373 (10.46%)
occurrences all number	7	3	12	0	3	11	7	1	3	2	9	14	49
Muscle spasms
subjects affected / exposed	4 / 69 (5.80%)	6 / 42 (14.29%)	3 / 54 (5.56%)	1 / 30 (3.33%)	3 / 15 (20.00%)	1 / 69 (1.45%)	3 / 28 (10.71%)	0 / 3 (0.00%)	2 / 31 (6.45%)	3 / 32 (9.38%)	6 / 60 (10.00%)	3 / 100 (3.00%)	26 / 373 (6.97%)
occurrences all number	4	7	3	1	3	1	4	0	3	3	7	4	29
Joint swelling
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	2 / 28 (7.14%)	1 / 3 (33.33%)	1 / 31 (3.23%)	0 / 32 (0.00%)	2 / 60 (3.33%)	1 / 100 (1.00%)	6 / 373 (1.61%)
occurrences all number	0	1	0	0	1	0	2	1	1	0	2	1	6
Flank pain
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	1 / 3 (33.33%)	1 / 31 (3.23%)	0 / 32 (0.00%)	1 / 60 (1.67%)	2 / 100 (2.00%)	5 / 373 (1.34%)
occurrences all number	0	1	0	0	0	1	1	1	1	0	1	2	5
Back pain
subjects affected / exposed	8 / 69 (11.59%)	7 / 42 (16.67%)	10 / 54 (18.52%)	2 / 30 (6.67%)	2 / 15 (13.33%)	11 / 69 (15.94%)	4 / 28 (14.29%)	1 / 3 (33.33%)	11 / 31 (35.48%)	7 / 32 (21.88%)	11 / 60 (18.33%)	22 / 100 (22.00%)	63 / 373 (16.89%)
occurrences all number	8	7	10	2	2	13	5	1	13	7	12	26	68
Muscular weakness
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	3 / 31 (9.68%)	2 / 32 (6.25%)	3 / 60 (5.00%)	4 / 100 (4.00%)	10 / 373 (2.68%)
occurrences all number	1	1	1	0	0	1	1	0	3	2	3	4	10
Musculoskeletal chest pain
subjects affected / exposed	2 / 69 (2.90%)	1 / 42 (2.38%)	3 / 54 (5.56%)	2 / 30 (6.67%)	1 / 15 (6.67%)	6 / 69 (8.70%)	1 / 28 (3.57%)	0 / 3 (0.00%)	1 / 31 (3.23%)	1 / 32 (3.13%)	2 / 60 (3.33%)	7 / 100 (7.00%)	18 / 373 (4.83%)
occurrences all number	2	1	3	2	1	7	1	0	1	1	2	8	19
Musculoskeletal pain
subjects affected / exposed	3 / 69 (4.35%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	1 / 69 (1.45%)	2 / 28 (7.14%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	2 / 60 (3.33%)	1 / 100 (1.00%)	9 / 373 (2.41%)
occurrences all number	4	1	1	0	1	1	2	0	0	0	2	1	10
Pain in extremity
subjects affected / exposed	6 / 69 (8.70%)	2 / 42 (4.76%)	3 / 54 (5.56%)	1 / 30 (3.33%)	1 / 15 (6.67%)	7 / 69 (10.14%)	3 / 28 (10.71%)	0 / 3 (0.00%)	5 / 31 (16.13%)	3 / 32 (9.38%)	6 / 60 (10.00%)	12 / 100 (12.00%)	31 / 373 (8.31%)
occurrences all number	7	3	3	1	1	9	3	0	7	3	6	16	37
Neck pain
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	4 / 69 (5.80%)	1 / 28 (3.57%)	0 / 3 (0.00%)	1 / 31 (3.23%)	1 / 32 (3.13%)	2 / 60 (3.33%)	5 / 100 (5.00%)	8 / 373 (2.14%)
occurrences all number	0	0	1	0	0	4	1	0	1	1	2	5	8
Myalgia
subjects affected / exposed	4 / 69 (5.80%)	3 / 42 (7.14%)	1 / 54 (1.85%)	1 / 30 (3.33%)	2 / 15 (13.33%)	5 / 69 (7.25%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	0 / 32 (0.00%)	1 / 60 (1.67%)	7 / 100 (7.00%)	19 / 373 (5.09%)
occurrences all number	4	3	1	1	2	5	1	0	2	0	1	7	19
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	3 / 54 (5.56%)	0 / 30 (0.00%)	0 / 15 (0.00%)	4 / 69 (5.80%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	0 / 32 (0.00%)	0 / 60 (0.00%)	5 / 100 (5.00%)	10 / 373 (2.68%)
occurrences all number	1	1	4	0	0	4	0	0	1	0	0	5	11
Influenza
subjects affected / exposed	0 / 69 (0.00%)	3 / 42 (7.14%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	1 / 60 (1.67%)	0 / 100 (0.00%)	5 / 373 (1.34%)
occurrences all number	0	3	1	0	0	0	0	0	0	1	1	0	5
Herpes zoster
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	0 / 32 (0.00%)	1 / 60 (1.67%)	2 / 100 (2.00%)	4 / 373 (1.07%)
occurrences all number	1	0	0	0	0	0	1	0	2	0	1	2	4
Erysipelas
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	2 / 60 (3.33%)	0 / 100 (0.00%)	4 / 373 (1.07%)
occurrences all number	0	0	1	0	1	0	0	0	0	4	4	0	6
Epididymitis
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	2 / 32 (6.25%)	2 / 60 (3.33%)	0 / 100 (0.00%)	2 / 373 (0.54%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	2	0	2
Cellulitis
subjects affected / exposed	3 / 69 (4.35%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	4 / 69 (5.80%)	2 / 28 (7.14%)	0 / 3 (0.00%)	3 / 31 (9.68%)	0 / 32 (0.00%)	2 / 60 (3.33%)	7 / 100 (7.00%)	13 / 373 (3.49%)
occurrences all number	3	0	1	0	0	7	3	0	3	0	3	10	17
COVID-19
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	3 / 32 (9.38%)	4 / 60 (6.67%)	3 / 100 (3.00%)	7 / 373 (1.88%)
occurrences all number	0	0	0	0	0	1	1	0	2	3	4	3	7
Nasopharyngitis
subjects affected / exposed	7 / 69 (10.14%)	4 / 42 (9.52%)	1 / 54 (1.85%)	1 / 30 (3.33%)	1 / 15 (6.67%)	3 / 69 (4.35%)	2 / 28 (7.14%)	0 / 3 (0.00%)	3 / 31 (9.68%)	2 / 32 (6.25%)	4 / 60 (6.67%)	6 / 100 (6.00%)	24 / 373 (6.43%)
occurrences all number	7	6	2	1	1	4	3	0	4	3	6	8	31
Staphylococcal infection
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Sepsis
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	1 / 3 (33.33%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	3 / 373 (0.80%)
occurrences all number	0	1	0	0	1	0	0	1	0	0	0	0	3
Rhinitis
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	2 / 373 (0.54%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	0	2
Pyuria
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	1 / 373 (0.27%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1
Pneumonia
subjects affected / exposed	6 / 69 (8.70%)	5 / 42 (11.90%)	1 / 54 (1.85%)	3 / 30 (10.00%)	1 / 15 (6.67%)	5 / 69 (7.25%)	2 / 28 (7.14%)	0 / 3 (0.00%)	2 / 31 (6.45%)	2 / 32 (6.25%)	4 / 60 (6.67%)	7 / 100 (7.00%)	27 / 373 (7.24%)
occurrences all number	8	5	1	3	2	6	2	0	6	2	4	12	35
Oral candidiasis
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	3 / 54 (5.56%)	0 / 30 (0.00%)	0 / 15 (0.00%)	0 / 69 (0.00%)	1 / 28 (3.57%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	2 / 60 (3.33%)	0 / 100 (0.00%)	5 / 373 (1.34%)
occurrences all number	0	0	3	0	0	0	1	0	0	1	2	0	5
Upper respiratory tract infection
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	0 / 54 (0.00%)	1 / 30 (3.33%)	0 / 15 (0.00%)	1 / 69 (1.45%)	1 / 28 (3.57%)	1 / 3 (33.33%)	0 / 31 (0.00%)	1 / 32 (3.13%)	2 / 60 (3.33%)	1 / 100 (1.00%)	5 / 373 (1.34%)
occurrences all number	0	0	0	1	0	1	1	1	0	1	2	1	5
Urinary tract infection
subjects affected / exposed	0 / 69 (0.00%)	1 / 42 (2.38%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	7 / 69 (10.14%)	0 / 28 (0.00%)	0 / 3 (0.00%)	2 / 31 (6.45%)	2 / 32 (6.25%)	2 / 60 (3.33%)	9 / 100 (9.00%)	13 / 373 (3.49%)
occurrences all number	0	1	2	0	0	9	0	0	2	5	5	11	19
Metabolism and nutrition disorders
Hyperkalaemia
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	4 / 54 (7.41%)	1 / 30 (3.33%)	0 / 15 (0.00%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	1 / 32 (3.13%)	1 / 60 (1.67%)	1 / 100 (1.00%)	9 / 373 (2.41%)
occurrences all number	2	1	4	1	0	1	0	0	0	1	1	1	10
Hypoalbuminaemia
subjects affected / exposed	9 / 69 (13.04%)	4 / 42 (9.52%)	5 / 54 (9.26%)	0 / 30 (0.00%)	1 / 15 (6.67%)	5 / 69 (7.25%)	3 / 28 (10.71%)	0 / 3 (0.00%)	6 / 31 (19.35%)	5 / 32 (15.63%)	8 / 60 (13.33%)	11 / 100 (11.00%)	38 / 373 (10.19%)
occurrences all number	12	6	7	0	1	11	3	0	7	8	11	18	55
Hypocalcaemia
subjects affected / exposed	1 / 69 (1.45%)	1 / 42 (2.38%)	0 / 54 (0.00%)	0 / 30 (0.00%)	1 / 15 (6.67%)	5 / 69 (7.25%)	3 / 28 (10.71%)	0 / 3 (0.00%)	4 / 31 (12.90%)	8 / 32 (25.00%)	11 / 60 (18.33%)	9 / 100 (9.00%)	23 / 373 (6.17%)
occurrences all number	1	2	0	0	1	5	5	0	5	9	14	10	28
Hypercalcaemia
subjects affected / exposed	1 / 69 (1.45%)	0 / 42 (0.00%)	3 / 54 (5.56%)	1 / 30 (3.33%)	0 / 15 (0.00%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	1 / 100 (1.00%)	6 / 373 (1.61%)
occurrences all number	1	0	3	1	0	1	0	0	0	0	0	1	6
Decreased appetite
subjects affected / exposed	15 / 69 (21.74%)	6 / 42 (14.29%)	12 / 54 (22.22%)	8 / 30 (26.67%)	4 / 15 (26.67%)	15 / 69 (21.74%)	8 / 28 (28.57%)	0 / 3 (0.00%)	6 / 31 (19.35%)	6 / 32 (18.75%)	14 / 60 (23.33%)	21 / 100 (21.00%)	80 / 373 (21.45%)
occurrences all number	16	6	12	9	4	20	9	0	6	8	17	26	90
Hypokalaemia
subjects affected / exposed	5 / 69 (7.25%)	2 / 42 (4.76%)	2 / 54 (3.70%)	3 / 30 (10.00%)	1 / 15 (6.67%)	3 / 69 (4.35%)	1 / 28 (3.57%)	0 / 3 (0.00%)	2 / 31 (6.45%)	4 / 32 (12.50%)	5 / 60 (8.33%)	5 / 100 (5.00%)	23 / 373 (6.17%)
occurrences all number	6	5	2	3	1	3	1	0	3	11	12	6	35
Hypomagnesaemia
subjects affected / exposed	2 / 69 (2.90%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	1 / 69 (1.45%)	0 / 28 (0.00%)	0 / 3 (0.00%)	1 / 31 (3.23%)	2 / 32 (6.25%)	2 / 60 (3.33%)	2 / 100 (2.00%)	7 / 373 (1.88%)
occurrences all number	2	0	1	0	0	1	0	0	1	3	3	2	8
Hypophosphataemia
subjects affected / exposed	9 / 69 (13.04%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	0 / 15 (0.00%)	3 / 69 (4.35%)	3 / 28 (10.71%)	0 / 3 (0.00%)	4 / 31 (12.90%)	0 / 32 (0.00%)	3 / 60 (5.00%)	7 / 100 (7.00%)	20 / 373 (5.36%)
occurrences all number	12	0	1	0	0	3	4	0	10	0	4	13	30
Hypophagia
subjects affected / exposed	0 / 69 (0.00%)	0 / 42 (0.00%)	1 / 54 (1.85%)	0 / 30 (0.00%)	1 / 15 (6.67%)	0 / 69 (0.00%)	0 / 28 (0.00%)	0 / 3 (0.00%)	0 / 31 (0.00%)	0 / 32 (0.00%)	0 / 60 (0.00%)	0 / 100 (0.00%)	2 / 373 (0.54%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0	0	2
Hyponatraemia
subjects affected / exposed	1 / 69 (1.45%)	2 / 42 (4.76%)	3 / 54 (5.56%)	0 / 30 (0.00%)	2 / 15 (13.33%)	3 / 69 (4.35%)	1 / 28 (3.57%)	1 / 3 (33.33%)	0 / 31 (0.00%)	2 / 32 (6.25%)	3 / 60 (5.00%)	3 / 100 (3.00%)	15 / 373 (4.02%)
occurrences all number	1	2	3	0	2	4	1	2	0	6	7	4	21

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

27 Feb 2015

Assessment of ALK rearrangement determined with a validated test is considered as part of the non-squamous NSCLC subject’s standard of care and therefore ALK-negative rearrangement status was required for subjects with non-squamous NSCLC in order to be enrolled in the study. The inclusion and exclusion criterion was amended accordingly.

11 Sep 2015

A new cohort (Cohort 4) was implemented to enroll subjects with MET mutations, irrespective of MET amplification status. For subjects already enrolled in the study prior to the implementation of this amendment, the MET mutation status was to be determined retrospectively, however these subjects remained in the cohort to which they were initially enrolled. Photosensitization: precautionary measures against ultraviolet exposure were included. Dose modification guidelines for hepatotoxicity were modified in regard to discontinuing study medication(s) with concurrent elevation of ALT and/or AST > 3 × ULN and total bilirubin > 2 × ULN with ALP < 2 × ULN, in the absence of signs of cholestasis, hemolysis, and alternative causes of the liver injury. Specific work-up guidelines for potential drug-induced liver injury (DILI) cases were added to the protocol. The dose modification rules as well as the follow-up evaluations for hepatic toxicities were also updated accordingly. Clinical PK data were updated with the recent data from study CINC280X2102 and CIN280X1101 that identified CMN288 as a major metabolite of capmatinib. Characterization of CMN288 metabolite was added in the PK objective.

28 Jul 2016

To further investigate and better characterize the optimal GCN as predictor of response to capmatinib. The following 2 subcohorts were implemented within Cohort 1 (Cohort 1: Subjects with a MET GCN of ≥ 6): • Subcohort 1a (referred to as Cohort 1a in the CSR): Subjects with a MET GCN of ≥ 10, or • Subcohort 1b (referred to as Cohort 1b in the CSR): Subjects with a MET GCN of ≥ 6 and < 10 Each of the two subcohorts were to be tested independently. Restrictions on the use of PPIs as concomitant medications were removed.

17 Nov 2016

A new cohort (Cohort 5) was added to enroll treatment-naïve subjects with MET dysregulation: Cohort 5: Treatment-naïve subjects with MET dysregulation: •Subcohort 5a (referred to as Cohort 5a in the CSR): Subjects with a MET GCN ≥ 10 (without MET mutations) •Subcohort 5b (referred to as Cohort 5b in the CSR): Subjects with MET mutations regardless of MET GCN

13 Feb 2018

A new expansion Cohort 6 was added for enrollment of additional 30 subjects approximately with advanced NSCLC pretreated with one prior line of systemic therapy harboring either MET amplification (GCN ≥ 10) or MET mutations (irrespective of MET GCN). Exclusion criteria, the list of prohibited medications, the list of medications to be used with caution and the criteria for dose modifications were updated based on the latest capmatinib clinical data per IB, edition 9.

28 Feb 2019

A new expansion Cohort 7 was added for the enrollment of approximately 27 treatment-naïve subjects with advanced NSCLC harboring MET exon 14 skipping mutations (regardless of MET GCN). Close the recruitment of NSCLC subjects with GCN ≥ 10 in Cohort 5a and Cohort 6. Therefore, as of 25-Jan-2019, pre-screening for MET GCN ≥ 10 NSCLC subjects and central FISH (Fluorescence In Situ Hybridization) testing for MET GCN eligibility was discontinued. Cycle 1 Day 1 blood collection increased to 3x10 mL from 2x10 mL. Implement an additional on-treatment blood sample collection (2 x 10 mL) at C3D1

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

Due to EudraCT system limitations, which EMA is aware of, data using 9999 as data points in this record are not an accurate representation of the clinical trial results.

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

Clinical Trial Results: A phase II, multicenter study of oral cMET inhibitor INC280 in adult patients with EGFR wild-type (wt), advanced non-small cell lung cancer (NSCLC)

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) assessment

Primary: Overall Response Rate (ORR) by Blinded Independent Review Committee (BIRC) assessment

Secondary: Duration of Response (DOR) by BIRC assessment

Secondary: Duration of Response (DOR) by BIRC assessment

Secondary: ORR by investigator assessment

Secondary: ORR by investigator assessment

Secondary: DOR by investigator assessment

Secondary: DOR by investigator assessment

Secondary: Time to Response (TTR) by BIRC assessment

Secondary: Time to Response (TTR) by BIRC assessment

Secondary: TTR by investigator assessment

Secondary: TTR by investigator assessment

Secondary: Disease Control Rate (DCR)

Secondary: Disease Control Rate (DCR)

Secondary: Progression-Free Survival

Secondary: Progression-Free Survival

Secondary: Overall Survival (OS)

Secondary: Overall Survival (OS)

Secondary: Pharmacokinetic (PK) concentrations of capmatinib

Secondary: Pharmacokinetic (PK) concentrations of capmatinib

Secondary: Area under the plasma concentration-time curve from zero to time infinity (AUCinf) of CMN288

Secondary: Area under the plasma concentration-time curve from zero to time infinity (AUCinf) of CMN288

Secondary: Area under the plasma concentration-time curve from zero to time infinity (AUCinf) of capmatinib

Secondary: Area under the plasma concentration-time curve from zero to time infinity (AUCinf) of capmatinib

Secondary: Maximum concentration (Cmax) of capmatinib

Secondary: Maximum concentration (Cmax) of capmatinib

Secondary: Maximum concentration (Cmax) of CMN288

Secondary: Maximum concentration (Cmax) of CMN288

Secondary: Time to reach maximum concentration (Tmax) of CMN288

Secondary: Time to reach maximum concentration (Tmax) of CMN288

Secondary: Time to reach maximum concentration (Tmax) of capmatinib

Secondary: Time to reach maximum concentration (Tmax) of capmatinib

Secondary: Elimination half-life (T1/2) of capmatinib

Secondary: Elimination half-life (T1/2) of capmatinib

Secondary: Elimination half-life (T1/2) of CMN288

Secondary: Elimination half-life (T1/2) of CMN288

Post-hoc: All collected deaths

Post-hoc: All collected deaths

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A phase II, multicenter study of oral cMET inhibitor INC280 in adult patients with EGFR wild-type (wt), advanced non-small cell lung cancer (NSCLC)