Download PDF

Clinical Trial Results:
A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of INCB054828 in Subjects With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Including FGFR2 Translocations Who Failed Previous Therapy

Summary
EudraCT number	2016-002422-36
Trial protocol	DE BE FR GB IT
Global end of trial date	01 Feb 2022

Results information
Results version number	v1(current)
This version publication date	11 Feb 2023
First version publication date	11 Feb 2023
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

INCB 54828-202

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

Incyte Corporation

Sponsor organisation address

1801 Augustine Cutoff Drive, Wilmington, United States, 19803

Public contact

Study Director, Incyte Corporation, 1 18554633463, medinfo@incyte.com

Scientific contact

Study Director, Incyte Corporation, 1 18554633463, medinfo@incyte.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

01 Feb 2022

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

01 Feb 2022

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study was evaluate the efficacy of pemigatinib in participants with advanced/metastatic or surgically unresectable cholangiocarcinoma with fibroblast growth factor (FGF) receptor 2 (FGFR2) translocation who have failed at least 1 previous treatment.

Protection of trial subjects

This study was to be performed in accordance with ethical principles that have their origin in the Declaration of Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the United States Code of Federal Regulations Parts 11, 50, 54, 56, and 312, as well as International Conference on Harmonisation Good Clinical Practice (ICH GCP) consolidated guidelines (E6) and applicable regulatory requirements.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Jan 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 2

Country: Number of subjects enrolled

France: 10

Country: Number of subjects enrolled

Germany: 5

Country: Number of subjects enrolled

Israel: 3

Country: Number of subjects enrolled

Italy: 8

Country: Number of subjects enrolled

Japan: 3

Country: Number of subjects enrolled

Korea, Republic of: 12

Country: Number of subjects enrolled

Spain: 4

Country: Number of subjects enrolled

Taiwan: 1

Country: Number of subjects enrolled

Thailand: 4

Country: Number of subjects enrolled

United Kingdom: 6

Country: Number of subjects enrolled

United States: 89

Worldwide total number of subjects

147

EEA total number of subjects

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)

101

From 65 to 84 years

85 years and over

Subject disposition

Top of page

Recruitment details

Screening details

This study enrolled participants at 68 study sites in the United States, South Korea, United Kingdom, France, Italy, Thailand, Germany, Belgium, Israel, Spain, Japan, and Taiwan.

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 A: FGFR2 rearrangements or fusions

Arm description

Participants with fibroblast growth factor (FGF) receptor 2 (FGFR2) rearrangements or fusions self-administered oral pemigatinib at a starting dose of 13.5 milligrams (mg) once daily (QD) on a 2-weeks-on therapy/1-week-off schedule in 21-day cycles. Pemigatinib was administered until documented disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

pemigatinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2.0- and 4.5-mg tablets; starting dose of 13.5 mg

Cohort B: Other FGF/FGFR alterations

Arm description

Participants with all other FGF/FGFR alterations self-administered oral pemigatinib at a starting dose of 13.5 mg QD on a 2-weeks-on therapy/1-week-off schedule in 21-day cycles. Pemigatinib was administered until documented disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

pemigatinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2.0- and 4.5-mg tablets; starting dose of 13.5 mg

Cohort C: negative for FGF/FGFR alterations

Arm description

Participants with no FGF/FGFR alterations self-administered oral pemigatinib at a starting dose of 13.5 mg QD on a 2-weeks-on therapy/1-week-off schedule in 21-day cycles (United States only). Pemigatinib was administered until documented disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

pemigatinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2.0- and 4.5-mg tablets; starting dose of 13.5 mg

Other

Arm description

Participants with an FGF/FGFR status for whom the local laboratory FGF/FGFR results could not be confirmed centrally self-administered oral pemigatinib at a starting dose of 13.5 mg QD on a 2-weeks-on therapy/1-week-off schedule in 21-day cycles. Pemigatinib was administered until documented disease progression or unacceptable toxicity.

Arm type

Experimental

Investigational medicinal product name

pemigatinib

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

2.0- and 4.5-mg tablets; starting dose of 13.5 mg

Number of subjects in period 1	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Started	108	20	17	2
Completed	0	0	0	0
Not completed	108	20	17	2
Adverse event, serious fatal	73	18	15	2
Physician decision	1	-	-	-
Consent withdrawn by subject	7	2	1	-
Rolled Over to Another Study	1	-	-	-
Progressive Disease	4	-	1	-
Study Terminated by Sponsor	19	-	-	-
Lost to follow-up	3	-	-	-

Baseline characteristics

Top of page

Reporting group title

Cohort A: FGFR2 rearrangements or fusions

Reporting group description

Reporting group title

Cohort B: Other FGF/FGFR alterations

Reporting group description

Reporting group title

Cohort C: negative for FGF/FGFR alterations

Reporting group description

Reporting group title

Other

Reporting group description

Reporting group values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other	Total
Number of subjects	108	20	17	2	147
Age categorical
Units: Subjects
Adults (18-64 years)	83	10	6	2	101
From 65-84 years	25	10	11	0	46
85 years and over	0	0	0	0	0
Age Continuous
Units: years
arithmetic mean (standard deviation)	55.2 ( 12.00 )	61.9 ( 10.99 )	65.6 ( 7.12 )	41.0 ( 14.14 )	-
Sex: Female, Male
Units: participants
Female	66	11	7	1	85
Male	42	9	10	1	62
Race, Customized
Units: Subjects
White	79	9	14	2	104
Black or African American	7	0	1	0	8
Asian	12	11	0	0	23
American-Indian/Alaska Native	0	0	1	0	1
Captured as "Other"	4	0	1	0	5
Missing	6	0	0	0	6
Ethnicity, Customized
Units: Subjects
Hispanic or Latino	2	0	4	0	6
Not Hispanic or Latino	88	18	13	2	121
Not Reported	15	0	0	0	15
Unknown	1	0	0	0	1
Captured as "Other"	2	2	0	0	4

End points

Top of page

Reporting group title

Cohort A: FGFR2 rearrangements or fusions

Reporting group description

Reporting group title

Cohort B: Other FGF/FGFR alterations

Reporting group description

Reporting group title

Cohort C: negative for FGF/FGFR alterations

Reporting group description

Reporting group title

Other

Reporting group description

Subject analysis set title

Cohort A + Cohort B

Subject analysis set type

Full analysis

Subject analysis set description

Participants with FGFR2 rearrangements or fusions (Cohort A) or with all other FGF/FGFR alterations (Cohort B) self-administered oral pemigatinib at a starting dose of 13.5 mg QD on a 2-weeks-on therapy/1-week-off schedule in 21-day cycles. Pemigatinib was administered until documented disease progression or unacceptable toxicity.

Subject analysis set title

All cohorts

Subject analysis set type

Full analysis

Subject analysis set description

Participants in the Pharmacokinetic Population with FGFR2 rearrangements or fusions (Cohort A), participants with all other FGF/FGFR alterations (Cohort B), participants with no FGF/FGFR alterations (Cohort C; United States only), and participants with an FGF/FGFR status for whom the local laboratory FGF/FGFR results could not be confirmed centrally (Other) self-administered oral pemigatinib at a starting dose of 13.5 mg QD on a 2-weeks-on therapy/1-week-off schedule in 21-day cycles. Pemigatinib was administered until documented disease progression or unacceptable toxicity.

Primary: Objective response rate (ORR) in participants with FGFR2 rearrangements or fusions

Top of page

End point title

Objective response rate (ORR) in participants with FGFR2 rearrangements or fusions ^[1]

End point description

ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) at any post-Baseline visit prior to first progressive disease (PD), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. ORR was based on central genomics laboratory results. Response was based on review of scans by an independent centralized radiological review committee.

End point type

Primary

End point timeframe

up to 1527 days

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: Statistical analysis was not conducted for this endpoint.

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Number of subjects analysed	108	0 ^[2]	0 ^[3]	0 ^[4]
Units: percentage of participants
number (confidence interval 95%)	37.0 (27.94 to 46.86)	( to )	( to )	( to )

Notes
[2] - Analysis was conducted in participants with FGFR2 rearrangements or fusions.
[3] - Analysis was conducted in participants with FGFR2 rearrangements or fusions.
[4] - Analysis was conducted in participants with FGFR2 rearrangements or fusions.

No statistical analyses for this end point

Secondary: ORR in participants FGF/FGFR alterations other than FGFR2 rearrangements or fusions

Top of page

End point title

ORR in participants FGF/FGFR alterations other than FGFR2 rearrangements or fusions

End point description

ORR was defined as the percentage of participants with a best overall response of CR or PR at any post-Baseline visit prior to first PD, per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. ORR was based on central genomics laboratory results. Response was based on review of scans by an independent centralized radiological review committee.

End point type

Secondary

End point timeframe

up to 424 days

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Number of subjects analysed	0 ^[5]	20	0 ^[6]	0 ^[7]
Units: percentage of participants
number (confidence interval 95%)	( to )	0.0 (0.0 to 16.84)	( to )	( to )

Notes
[5] - Analysis was conducted in participants with other FGF/FGFR alterations.
[6] - Analysis was conducted in participants with other FGF/FGFR alterations.
[7] - Analysis was conducted in participants with other FGF/FGFR alterations.

No statistical analyses for this end point

Secondary: ORR in all participants with FGF/FGFR alterations

Top of page

End point title

ORR in all participants with FGF/FGFR alterations

End point description

End point type

Secondary

End point timeframe

up to 1527 days

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other	Cohort A + Cohort B
Number of subjects analysed	0 ^[8]	0 ^[9]	0 ^[10]	0 ^[11]	128
Units: percentage of participants
number (confidence interval 95%)	( to )	( to )	( to )	( to )	31.3 (23.35 to 40.04)

Notes
[8] - Analysis was conducted in all participants with FGF/FGFR alterations.
[9] - Analysis was conducted in all participants with FGF/FGFR alterations.
[10] - Analysis was conducted in all participants with FGF/FGFR alterations.
[11] - Analysis was conducted in all participants with FGF/FGFR alterations.

No statistical analyses for this end point

Secondary: ORR in participants negative for FGF/FGFR alterations

Top of page

End point title

ORR in participants negative for FGF/FGFR alterations

End point description

End point type

Secondary

End point timeframe

up to 143 days

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Number of subjects analysed	0 ^[12]	0 ^[13]	17	0 ^[14]
Units: percentage of participants
number (confidence interval 95%)	( to )	( to )	0.0 (0.0 to 19.51)	( to )

Notes
[12] - Analysis was conducted in participants negative for FGF/FGFR alterations.
[13] - Analysis was conducted in participants negative for FGF/FGFR alterations.
[14] - Analysis was conducted in participants negative for FGF/FGFR alterations.

No statistical analyses for this end point

Secondary: Progression-free survival (PFS)

Top of page

End point title

Progression-free survival (PFS)

End point description

PFS was defined as the length of time from the first dose of study drug (Day 1) to the earlier of death or disease progression by RECIST v1.1, as assessed by the independent centralized radiological review committee.

End point type

Secondary

End point timeframe

up to 50.17 months

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Number of subjects analysed	108	20	17	0 ^[15]
Units: months
median (confidence interval 95%)	7.03 (6.08 to 10.48)	2.10 (1.18 to 4.86)	1.51 (1.38 to 1.84)	( to )

Notes
[15] - Analysis was not conducted in this treatment group.

No statistical analyses for this end point

Secondary: Duration of response (DOR)

Top of page

End point title

Duration of response (DOR)

End point description

DOR was defined as the time from the first overall response contributing to an objective response (CR or PR) as assessed by an independent centralized radiological review committee to the earlier of death or first overall response of PD occurring after the first overall response contributing to the objective response. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion.

End point type

Secondary

End point timeframe

up to 47.11 months

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Number of subjects analysed	40	0 ^[16]	0 ^[17]	0 ^[18]
Units: months
median (confidence interval 95%)	9.13 (6.01 to 14.49)	( to )	( to )	( to )

Notes
[16] - Analysis was conducted in those participants with a CR or PR.
[17] - Analysis was conducted in those participants with a CR or PR.
[18] - Analysis was not conducted in this treatment group.

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

DCR was defined as the proportion of participants with an overall response of CR, PR, or stable disease (SD), per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to <10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD.

End point type

Secondary

End point timeframe

up to 1527 days

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Number of subjects analysed	108	20	17	0 ^[19]
Units: percentage of participants
number (confidence interval 95%)	82.4 (73.9 to 89.1)	40.0 (19.1 to 63.9)	17.6 (3.8 to 43.4)	( to )

Notes
[19] - Analysis was not conducted in this treatment group.

No statistical analyses for this end point

Secondary: Overall survival

Top of page

End point title

Overall survival

End point description

Overall survival was defined as the length of time from the first dose of study drug (Day 1) until the date of death due to any cause.

End point type

Secondary

End point timeframe

up to 51.32 months

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Number of subjects analysed	108	20	17	0 ^[20]
Units: months
median (confidence interval 95%)	17.48 (14.36 to 22.93)	6.70 (2.10 to 10.55)	3.98 (1.97 to 4.60)	( to )

Notes
[20] - Analysis was not conducted in this treatment group.

No statistical analyses for this end point

Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

Top of page

End point title

Number of participants with any treatment-emergent adverse event (TEAE)

End point description

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study drug(s). A TEAE was defined as any adverse event either reported for the first time or the worsening of a pre-existing event after the first dose of study drug and within 30 days of the last dose of study drug.

End point type

Secondary

End point timeframe

up to 1584 days

End point values	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other
Number of subjects analysed	108	20	17	2
Units: participants	108	20	17	2

No statistical analyses for this end point

Secondary: First-order absorption rate constant (ka) of pemigatinib

Top of page

End point title

First-order absorption rate constant (ka) of pemigatinib

End point description

First-order absorption rate constant is defined as the rate at which a drug enters into the system.

End point type

Secondary

End point timeframe

Predose; 1-2 hours post-dose; 4-12 hours post-dose

End point values	All cohorts
Number of subjects analysed	136
Units: 1/hour
arithmetic mean (standard deviation)	1.29 ( 0.827 )

No statistical analyses for this end point

Secondary: CL/F of pemigatinib

Top of page

End point title

CL/F of pemigatinib

End point description

CL/F is defined as apparent oral clearance.

End point type

Secondary

End point timeframe

Predose; 1-2 hours post-dose; 4-12 hours post-dose

End point values	All cohorts
Number of subjects analysed	136
Units: Liters/hour
arithmetic mean (standard deviation)	12.2 ( 5.28 )

No statistical analyses for this end point

Secondary: Vc/F of pemigatinib

Top of page

End point title

Vc/F of pemigatinib

End point description

Vc/F is defined as the apparent volume of distribution for the central compartment of pemigatinib.

End point type

Secondary

End point timeframe

Predose; 1-2 hours post-dose; 4-12 hours post-dose

End point values	All cohorts
Number of subjects analysed	136
Units: Liters
arithmetic mean (standard deviation)	144 ( 55.7 )

No statistical analyses for this end point

Secondary: Vp/F of pemigatinib

Top of page

End point title

Vp/F of pemigatinib

End point description

Vp/F is defined as the apparent volume of distribution for the tissue (peripheral) compartment.

End point type

Secondary

End point timeframe

Predose; 1-2 hours post-dose; 4-12 hours post-dose

End point values	All cohorts
Number of subjects analysed	136
Units: Liters
arithmetic mean (standard deviation)	85.6 ( 30.5 )

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

up to 1584 days

Adverse event reporting additional description

Treatment-emergent adverse events, defined as adverse events either reported for the first time or the worsening of pre-existing events after the first dose of study drug and within 30 days of the last dose of study drug, have been reported.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

Reporting group title

Cohort A: FGFR2 rearrangements or fusions

Reporting group description

Reporting group title

Cohort B: Other FGF/FGFR alterations

Reporting group description

Reporting group title

Cohort C: negative for FGF/FGFR alterations

Reporting group description

Reporting group title

Other

Reporting group description

Reporting group title

Total

Reporting group description

Total

Serious adverse events	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other	Total
Total subjects affected by serious adverse events
subjects affected / exposed	46 / 108 (42.59%)	10 / 20 (50.00%)	12 / 17 (70.59%)	0 / 2 (0.00%)	68 / 147 (46.26%)
number of deaths (all causes)	76	18	15	2	111
number of deaths resulting from adverse events	3	2	1	0	6
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Prostate cancer
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Thrombosis
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chills
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Complication associated with device
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Fatigue
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Non-cardiac chest pain
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	5 / 108 (4.63%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences causally related to treatment / all	0 / 7	0 / 1	0 / 1	0 / 0	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic reaction
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	2 / 108 (1.85%)	2 / 20 (10.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	5 / 147 (3.40%)
occurrences causally related to treatment / all	0 / 2	0 / 2	0 / 1	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
Pneumonia aspiration
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Device leakage
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device occlusion
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Blood bilirubin increased
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood creatinine increased
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Cerebrovascular accident
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Embolic cerebral infarction
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Paraplegia
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 1	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Optic ischaemic neuropathy
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Retinal artery occlusion
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Retinal detachment
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	4 / 108 (3.70%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences causally related to treatment / all	2 / 6	0 / 1	0 / 2	0 / 0	2 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Colitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dysphagia
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal haemorrhage
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Haematemesis
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Melaena
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstruction gastric
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophageal varices haemorrhage
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Rectal haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Small intestinal obstruction
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	0 / 5	0 / 0	0 / 2	0 / 0	0 / 7
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Varices oesophageal
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Biliary obstruction
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
Biloma
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis
subjects affected / exposed	5 / 108 (4.63%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences causally related to treatment / all	0 / 8	0 / 0	0 / 1	0 / 0	0 / 9
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
Jaundice
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant biliary obstruction
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	1 / 2	0 / 0	0 / 1	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Endocrine disorders
Hypercalcaemia of malignancy
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypothyroidism
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Inappropriate antidiuretic hormone secretion
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Flank pain
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bacteraemia
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Biliary tract infection
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Catheter site infection
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholangitis infective
subjects affected / exposed	3 / 108 (2.78%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Clostridium difficile infection
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Enterobacter bacteraemia
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Kidney infection
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	0 / 4	0 / 0	0 / 1	0 / 0	0 / 5
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia pneumococcal
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pseudomonal bacteraemia
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
Septic shock
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin infection
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Typhoid fever
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dehydration
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Failure to thrive
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2
Hypercalcaemia
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	0 / 2	0 / 1	0 / 0	0 / 0	0 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperkalaemia
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyperuricaemia
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hyponatraemia
subjects affected / exposed	1 / 108 (0.93%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences causally related to treatment / all	0 / 1	1 / 2	0 / 0	0 / 0	1 / 3
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	Cohort A: FGFR2 rearrangements or fusions	Cohort B: Other FGF/FGFR alterations	Cohort C: negative for FGF/FGFR alterations	Other	Total
Total subjects affected by non serious adverse events
subjects affected / exposed	108 / 108 (100.00%)	20 / 20 (100.00%)	17 / 17 (100.00%)	2 / 2 (100.00%)	147 / 147 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Malignant ascites
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Malignant pleural effusion
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Tumour associated fever
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Hypertension
subjects affected / exposed	9 / 108 (8.33%)	3 / 20 (15.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	12 / 147 (8.16%)
occurrences all number	11	4	0	0	15
Hypotension
subjects affected / exposed	5 / 108 (4.63%)	2 / 20 (10.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	9 / 147 (6.12%)
occurrences all number	9	2	3	0	14
General disorders and administration site conditions
Asthenia
subjects affected / exposed	15 / 108 (13.89%)	4 / 20 (20.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	20 / 147 (13.61%)
occurrences all number	34	9	1	0	44
Chills
subjects affected / exposed	6 / 108 (5.56%)	0 / 20 (0.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	8 / 147 (5.44%)
occurrences all number	8	0	2	0	10
Fatigue
subjects affected / exposed	50 / 108 (46.30%)	5 / 20 (25.00%)	9 / 17 (52.94%)	0 / 2 (0.00%)	64 / 147 (43.54%)
occurrences all number	60	6	9	0	75
Gait disturbance
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Influenza like illness
subjects affected / exposed	6 / 108 (5.56%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	7	0	0	0	7
Malaise
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Non-cardiac chest pain
subjects affected / exposed	3 / 108 (2.78%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	5 / 147 (3.40%)
occurrences all number	3	2	1	0	6
Oedema peripheral
subjects affected / exposed	16 / 108 (14.81%)	4 / 20 (20.00%)	6 / 17 (35.29%)	0 / 2 (0.00%)	26 / 147 (17.69%)
occurrences all number	21	4	6	0	31
Pain
subjects affected / exposed	4 / 108 (3.70%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	5 / 147 (3.40%)
occurrences all number	4	0	1	0	5
Performance status decreased
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Pyrexia
subjects affected / exposed	11 / 108 (10.19%)	3 / 20 (15.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	16 / 147 (10.88%)
occurrences all number	20	3	2	0	25
Thirst
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Reproductive system and breast disorders
Breast pain
subjects affected / exposed	3 / 108 (2.78%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	3	1	0	0	4
Gynaecomastia
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Penile pain
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Respiratory, thoracic and mediastinal disorders
Atelectasis
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Cough
subjects affected / exposed	10 / 108 (9.26%)	0 / 20 (0.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	12 / 147 (8.16%)
occurrences all number	12	0	2	0	14
Dysphonia
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	2	0	1	0	3
Dyspnoea
subjects affected / exposed	10 / 108 (9.26%)	3 / 20 (15.00%)	3 / 17 (17.65%)	0 / 2 (0.00%)	16 / 147 (10.88%)
occurrences all number	12	3	3	0	18
Dyspnoea exertional
subjects affected / exposed	3 / 108 (2.78%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	3	0	1	0	4
Epistaxis
subjects affected / exposed	19 / 108 (17.59%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	20 / 147 (13.61%)
occurrences all number	24	1	0	0	25
Laryngeal inflammation
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Nasal congestion
subjects affected / exposed	8 / 108 (7.41%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	11 / 147 (7.48%)
occurrences all number	9	1	2	0	12
Nasal dryness
subjects affected / exposed	13 / 108 (12.04%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	13 / 147 (8.84%)
occurrences all number	14	0	0	0	14
Oropharyngeal pain
subjects affected / exposed	11 / 108 (10.19%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	13 / 147 (8.84%)
occurrences all number	13	2	0	0	15
Pulmonary embolism
subjects affected / exposed	0 / 108 (0.00%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	0	2	0	0	2
Rhinitis allergic
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Sinus pain
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Stridor
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Psychiatric disorders
Confusional state
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	2	0	1	0	3
Depression
subjects affected / exposed	6 / 108 (5.56%)	2 / 20 (10.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	9 / 147 (6.12%)
occurrences all number	6	2	1	0	9
Hallucination
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Insomnia
subjects affected / exposed	13 / 108 (12.04%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	15 / 147 (10.20%)
occurrences all number	13	2	0	0	15
Nervousness
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	3 / 108 (2.78%)	0 / 20 (0.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	4 / 147 (2.72%)
occurrences all number	3	0	0	1	4
Alanine aminotransferase increased
subjects affected / exposed	12 / 108 (11.11%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	13 / 147 (8.84%)
occurrences all number	16	0	1	0	17
Aspartate aminotransferase increased
subjects affected / exposed	9 / 108 (8.33%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	12 / 147 (8.16%)
occurrences all number	16	3	2	0	21
Bilirubin conjugated increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Blood 1,25-dihydroxycholecalciferol decreased
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	4	1	0	0	5
Blood 1,25-dihydroxycholecalciferol increased
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	3	1	0	0	4
Blood 25-hydroxycholecalciferol decreased
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Blood alkaline phosphatase increased
subjects affected / exposed	12 / 108 (11.11%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	15 / 147 (10.20%)
occurrences all number	16	1	2	0	19
Blood bilirubin increased
subjects affected / exposed	6 / 108 (5.56%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	9	0	1	0	10
Blood chloride decreased
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	4	0	0	5
Blood creatinine increased
subjects affected / exposed	9 / 108 (8.33%)	2 / 20 (10.00%)	4 / 17 (23.53%)	0 / 2 (0.00%)	15 / 147 (10.20%)
occurrences all number	12	2	4	0	18
Blood parathyroid hormone decreased
subjects affected / exposed	3 / 108 (2.78%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	4	2	0	0	6
Blood urea increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
C-reactive protein increased
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Electrocardiogram QT prolonged
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	2	1	0	0	3
Lipase increased
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Lymphocyte count decreased
subjects affected / exposed	4 / 108 (3.70%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	5	2	1	0	8
Platelet count decreased
subjects affected / exposed	8 / 108 (7.41%)	1 / 20 (5.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	10 / 147 (6.80%)
occurrences all number	15	1	0	1	17
Transaminases increased
subjects affected / exposed	1 / 108 (0.93%)	3 / 20 (15.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	1	5	0	0	6
Tri-iodothyronine free increased
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Weight decreased
subjects affected / exposed	20 / 108 (18.52%)	4 / 20 (20.00%)	1 / 17 (5.88%)	1 / 2 (50.00%)	26 / 147 (17.69%)
occurrences all number	23	4	1	1	29
Weight increased
subjects affected / exposed	4 / 108 (3.70%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	5 / 147 (3.40%)
occurrences all number	7	2	0	0	9
Injury, poisoning and procedural complications
Accidental overdose
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Fall
subjects affected / exposed	8 / 108 (7.41%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	9 / 147 (6.12%)
occurrences all number	13	0	1	0	14
Cardiac disorders
Palpitations
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	3 / 147 (2.04%)
occurrences all number	2	0	0	1	3
Sinus tachycardia
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Tachycardia
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	4	0	1	0	5
Nervous system disorders
Coma
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Dizziness
subjects affected / exposed	19 / 108 (17.59%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	21 / 147 (14.29%)
occurrences all number	23	1	1	0	25
Dysgeusia
subjects affected / exposed	45 / 108 (41.67%)	3 / 20 (15.00%)	3 / 17 (17.65%)	2 / 2 (100.00%)	53 / 147 (36.05%)
occurrences all number	49	5	3	2	59
Generalised tonic-clonic seizure
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Headache
subjects affected / exposed	20 / 108 (18.52%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	23 / 147 (15.65%)
occurrences all number	32	1	2	0	35
Neuropathy peripheral
subjects affected / exposed	7 / 108 (6.48%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	9 / 147 (6.12%)
occurrences all number	8	2	0	0	10
Seizure
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Somnolence
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	1	1	1	0	3
Taste disorder
subjects affected / exposed	7 / 108 (6.48%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	9	0	0	0	9
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	16 / 108 (14.81%)	2 / 20 (10.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	20 / 147 (13.61%)
occurrences all number	27	2	2	0	31
Febrile neutropenia
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Iron deficiency anaemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Lymphopenia
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	3 / 108 (2.78%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	3	1	0	0	4
Eye disorders
Cataract
subjects affected / exposed	7 / 108 (6.48%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	10	0	0	0	10
Chorioretinal scar
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Dry eye
subjects affected / exposed	38 / 108 (35.19%)	1 / 20 (5.00%)	1 / 17 (5.88%)	1 / 2 (50.00%)	41 / 147 (27.89%)
occurrences all number	45	1	1	1	48
Episcleritis
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Eye discharge
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Eye pain
subjects affected / exposed	6 / 108 (5.56%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	6	0	0	0	6
Growth of eyelashes
subjects affected / exposed	8 / 108 (7.41%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	8 / 147 (5.44%)
occurrences all number	8	0	0	0	8
Keratitis
subjects affected / exposed	4 / 108 (3.70%)	0 / 20 (0.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	5 / 147 (3.40%)
occurrences all number	4	0	0	1	5
Lacrimation increased
subjects affected / exposed	7 / 108 (6.48%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	12	0	0	0	12
Ocular hyperaemia
subjects affected / exposed	6 / 108 (5.56%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	6	0	0	0	6
Presbyopia
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Punctate keratitis
subjects affected / exposed	8 / 108 (7.41%)	1 / 20 (5.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	10 / 147 (6.80%)
occurrences all number	8	1	0	1	10
Subretinal fluid
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Trichiasis
subjects affected / exposed	11 / 108 (10.19%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	13 / 147 (8.84%)
occurrences all number	11	2	0	0	13
Trichomegaly
subjects affected / exposed	2 / 108 (1.85%)	0 / 20 (0.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	3 / 147 (2.04%)
occurrences all number	2	0	0	1	3
Vitreous floaters
subjects affected / exposed	5 / 108 (4.63%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	6	1	0	0	7
Gastrointestinal disorders
Abdominal distension
subjects affected / exposed	9 / 108 (8.33%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	10 / 147 (6.80%)
occurrences all number	10	0	1	0	11
Abdominal pain
subjects affected / exposed	22 / 108 (20.37%)	3 / 20 (15.00%)	3 / 17 (17.65%)	1 / 2 (50.00%)	29 / 147 (19.73%)
occurrences all number	39	3	3	1	46
Abdominal pain upper
subjects affected / exposed	11 / 108 (10.19%)	2 / 20 (10.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	14 / 147 (9.52%)
occurrences all number	16	2	1	0	19
Ascites
subjects affected / exposed	4 / 108 (3.70%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	5 / 147 (3.40%)
occurrences all number	4	1	0	0	5
Constipation
subjects affected / exposed	46 / 108 (42.59%)	5 / 20 (25.00%)	2 / 17 (11.76%)	1 / 2 (50.00%)	54 / 147 (36.73%)
occurrences all number	68	6	2	1	77
Diarrhoea
subjects affected / exposed	58 / 108 (53.70%)	5 / 20 (25.00%)	6 / 17 (35.29%)	1 / 2 (50.00%)	70 / 147 (47.62%)
occurrences all number	169	15	6	1	191
Dry mouth
subjects affected / exposed	42 / 108 (38.89%)	5 / 20 (25.00%)	1 / 17 (5.88%)	2 / 2 (100.00%)	50 / 147 (34.01%)
occurrences all number	49	5	1	2	57
Dyspepsia
subjects affected / exposed	14 / 108 (12.96%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	16 / 147 (10.88%)
occurrences all number	17	2	0	0	19
Dysphagia
subjects affected / exposed	5 / 108 (4.63%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	5	1	0	0	6
Gastrooesophageal reflux disease
subjects affected / exposed	13 / 108 (12.04%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	16 / 147 (10.88%)
occurrences all number	14	1	2	0	17
Haemorrhoids
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	0	1	0	2
Nausea
subjects affected / exposed	45 / 108 (41.67%)	7 / 20 (35.00%)	7 / 17 (41.18%)	1 / 2 (50.00%)	60 / 147 (40.82%)
occurrences all number	71	10	7	2	90
Retching
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Stomatitis
subjects affected / exposed	46 / 108 (42.59%)	6 / 20 (30.00%)	3 / 17 (17.65%)	1 / 2 (50.00%)	56 / 147 (38.10%)
occurrences all number	74	10	3	1	88
Vomiting
subjects affected / exposed	35 / 108 (32.41%)	3 / 20 (15.00%)	4 / 17 (23.53%)	0 / 2 (0.00%)	42 / 147 (28.57%)
occurrences all number	55	3	5	0	63
Hepatobiliary disorders
Cholangitis
subjects affected / exposed	3 / 108 (2.78%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	4	1	0	0	5
Hyperbilirubinaemia
subjects affected / exposed	9 / 108 (8.33%)	2 / 20 (10.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	12 / 147 (8.16%)
occurrences all number	9	2	1	0	12
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	64 / 108 (59.26%)	4 / 20 (20.00%)	3 / 17 (17.65%)	2 / 2 (100.00%)	73 / 147 (49.66%)
occurrences all number	66	4	3	2	75
Decubitus ulcer
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	2	1	0	0	3
Dry skin
subjects affected / exposed	30 / 108 (27.78%)	0 / 20 (0.00%)	0 / 17 (0.00%)	2 / 2 (100.00%)	32 / 147 (21.77%)
occurrences all number	33	0	0	2	35
Erythema
subjects affected / exposed	8 / 108 (7.41%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	8 / 147 (5.44%)
occurrences all number	9	0	0	0	9
Hypertrichosis
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	1 / 147 (0.68%)
occurrences all number	0	0	0	1	1
Nail discolouration
subjects affected / exposed	12 / 108 (11.11%)	1 / 20 (5.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	14 / 147 (9.52%)
occurrences all number	12	1	0	1	14
Nail disorder
subjects affected / exposed	6 / 108 (5.56%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	6	0	0	0	6
Nail dystrophy
subjects affected / exposed	11 / 108 (10.19%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	12 / 147 (8.16%)
occurrences all number	14	1	0	0	15
Onychoclasis
subjects affected / exposed	9 / 108 (8.33%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	9 / 147 (6.12%)
occurrences all number	10	0	0	0	10
Onycholysis
subjects affected / exposed	10 / 108 (9.26%)	2 / 20 (10.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	13 / 147 (8.84%)
occurrences all number	10	2	1	0	13
Onychomadesis
subjects affected / exposed	13 / 108 (12.04%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	14 / 147 (9.52%)
occurrences all number	14	1	0	0	15
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	23 / 108 (21.30%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	24 / 147 (16.33%)
occurrences all number	34	2	0	0	36
Pruritus
subjects affected / exposed	13 / 108 (12.04%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	15 / 147 (10.20%)
occurrences all number	15	1	1	0	17
Psoriasis
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	0	1	0	2
Rash
subjects affected / exposed	12 / 108 (11.11%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	13 / 147 (8.84%)
occurrences all number	14	0	1	0	15
Rash maculo-papular
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	2	1	0	0	3
Skin disorder
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Skin exfoliation
subjects affected / exposed	6 / 108 (5.56%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	6	1	0	0	7
Skin fissures
subjects affected / exposed	4 / 108 (3.70%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	5 / 147 (3.40%)
occurrences all number	4	1	0	0	5
Skin mass
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Skin ulcer
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	2	0	0	2
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	5 / 108 (4.63%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	8 / 147 (5.44%)
occurrences all number	6	1	2	0	9
Chronic kidney disease
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	2	1	0	0	3
Dysuria
subjects affected / exposed	2 / 108 (1.85%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	2	2	0	0	4
Haematuria
subjects affected / exposed	0 / 108 (0.00%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	0	2	0	0	2
Micturition urgency
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Pollakiuria
subjects affected / exposed	3 / 108 (2.78%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	4	1	0	0	5
Urinary tract pain
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	2	0	1	0	3
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	37 / 108 (34.26%)	5 / 20 (25.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	44 / 147 (29.93%)
occurrences all number	52	8	3	0	63
Back pain
subjects affected / exposed	27 / 108 (25.00%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	30 / 147 (20.41%)
occurrences all number	34	1	2	0	37
Flank pain
subjects affected / exposed	5 / 108 (4.63%)	2 / 20 (10.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	5	2	0	0	7
Muscle spasms
subjects affected / exposed	11 / 108 (10.19%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	13 / 147 (8.84%)
occurrences all number	12	1	1	0	14
Muscular weakness
subjects affected / exposed	5 / 108 (4.63%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	6	1	0	0	7
Musculoskeletal chest pain
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Musculoskeletal pain
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Myalgia
subjects affected / exposed	15 / 108 (13.89%)	1 / 20 (5.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	18 / 147 (12.24%)
occurrences all number	19	1	2	0	22
Neck pain
subjects affected / exposed	5 / 108 (4.63%)	0 / 20 (0.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	5	0	2	0	7
Osteoporotic fracture
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Pain in extremity
subjects affected / exposed	26 / 108 (24.07%)	3 / 20 (15.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	29 / 147 (19.73%)
occurrences all number	41	4	0	0	45
Infections and infestations
Acinetobacter bacteraemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Bacterial vaginosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Bronchitis
subjects affected / exposed	3 / 108 (2.78%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	3	1	0	0	4
Candida infection
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	0	1	0	2
Cellulitis
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	0	1	1	0	2
Conjunctivitis
subjects affected / exposed	7 / 108 (6.48%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	9 / 147 (6.12%)
occurrences all number	9	1	1	0	11
Cystitis
subjects affected / exposed	5 / 108 (4.63%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	6	1	0	0	7
Device related infection
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Fungal skin infection
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Herpes zoster
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Klebsiella infection
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Nasopharyngitis
subjects affected / exposed	6 / 108 (5.56%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	6 / 147 (4.08%)
occurrences all number	8	0	0	0	8
Oral candidiasis
subjects affected / exposed	5 / 108 (4.63%)	0 / 20 (0.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	6 / 147 (4.08%)
occurrences all number	6	0	0	1	7
Oral herpes
subjects affected / exposed	1 / 108 (0.93%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	0	1	0	2
Paronychia
subjects affected / exposed	9 / 108 (8.33%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	10 / 147 (6.80%)
occurrences all number	9	1	0	0	10
Peritonitis
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Peritonitis bacterial
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Pharyngitis
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	2	1	1	0	4
Pneumonia
subjects affected / exposed	1 / 108 (0.93%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	2 / 147 (1.36%)
occurrences all number	1	1	0	0	2
Rash pustular
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Trichomoniasis
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Upper respiratory tract infection
subjects affected / exposed	7 / 108 (6.48%)	0 / 20 (0.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	8	0	0	0	8
Urinary tract infection
subjects affected / exposed	21 / 108 (19.44%)	2 / 20 (10.00%)	2 / 17 (11.76%)	1 / 2 (50.00%)	26 / 147 (17.69%)
occurrences all number	33	3	2	1	39
Vulvovaginal candidiasis
subjects affected / exposed	0 / 108 (0.00%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	0	1	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	34 / 108 (31.48%)	7 / 20 (35.00%)	7 / 17 (41.18%)	1 / 2 (50.00%)	49 / 147 (33.33%)
occurrences all number	39	10	8	2	59
Dehydration
subjects affected / exposed	16 / 108 (14.81%)	1 / 20 (5.00%)	3 / 17 (17.65%)	1 / 2 (50.00%)	21 / 147 (14.29%)
occurrences all number	17	2	4	1	24
Hypercalcaemia
subjects affected / exposed	16 / 108 (14.81%)	4 / 20 (20.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	21 / 147 (14.29%)
occurrences all number	18	5	2	0	25
Hypercholesterolaemia
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	2	1	0	0	3
Hyperglycaemia
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	3 / 147 (2.04%)
occurrences all number	4	1	0	0	5
Hyperkalaemia
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Hyperphosphataemia
subjects affected / exposed	60 / 108 (55.56%)	13 / 20 (65.00%)	12 / 17 (70.59%)	1 / 2 (50.00%)	86 / 147 (58.50%)
occurrences all number	109	14	13	1	137
Hyperuricaemia
subjects affected / exposed	4 / 108 (3.70%)	3 / 20 (15.00%)	1 / 17 (5.88%)	1 / 2 (50.00%)	9 / 147 (6.12%)
occurrences all number	5	3	1	1	10
Hypoalbuminaemia
subjects affected / exposed	2 / 108 (1.85%)	2 / 20 (10.00%)	3 / 17 (17.65%)	0 / 2 (0.00%)	7 / 147 (4.76%)
occurrences all number	2	2	3	0	7
Hypocalcaemia
subjects affected / exposed	2 / 108 (1.85%)	1 / 20 (5.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	4 / 147 (2.72%)
occurrences all number	3	1	1	0	5
Hypokalaemia
subjects affected / exposed	9 / 108 (8.33%)	0 / 20 (0.00%)	1 / 17 (5.88%)	0 / 2 (0.00%)	10 / 147 (6.80%)
occurrences all number	10	0	1	0	11
Hyponatraemia
subjects affected / exposed	6 / 108 (5.56%)	4 / 20 (20.00%)	4 / 17 (23.53%)	0 / 2 (0.00%)	14 / 147 (9.52%)
occurrences all number	10	6	6	0	22
Hypophosphataemia
subjects affected / exposed	28 / 108 (25.93%)	4 / 20 (20.00%)	2 / 17 (11.76%)	0 / 2 (0.00%)	34 / 147 (23.13%)
occurrences all number	49	6	2	0	57
Hypovitaminosis
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Malnutrition
subjects affected / exposed	0 / 108 (0.00%)	1 / 20 (5.00%)	0 / 17 (0.00%)	0 / 2 (0.00%)	1 / 147 (0.68%)
occurrences all number	0	1	0	0	1
Vitamin D deficiency
subjects affected / exposed	10 / 108 (9.26%)	1 / 20 (5.00%)	0 / 17 (0.00%)	1 / 2 (50.00%)	12 / 147 (8.16%)
occurrences all number	10	1	0	1	12

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

14 Sep 2016

The primary purpose of this amendment was to amend the language regarding participants to whom the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-BIL21 was to be administered.

05 Dec 2016

The primary purpose of this amendment was to update language based on Regulatory Agencies comments. Updates included but were not limited to clarification of inclusion and exclusion criteria, the addition of updated clinical experience data, and guidance for dose reductions.

18 Jan 2017

The primary purpose of this amendment was to update the text in the Protocol based on the European Union Voluntary Harmonisation Procedure (VHP) request, to clarify requirements for human immunodeficiency virus (HIV) screening and enrollment parameters for Cohort C.

21 Mar 2017

The primary purpose of this amendment was to provide new language to allow participants to enroll under local genomic testing results. Updated clinical experience data were added as well.

03 Oct 2017

The primary purpose of this amendment was to increase the total number of participants enrolled into the study.

15 Feb 2018

The primary purpose of this amendment was to ensure the study population was clearly identified, to provide guidelines for dose reductions, and to provide additional language for ophthalmologic testing and hyperphosphatemia grading.

02 Apr 2020

The primary purpose of this amendment was to incorporate previous administrative changes and include updated language for comprehensive eye examination, per Food and Drug Administration (FDA) feedback.

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.

None reported

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 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of INCB054828 in Subjects With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Including FGFR2 Translocations Who Failed Previous Therapy

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Objective response rate (ORR) in participants with FGFR2 rearrangements or fusions

Primary: Objective response rate (ORR) in participants with FGFR2 rearrangements or fusions

Secondary: ORR in participants FGF/FGFR alterations other than FGFR2 rearrangements or fusions

Secondary: ORR in participants FGF/FGFR alterations other than FGFR2 rearrangements or fusions

Secondary: ORR in all participants with FGF/FGFR alterations

Secondary: ORR in all participants with FGF/FGFR alterations

Secondary: ORR in participants negative for FGF/FGFR alterations

Secondary: ORR in participants negative for FGF/FGFR alterations

Secondary: Progression-free survival (PFS)

Secondary: Progression-free survival (PFS)

Secondary: Duration of response (DOR)

Secondary: Duration of response (DOR)

Secondary: Disease control rate (DCR)

Secondary: Disease control rate (DCR)

Secondary: Overall survival

Secondary: Overall survival

Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

Secondary: Number of participants with any treatment-emergent adverse event (TEAE)

Secondary: First-order absorption rate constant (ka) of pemigatinib

Secondary: First-order absorption rate constant (ka) of pemigatinib

Secondary: CL/F of pemigatinib

Secondary: CL/F of pemigatinib

Secondary: Vc/F of pemigatinib

Secondary: Vc/F of pemigatinib

Secondary: Vp/F of pemigatinib

Secondary: Vp/F of pemigatinib

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 2, Open-Label, Single-Arm, Multicenter Study to Evaluate the Efficacy and Safety of INCB054828 in Subjects With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Including FGFR2 Translocations Who Failed Previous Therapy