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Clinical Trial Results:
A Phase I/II, multicenter, open-label study of oral FGF401 in adult patients with hepatocellular carcinoma or solid malignancies characterized by positive FGFR4 and KLB expression Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.

Summary
EudraCT number	2014-002929-35
Trial protocol	ES DE FR
Global end of trial date	30 May 2019

Results information
Results version number	v1(current)
This version publication date	14 Jun 2020
First version publication date	14 Jun 2020
Other versions

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

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Trial information

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Sponsor protocol code

CFGF401X2101

ISRCTN number

US NCT number

NCT02325739

WHO universal trial number (UTN)

Sponsor organisation name

Novartis Pharma, AG

Sponsor organisation address

CH-4002, 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

30 May 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

30 May 2019

Was the trial ended prematurely?

Main objective of the trial

Phase I part: To estimate the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) of FGF401 single agent and in combination with PDR001. Phase II part: To investigate the anti-tumor activity of FGF401 single agent and in combination with PDR001.

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

29 Dec 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

France: 46

Country: Number of subjects enrolled

China: 1

Country: Number of subjects enrolled

Germany: 24

Country: Number of subjects enrolled

Hong Kong: 22

Country: Number of subjects enrolled

Italy: 5

Country: Number of subjects enrolled

Japan: 11

Country: Number of subjects enrolled

Korea, Republic of: 19

Country: Number of subjects enrolled

Singapore: 9

Country: Number of subjects enrolled

Spain: 9

Country: Number of subjects enrolled

Taiwan: 19

Country: Number of subjects enrolled

United States: 7

Worldwide total number of subjects

172

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)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

160 subjects were enrolled & treated with FGF401 single agent. In the Phase I part 74 subjects & 86 subjects in the Phase II part. 12 subjects were treated in the Phase I of the combination of FGF401 and PDR001. All subjects completed the study as per protocol & reasons for discontinuation of treatment are provided in the 'Not Completed' section.

Screening details

At least 21 evaluable subjects were to be treated in Phase I for the model to have reasonable operating characteristics relating to its MTD &/or RP2D. Each group in the Phase II dose expansion targeted a different number of subjects. Group 1 & Group 2 planned to enroll around 40 subjects each & Group 3 planned to enroll approximately 20 subjects.

Period 1 title

Phase I and Phase II (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase I: 50 mg Fasted

Arm description

Participants received 50 mg of FGF401 while fasted

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase I: 80 mg Fasted

Arm description

Participants received 80 mg of FGF401 while fasted

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase I: 80 mg Fed

Arm description

Participants received 80 mg of FGF401 while fed.

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase I: 120 mg Fasted

Arm description

Participants received 120 mg of FGF401 while fasted

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase I: 120 mg Fed

Arm description

Participants received 120 mg of FGF401 while fed.

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase I: 150 mg Fasted

Arm description

Participants received 150 mg of FGF401 while fasted.

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase I: FGF401 80 mg + PDR001 300 mg

Arm description

Participants received 80 mg of FGF401 and 300 mg of PDR001 while fasted.

Arm type

Experimental

Investigational medicinal product name

PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 was taken every three weeks (3QW)

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase I: FGF401 120 mg + PDR001 300 mg

Arm description

Participants received 120 mg of FGF401 and 300mg of PDR001 while fasted

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Investigational medicinal product name

PDR001

Investigational medicinal product code

Other name

Pharmaceutical forms

Infusion

Routes of administration

Intravenous use

Dosage and administration details

PDR001 was taken every three weeks (3QW)

Phase II: Group 1

Arm description

Group 1 comprised of HCC participants from Asian countries

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase II: Group 2

Arm description

HCC subjects from non-Asian countries

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Phase II: Group 3

Arm description

Subjects with other solid malignancies regardless of geography

Arm type

Experimental

Investigational medicinal product name

FGF401

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

FGF401 was taken on a flat scale of mg/day once daily (QD) on a continuous dosing regimen or the combination of FGF401 on a continuous once daily dosing regimen.

Number of subjects in period 1	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg	Phase II: Group 1	Phase II: Group 2	Phase II: Group 3
Started	11	6	5	26	19	7	6	6	30	36	20
Completed	0	0	0	0	0	0	0	0	0	0	0
Not completed	11	6	5	26	19	7	6	6	30	36	20
Adverse event, serious fatal	-	-	-	-	2	-	-	-	-	-	-
Physician decision	-	-	-	-	-	-	-	-	-	1	-
Adverse event, non-fatal	1	-	1	2	3	1	-	2	4	5	1
Progressive disease	9	6	3	23	14	6	6	3	22	29	18
Subject/guardian decision	1	-	1	1	-	-	-	1	4	1	1

Baseline characteristics

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Reporting group title

Phase I: 50 mg Fasted

Reporting group description

Participants received 50 mg of FGF401 while fasted

Reporting group title

Phase I: 80 mg Fasted

Reporting group description

Participants received 80 mg of FGF401 while fasted

Reporting group title

Phase I: 80 mg Fed

Reporting group description

Participants received 80 mg of FGF401 while fed.

Reporting group title

Phase I: 120 mg Fasted

Reporting group description

Participants received 120 mg of FGF401 while fasted

Reporting group title

Phase I: 120 mg Fed

Reporting group description

Participants received 120 mg of FGF401 while fed.

Reporting group title

Phase I: 150 mg Fasted

Reporting group description

Participants received 150 mg of FGF401 while fasted.

Reporting group title

Phase I: FGF401 80 mg + PDR001 300 mg

Reporting group description

Participants received 80 mg of FGF401 and 300 mg of PDR001 while fasted.

Reporting group title

Phase I: FGF401 120 mg + PDR001 300 mg

Reporting group description

Participants received 120 mg of FGF401 and 300mg of PDR001 while fasted

Reporting group title

Phase II: Group 1

Reporting group description

Group 1 comprised of HCC participants from Asian countries

Reporting group title

Phase II: Group 2

Reporting group description

HCC subjects from non-Asian countries

Reporting group title

Phase II: Group 3

Reporting group description

Subjects with other solid malignancies regardless of geography

Reporting group values	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg	Phase II: Group 1	Phase II: Group 2	Phase II: Group 3	Total
Number of subjects	11	6	5	26	19	7	6	6	30	36	20	172
Age Categorical
Units: participants
18 y - <65 y	6	4	3	14	12	4	3	3	22	15	10	96
65 y - <85 y	5	2	2	12	6	3	3	3	8	21	10	75
>=85 y	0	0	0	0	1	0	0	0	0	0	0	1
Sex: Female, Male
Units: participants
Female	4	1	1	3	6	0	1	4	8	7	12	47
Male	7	5	4	23	13	7	5	2	22	29	8	125
Race/Ethnicity, Customized
Units: Subjects
Asian	9	2	2	14	10	4	3	5	30	0	2	81
Black	0	0	0	0	1	1	0	0	0	0	0	2
Caucasian	2	4	3	12	8	1	3	1	0	21	11	66
Not applicable	0	0	0	0	0	0	0	0	0	1	0	1
Other	0	0	0	0	0	0	0	0	0	1	0	1
Pacific Islander	0	0	0	0	0	0	0	0	0	1	0	1
Unknown	0	0	0	0	0	1	0	0	0	12	7	20

End points

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Reporting group title

Phase I: 50 mg Fasted

Reporting group description

Participants received 50 mg of FGF401 while fasted

Reporting group title

Phase I: 80 mg Fasted

Reporting group description

Participants received 80 mg of FGF401 while fasted

Reporting group title

Phase I: 80 mg Fed

Reporting group description

Participants received 80 mg of FGF401 while fed.

Reporting group title

Phase I: 120 mg Fasted

Reporting group description

Participants received 120 mg of FGF401 while fasted

Reporting group title

Phase I: 120 mg Fed

Reporting group description

Participants received 120 mg of FGF401 while fed.

Reporting group title

Phase I: 150 mg Fasted

Reporting group description

Participants received 150 mg of FGF401 while fasted.

Reporting group title

Phase I: FGF401 80 mg + PDR001 300 mg

Reporting group description

Participants received 80 mg of FGF401 and 300 mg of PDR001 while fasted.

Reporting group title

Phase I: FGF401 120 mg + PDR001 300 mg

Reporting group description

Participants received 120 mg of FGF401 and 300mg of PDR001 while fasted

Reporting group title

Phase II: Group 1

Reporting group description

Group 1 comprised of HCC participants from Asian countries

Reporting group title

Phase II: Group 2

Reporting group description

HCC subjects from non-Asian countries

Reporting group title

Phase II: Group 3

Reporting group description

Subjects with other solid malignancies regardless of geography

Primary: Incidence rate of Dose-limiting Toxicity (DLT): Phase I only

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End point title

Incidence rate of Dose-limiting Toxicity (DLT): Phase I only ^[1] ^[2]

End point description

A dose-limiting toxicity was defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurred within the evaluation period of DLTs and met any of the criteria listed. The estimation of the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of the treatment was based upon the estimation of the probability of DLT during the evaluation period for subjects in the dose determining set (DDS). A subject with multiple occurrences of a DLT under one treatment is counted only once in the AE category for that treatment. A subject with multiple DLTs within a primary system organ class is counted only once in the total row.

End point type

Primary

End point timeframe

Cycle 1 (C1) (21 days) for FGF401 single agent, Cycle 1 and Cycle 2 (C2) (42 days) for FGF401 and PDR001 combination

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 analysis was planned for this endpoint
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg
Number of subjects analysed	10	6	5	23	18	7	6	6
Units: Percentage of DLTs
number (not applicable)
Any Primary system organ class (SOC)	10.0	0	0	4.3	5.6	42.9	0	0
Invest.: Aspartate Aminotrans. increased	0	0	0	4.3	0	42.9	0	0
Invest.: Alanine aminotrans. increased	10.0	0	0	0	0	14.3	0	0
Invest.: Blood bilirubin increased	0	0	0	0	5.6	0	0	0

No statistical analyses for this end point

Primary: Time to progression (TTP): Group 1 & Group 2 (Phase II only)

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End point title

Time to progression (TTP): Group 1 & Group 2 (Phase II only) ^[3] ^[4]

End point description

TTP is defined as the date of start treatment to the date of event defined as the first documented progression or death due to underlying cancer. Method used was Kaplan-Meier analysis. Group 1: HCC subjects form Asian countries Group 2: HCC subjects form non-Asian countries

End point type

Primary

End point timeframe

5 years

Notes
[3] - 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 analysis was planned for this endpoint
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase II: Group 1	Phase II: Group 2
Number of subjects analysed	30	36
Units: months
median (confidence interval 90%)	2.6 (1.3 to 999)	3.9 (2.9 to 999)

No statistical analyses for this end point

Primary: Overall response rate (ORR) based on local assessment: Group 3 (Phase II only)

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End point title

Overall response rate (ORR) based on local assessment: Group 3 (Phase II only) ^[5] ^[6]

End point description

ORR is defined as the percentage of patients with a best overall response of CR or PR (RECIST v1.1). FGF401 single agent-Phase II part - Group 3 (non-HCC, other solid tumors).

End point type

Primary

End point timeframe

5 years

Notes
[5] - 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 analysis was planned for this endpoint
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase II: Group 3
Number of subjects analysed	20
Units: Percentage of participants
number (confidence interval 95%)	0 (0.0 to 16.8)

No statistical analyses for this end point

Secondary: Best Overall Response (BOR) by Investigator assessment: Phase I and Phase II

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End point title

Best Overall Response (BOR) by Investigator assessment: Phase I and Phase II

End point description

BOR is the best response recorded from the start of the treatment until disease progression/recurrence. BOR is determined according to: complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) and unknown.

End point type

Secondary

End point timeframe

5 years

End point values	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg	Phase II: Group 1	Phase II: Group 2	Phase II: Group 3
Number of subjects analysed	11	6	5	26	19	7	6	6	30	36	20
Units: participants
Complete Response	0	0	0	1	0	0	0	0	0	0	0
Partial Response	0	1	1	0	0	1	1	1	2	2	0
Stable Disease	2	1	2	12	9	4	2	2	11	20	6
Progressive Disease	7	4	1	11	8	2	3	1	16	6	12
Unknown	2	0	1	2	2	0	0	2	1	8	2

No statistical analyses for this end point

Secondary: Overall Response Rate (ORR) by Investigator assessment Phase I and FGF401 single agent Phase II Groups 1 & 2

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End point title

Overall Response Rate (ORR) by Investigator assessment Phase I and FGF401 single agent Phase II Groups 1 & 2

End point description

ORR is defined as the proportion of patients with a best overall response of CR or PR (RECIST v1.1). Phase I part and FGF401 single agent Phase II Group 1 (HCC, Asians) and Group 2 (HCC, non-Asians)

End point type

Secondary

End point timeframe

5 years

End point values	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg	Phase II: Group 1	Phase II: Group 2	Phase II: Group 3
Number of subjects analysed	11	6	5	26	19	7	6	6	30	36	0 ^[7]
Units: Percentage of participants
number (confidence interval 95%)	0 (0.0 to 28.5)	16.7 (0.4 to 64.1)	20.0 (0.5 to 71.6)	3.8 (0.1 to 19.6)	0 (0.0 to 17.6)	14.3 (0.4 to 57.9)	16.7 (0.4 to 64.1)	16.7 (0.4 to 64.1)	6.7 (0.8 to 22.1)	5.6 (0.7 to 18.7)	( to )

Notes
[7] - This arm was not analyzed for this endpoint.

No statistical analyses for this end point

Secondary: Disease Control Rate (DCR) by local Investigator assessment Phase I and FGF401 single agent Phase II Groups 1, 2 & 3

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End point title

Disease Control Rate (DCR) by local Investigator assessment Phase I and FGF401 single agent Phase II Groups 1, 2 & 3

End point description

DCR is the percentage of participants with a best overall response of CR or PR or SD per local assessment according to RECIST v1.1. Phase I part and FGF401 single agent Phase II Group 1 (HCC, Asians) and Group 2 (HCC, non-Asians) and Group 3 (non-HCC, other solid tumors).

End point type

Secondary

End point timeframe

5 years

End point values	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg	Phase II: Group 1	Phase II: Group 2	Phase II: Group 3
Number of subjects analysed	11	6	5	26	19	7	6	6	30	36	20
Units: percentage of participants
number (confidence interval 95%)	18.2 (2.3 to 51.8)	33.3 (4.3 to 77.7)	60.0 (14.7 to 94.7)	50.0 (29.9 to 70.1)	47.4 (24.4 to 71.1)	71.4 (29.0 to 96.3)	50.0 (11.8 to 88.2)	50.0 (11.8 to 88.2)	43.3 (25.5 to 62.6)	61.1 (43.5 to 76.9)	30.0 (11.9 to 54.3)

No statistical analyses for this end point

Secondary: Time to Progression (TTP) - Phase I (single agent FGF401 & in combination with PDR001) dosed at RP2D

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End point title

Time to Progression (TTP) - Phase I (single agent FGF401 & in combination with PDR001) dosed at RP2D ^[8]

End point description

TTP is defined as the date of start treatment to the date of event defined as the first documented progression or death due to underlying cancer. Method used was Kaplan-Meier analysis.

End point type

Secondary

End point timeframe

5 years

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: FGF401 120 mg + PDR001 300 mg
Number of subjects analysed	26	19	6
Units: months
median (confidence interval 90%)	4.1 (1.6 to 999)	2.0 (1.4 to 999)	5.3 (3.0 to 999)

No statistical analyses for this end point

Secondary: Overall Survival (OS) - Phase I (single agent & combination) dosed at RP2D and Phase II FGF401 single agent

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End point title

Overall Survival (OS) - Phase I (single agent & combination) dosed at RP2D and Phase II FGF401 single agent ^[9]

End point description

Overall survival (OS) is defined as the time from date of start of treatment to date of death due to any cause. If a patient was not known to have died, survival was censored at the date of last known date patient alive. Method used was Kaplan-Meier analysis.

End point type

Secondary

End point timeframe

start of treatment to death, up to about 53 months

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: FGF401 120 mg + PDR001 300 mg	Phase II: Group 1	Phase II: Group 2	Phase II: Group 3
Number of subjects analysed	26	19	6	30	36	20
Units: months
median (confidence interval 90%)	7.0 (5.1 to 999)	4.9 (2.6 to 999)	999 (999 to 999)	5.9 (5.1 to 999)	10.9 (7.9 to 999)	6.2 (4.2 to 999)

No statistical analyses for this end point

Secondary: Progression-free Survival (PFS) - FGF401 single agent Phase II: Group 3

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End point title

Progression-free Survival (PFS) - FGF401 single agent Phase II: Group 3 ^[10]

End point description

Progression-free survival (PFS) is the time from date of start of treatment to the date of event defined as the first documented progression or death due to any cause. If a patient has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Group 3 - non-HCC, other solid tumors. Method used was Kaplan-Meier analysis.

End point type

Secondary

End point timeframe

5 years

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase II: Group 3
Number of subjects analysed	20
Units: months
median (confidence interval 95%)	1.4 (1.4 to 2.8)

No statistical analyses for this end point

Secondary: Presence and/or concentration of anti-PDR001 antibodies

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End point title

Presence and/or concentration of anti-PDR001 antibodies ^[11]

End point description

Serum PDR001 concentrations as well as immunogenicity analysis were performed for all subjects receiving PDR001. Treatment-induced ADA-positive percentage was based on percentage subjects ADA-negative at baseline. Treatment-boosted ADA-positive percentage was based on subjects ADA-positive at baseline.

End point type

Secondary

End point timeframe

Day 1 of Cycle 1 to 6, approx. 10 months after C1D1 and 150-day safety ollow up (FU)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg
Number of subjects analysed	6	6
Units: percentage of participants
number (not applicable)
ADA-negative	100.0	83.3
ADA-positive (i.e. ADA incidence)	0	16.7
Treatment-induced ADA-positive	0	20.0
Treatment-boosted ADA-positive	0	0

No statistical analyses for this end point

Secondary: Cmax of PDR001 in combination with FGF401: Phase I

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End point title

Cmax of PDR001 in combination with FGF401: Phase I ^[12]

End point description

Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)

End point type

Secondary

End point timeframe

After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg
Number of subjects analysed	6	6
Units: μg/mL
geometric mean (geometric coefficient of variation)	74.7 ( 43.0 )	87.7 ( 5.4 )

No statistical analyses for this end point

Secondary: AUClast and AUCtau of PDR001 in combination with FGF401: Phase I

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End point title

AUClast and AUCtau of PDR001 in combination with FGF401: Phase I ^[13]

End point description

AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) AUCtau: The AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1)

End point type

Secondary

End point timeframe

After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg
Number of subjects analysed	6	6
Units: day*μg/mL
geometric mean (geometric coefficient of variation)
AUClast	795 ( 34.5 )	978 ( 15.8 )
AUC0-504h (n = 3, 6)	760 ( 1.9 )	967 ( 13.9 )

No statistical analyses for this end point

Secondary: T1/2 of PDR001: Phase I

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End point title

T1/2 of PDR001: Phase I ^[14]

End point description

Due to the sparse PK sampling designed from PDR001, the PDR001 concentration data was insufficient for accurate estimation of secondary PK parameters including T1/2 which were considered not reportable

End point type

Secondary

End point timeframe

After the first dosing sample collection was at: C1D1 0hr , C1D1 1hr, C1D8 168hr, C1D15 336hr, C2D1 504hr; each cycle is 21 days

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg
Number of subjects analysed	0 ^[15]	0 ^[16]
Units: hour (hr)
arithmetic mean (standard deviation)	( )	( )

Notes
[15] - This endpoint was not analyzed
[16] - This endpoint was not analyzed

No statistical analyses for this end point

Secondary: Cmax of FGF401: Phase I

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End point title

Cmax of FGF401: Phase I ^[17]

End point description

Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)

End point type

Secondary

End point timeframe

Cycle 1 Day 1 & Day 8, Cycle 2 Day 1 (each cycle is 21 days)

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted
Number of subjects analysed	10	6	5	26	19	7
Units: ng/mL
geometric mean (geometric coefficient of variation)
Cycle 1 Day 1 (n=6, 5, 5, 26, 19,7)	698 ( 36.1 )	967 ( 25.0 )	659 ( 15.2 )	1090 ( 37.9 )	1050 ( 32.3 )	1400 ( 32.1 )
Cycle 1 Day 8 (7, 6, 4, 24, 18, 6)	663 ( 46.8 )	838 ( 16.5 )	704 ( 22.1 )	1120 ( 36.5 )	1060 ( 22.1 )	1070 ( 46.0 )
Cycle 2 Day 1 (n = 9, 6, 5, 22, 17, 4)	696 ( 44.2 )	786 ( 25.5 )	703 ( 41.7 )	1070 ( 32.2 )	1000 ( 23.9 )	1350 ( 28.1 )

No statistical analyses for this end point

Secondary: Cmax of FGF401 in combination with PDR001: Phase I

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End point title

Cmax of FGF401 in combination with PDR001: Phase I ^[18]

End point description

Cmax is the maximum (peak) observed plasma drug concentration (mass x volume-1)

End point type

Secondary

End point timeframe

Cycle 1 Day 1

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg
Number of subjects analysed	6	6
Units: ng/mL
geometric mean (geometric coefficient of variation)	732 ( 26.8 )	1450 ( 31.4 )

No statistical analyses for this end point

Secondary: AUCinf, AUClast & AUCtau of FGF401: Phase I

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End point title

AUCinf, AUClast & AUCtau of FGF401: Phase I ^[19]

End point description

AUCinf: The AUC from time zero to infinity (mass x time x volume-1) AUClast: The AUC from time zero to the last measurable concentration sampling time (tlast) (mass x time x volume-1) AUCtau: The AUC calculated to the end of a dosing interval (tau) (amount x time x volume-1)

End point type

Secondary

End point timeframe

Cycle 1 Day 1 & Day 8, Cycle 2 Day 1 (each cycle is 21 days)

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted
Number of subjects analysed	10	6	5	26	19	7
Units: hr*ng/mL
geometric mean (geometric coefficient of variation)
AUCinf C1D1 (n = 6, 5, 4, 24, 17,7)	4920 ( 51.9 )	5090 ( 32.9 )	5560 ( 23.1 )	7210 ( 35.4 )	8520 ( 35.2 )	8190 ( 42.7 )
AUClast C1D1 (n =6, 5, 5, 26, 19, 7)	4610 ( 50.4 )	4710 ( 38.0 )	4600 ( 39.2 )	6710 ( 35.6 )	7850 ( 34.1 )	7920 ( 42.0 )
AUCtau C1D1 (n = 6, 5, 5, 26, 18, 7)	4610 ( 50.4 )	4910 ( 30.3 )	4860 ( 29.4 )	6840 ( 33.6 )	8020 ( 33.5 )	7930 ( 41.8 )
AUCinf C1D8 (n = 6, 6, 4, 18, 15, 6)	3650 ( 71.9 )	5130 ( 28.9 )	5550 ( 23.2 )	7590 ( 43.0 )	7980 ( 25.1 )	7850 ( 29.4 )
AUClast C1D8 (n = 6, 6, 4, 24, 18, 6)	3460 ( 62.5 )	4840 ( 27.0 )	5280 ( 23.9 )	6480 ( 47.5 )	7640 ( 33.1 )	7550 ( 28.6 )
AUCtau C1D8 (n = 7, 6, 4, 24, 16, 6)	3650 ( 65.6 )	4850 ( 27.0 )	5290 ( 24.0 )	6970 ( 38.7 )	7330 ( 26.7 )	7510 ( 29.8 )
AUCinf C2D1 (n = 9, 6, 5, 22, 13, 4)	4390 ( 54.0 )	4580 ( 30.6 )	5110 ( 44.3 )	7770 ( 33.2 )	8760 ( 23.5 )	7850 ( 25.7 )
AUClast C2D1 (n = 9, 6, 5, 22, 17, 4)	4100 ( 52.9 )	4210 ( 32.5 )	4880 ( 43.1 )	7260 ( 33.6 )	7520 ( 38.7 )	7610 ( 25.8 )
AUCtau C2D1 (n = 9, 6, 5, 22, 15, 4)	4100 ( 52.7 )	4360 ( 28.5 )	4870 ( 43.7 )	7330 ( 31.7 )	7830 ( 23.4 )	7620 ( 25.7 )

No statistical analyses for this end point

Secondary: AUCinf, AUClast & AUCtau of FGF401 in combination with PDR001: Phase I

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End point title

AUCinf, AUClast & AUCtau of FGF401 in combination with PDR001: Phase I ^[20]

End point description

End point type

Secondary

End point timeframe

Cycle 1 Day 1

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: FGF401 80 mg + PDR001 300 mg	Phase I: FGF401 120 mg + PDR001 300 mg
Number of subjects analysed	6	6
Units: hr*ng/mL
geometric mean (geometric coefficient of variation)
AUCinf	5030 ( 25.5 )	7540 ( 37.0 )
AUClast	4760 ( 25.0 )	7280 ( 36.7 )
AUCtau	4770 ( 24.4 )	7280 ( 36.7 )

No statistical analyses for this end point

Secondary: T1/2 of FGF401: Phase I

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End point title

T1/2 of FGF401: Phase I ^[21]

End point description

The elimination half-life associated with the terminal slope ( z) of a semi logarithmic concentration-time curve (time).

End point type

Secondary

End point timeframe

Cycle 1 Day 1 & Day 8, Cycle 2 Day 1 (each cycle is 21 days)

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: No statistical analysis was planned for this endpoint

End point values	Phase I: 50 mg Fasted	Phase I: 80 mg Fasted	Phase I: 80 mg Fed	Phase I: 120 mg Fasted	Phase I: 120 mg Fed	Phase I: 150 mg Fasted
Number of subjects analysed	10	6	5	26	19	7
Units: hour (hr)
geometric mean (geometric coefficient of variation)
C1D1 (n = 6, 5, 4, 24, 17, 7)	6.27 ( 16.2 )	4.91 ( 31.6 )	5.2 ( 8.8 )	5.47 ( 14.4 )	5.16 ( 16.3 )	5 ( 11.3 )
C1D8 (n = 6, 6, 4, 18, 15, 6)	6.57 ( 16.6 )	6.08 ( 13.8 )	5.58 ( 12.0 )	5.43 ( 30.0 )	5.58 ( 17.1 )	5.24 ( 12.4 )
C2D1 (n = 9, 6, 5, 22, 13, 4)	6.46 ( 18.9 )	5.44 ( 34.9 )	5.43 ( 17.2 )	5.8 ( 22.1 )	5.81 ( 20.2 )	4.92 ( 14.4 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

.Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse events are reported in this record from First Patient First Treatment until Last Patient Last Visit.

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

21.1

Reporting group title

Phase I Part 50 mg Fasted

Reporting group description

Participants received 50 mg of FGF401 while fasted

Reporting group title

Phase I Part 80 mg Fasted

Reporting group description

Participants received 80 mg of FGF401 while fasted

Reporting group title

Phase I Part 80 mg Fed

Reporting group description

Participants received 80 mg of FGF401 while fed

Reporting group title

Phase I Part 120 mg Fasted

Reporting group description

Participants received 120 mg of FGF401 while fasted

Reporting group title

Phase I Part 120 mg Fed

Reporting group description

Participants received 120 mg of FGF401 while fed

Reporting group title

Phase I Part 150 mg Fasted

Reporting group description

Participants received 150 mg of FGF401 while fasted

Reporting group title

Phase II Part Group 1

Reporting group description

This group is comprised of HCC participants from Asian countries who received the RP2D of FGF401 while fasted

Reporting group title

Phase II Part Group 2

Reporting group description

This group is comprised of HCC participants from non- Asian countries who received the RP2D of FGF401 while fasted

Reporting group title

Phase II Part Group 3

Reporting group description

This group comprised of participants with other solid malignancies regardless of geography who received the RP2D of FGF401 while fasted

Reporting group title

All Patients Single agent

Reporting group description

This group comprised of all participants who took single agent FGF401

Reporting group title

Phase I Part FGF401 80 mg + PDR001 300 mg

Reporting group description

Participants received 80 mg of FGF401 and 300 mg of PDR001 while fasted.

Reporting group title

Phase I Part FGF401 120 mg + PDR001 300 mg

Reporting group description

Participants received 120 mg of FGF402 and 300 mg of PDR001 while fasted

Reporting group title

All Patients Combination

Reporting group description

This group comprised of all participants who took combination treatment of FGF401 and PDR001

Reporting group title

All Patients

Reporting group description

These are all the participants in the study

Phase I Part 50 mg Fasted

Phase I Part 80 mg Fasted

Phase I Part 80 mg Fed

Phase I Part 120 mg Fasted

Phase I Part 120 mg Fed

Phase I Part 150 mg Fasted

Phase II Part Group 1

Phase II Part Group 2

Phase II Part Group 3

All Patients Single agent

Phase I Part FGF401 80 mg + PDR001 300 mg

Phase I Part FGF401 120 mg + PDR001 300 mg

All Patients Combination

All Patients

Total subjects affected by serious adverse events

subjects affected / exposed

3 / 11 (27.27%)

5 / 6 (83.33%)

3 / 5 (60.00%)

15 / 26 (57.69%)

9 / 19 (47.37%)

3 / 7 (42.86%)

15 / 30 (50.00%)

9 / 36 (25.00%)

8 / 20 (40.00%)

70 / 160 (43.75%)

0 / 6 (0.00%)

2 / 6 (33.33%)

2 / 12 (16.67%)

72 / 172 (41.86%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Liver carcinoma ruptured

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

1 / 36 (2.78%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

1 / 6 (16.67%)

1 / 12 (8.33%)

2 / 172 (1.16%)

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

Tumour associated fever

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

1 / 7 (14.29%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Tumour thrombosis

subjects affected / exposed

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Vascular disorders

Aneurysm

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

1 / 36 (2.78%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Bleeding varicose vein

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Hypovolaemic shock

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

1 / 36 (2.78%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Inferior vena caval occlusion

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Venous thrombosis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

General disorders and administration site conditions

Asthenia

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Chest discomfort

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Fatigue

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

1 / 19 (5.26%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Gait disturbance

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Multiple organ dysfunction syndrome

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

1 / 36 (2.78%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Oedema peripheral

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Pyrexia

subjects affected / exposed

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

2 / 20 (10.00%)

3 / 160 (1.88%)

0 / 6 (0.00%)

2 / 6 (33.33%)

2 / 12 (16.67%)

5 / 172 (2.91%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 3

0 / 4

0 / 0

0 / 2

0 / 6

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Atelectasis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Bronchial obstruction

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Bronchostenosis

subjects affected / exposed

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

1 / 19 (5.26%)

1 / 7 (14.29%)

1 / 30 (3.33%)

0 / 36 (0.00%)

1 / 20 (5.00%)

4 / 160 (2.50%)

0 / 6 (0.00%)

0 / 12 (0.00%)

4 / 172 (2.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 4

0 / 0

0 / 4

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

2 / 26 (7.69%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Pneumonitis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Productive cough

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

1 / 19 (5.26%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Psychiatric disorders

Confusional state

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

1 / 7 (14.29%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

2 / 2

0 / 0

2 / 2

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

2 / 7 (28.57%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

3 / 160 (1.88%)

0 / 6 (0.00%)

0 / 12 (0.00%)

3 / 172 (1.74%)

occurrences causally related to treatment / all

0 / 0

2 / 2

1 / 1

0 / 0

3 / 3

0 / 0

3 / 3

deaths causally related to treatment / all

0 / 0

Blood bilirubin increased

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 2

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Bone contusion

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

1 / 19 (5.26%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Acute coronary syndrome

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Coronary artery disease

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

1 / 19 (5.26%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Nervous system disorders

Carotid artery stenosis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Cerebrovascular accident

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Dysarthria

subjects affected / exposed

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Haemorrhage intracranial

subjects affected / exposed

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Paraesthesia

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Paraparesis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Paraplegia

subjects affected / exposed

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

1 / 19 (5.26%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Ear and labyrinth disorders

Vertigo

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Gastrointestinal disorders

Abdominal distension

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

0 / 1

0 / 0

0 / 5

0 / 0

0 / 5

deaths causally related to treatment / all

0 / 0

Abdominal pain

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 26 (0.00%)

3 / 19 (15.79%)

0 / 7 (0.00%)

0 / 30 (0.00%)

2 / 36 (5.56%)

3 / 20 (15.00%)

9 / 160 (5.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

9 / 172 (5.23%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 2

0 / 3

0 / 9

0 / 0

0 / 9

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

1 / 19 (5.26%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

3 / 160 (1.88%)

0 / 6 (0.00%)

0 / 12 (0.00%)

3 / 172 (1.74%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

1 / 11 (9.09%)

0 / 6 (0.00%)

1 / 5 (20.00%)

2 / 26 (7.69%)

1 / 19 (5.26%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

5 / 160 (3.13%)

0 / 6 (0.00%)

0 / 12 (0.00%)

5 / 172 (2.91%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 2

0 / 1

0 / 0

0 / 5

0 / 0

0 / 5

deaths causally related to treatment / all

0 / 0

Diarrhoea

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

2 / 6 (33.33%)

2 / 12 (16.67%)

3 / 172 (1.74%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

1 / 1

0 / 0

1 / 2

2 / 3

deaths causally related to treatment / all

0 / 0

Duodenal obstruction

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Dysphagia

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastric varices

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

Gastritis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

2 / 26 (7.69%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

1 / 19 (5.26%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Haematemesis

subjects affected / exposed

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

1 / 36 (2.78%)

0 / 20 (0.00%)

3 / 160 (1.88%)

0 / 6 (0.00%)

0 / 12 (0.00%)

3 / 172 (1.74%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Oesophageal varices haemorrhage

subjects affected / exposed

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

1 / 7 (14.29%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

1 / 6 (16.67%)

1 / 12 (8.33%)

3 / 172 (1.74%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 1

0 / 3

deaths causally related to treatment / all

0 / 0

Upper gastrointestinal haemorrhage

subjects affected / exposed

1 / 11 (9.09%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 26 (0.00%)

1 / 19 (5.26%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

3 / 160 (1.88%)

0 / 6 (0.00%)

0 / 12 (0.00%)

3 / 172 (1.74%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

0 / 3

deaths causally related to treatment / all

0 / 0

Vomiting

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Biloma

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

1 / 5 (20.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Cholangitis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 2

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Cholestasis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Hepatic cirrhosis

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Hepatic haematoma

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

1 / 36 (2.78%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Hepatic pain

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

1 / 36 (2.78%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Hyperbilirubinaemia

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

2 / 26 (7.69%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Calculus urinary

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

2 / 36 (5.56%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Infections and infestations

Herpes zoster

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Lung infection

subjects affected / exposed

1 / 11 (9.09%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 1

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

1 / 26 (3.85%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

1 / 36 (2.78%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

1 / 1

0 / 0

1 / 2

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Pyelonephritis acute

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

1 / 30 (3.33%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Varicella

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

1 / 20 (5.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

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

Hypercalcaemia

subjects affected / exposed

0 / 11 (0.00%)

1 / 6 (16.67%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

1 / 160 (0.63%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

1 / 2

0 / 0

1 / 2

0 / 0

1 / 2

deaths causally related to treatment / all

0 / 0

Hyperglycaemia

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

0 / 26 (0.00%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

0 / 160 (0.00%)

0 / 6 (0.00%)

1 / 6 (16.67%)

1 / 12 (8.33%)

1 / 172 (0.58%)

occurrences causally related to treatment / all

0 / 0

1 / 1

deaths causally related to treatment / all

0 / 0

Hypoglycaemia

subjects affected / exposed

0 / 11 (0.00%)

0 / 6 (0.00%)

0 / 5 (0.00%)

2 / 26 (7.69%)

0 / 19 (0.00%)

0 / 7 (0.00%)

0 / 30 (0.00%)

0 / 36 (0.00%)

0 / 20 (0.00%)

2 / 160 (1.25%)

0 / 6 (0.00%)

0 / 12 (0.00%)

2 / 172 (1.16%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 2

0 / 0

0 / 2

deaths causally related to treatment / all

0 / 0

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	Phase I Part 50 mg Fasted	Phase I Part 80 mg Fasted	Phase I Part 80 mg Fed	Phase I Part 120 mg Fasted	Phase I Part 120 mg Fed	Phase I Part 150 mg Fasted	Phase II Part Group 1	Phase II Part Group 2	Phase II Part Group 3	All Patients Single agent	Phase I Part FGF401 80 mg + PDR001 300 mg	Phase I Part FGF401 120 mg + PDR001 300 mg	All Patients Combination	All Patients
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 11 (100.00%)	6 / 6 (100.00%)	5 / 5 (100.00%)	26 / 26 (100.00%)	19 / 19 (100.00%)	7 / 7 (100.00%)	30 / 30 (100.00%)	36 / 36 (100.00%)	20 / 20 (100.00%)	160 / 160 (100.00%)	6 / 6 (100.00%)	6 / 6 (100.00%)	12 / 12 (100.00%)	172 / 172 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Cancer pain
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Pyogenic granuloma
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Tumour associated fever
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	1
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Haematoma
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	0	2
Hot flush
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	0 / 160 (0.00%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 12 (16.67%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	2	2
Hypertension
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	2 / 7 (28.57%)	0 / 30 (0.00%)	3 / 36 (8.33%)	2 / 20 (10.00%)	9 / 160 (5.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	9 / 172 (5.23%)
occurrences all number	0	1	0	1	0	4	0	5	2	13	0	0	0	13
Hypotension
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Inferior vena cava syndrome
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Vascular compression
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Vena cava thrombosis
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Venous thrombosis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
General disorders and administration site conditions
Asthenia
subjects affected / exposed	2 / 11 (18.18%)	2 / 6 (33.33%)	0 / 5 (0.00%)	4 / 26 (15.38%)	3 / 19 (15.79%)	2 / 7 (28.57%)	3 / 30 (10.00%)	6 / 36 (16.67%)	4 / 20 (20.00%)	26 / 160 (16.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	26 / 172 (15.12%)
occurrences all number	3	3	0	5	4	2	4	14	8	43	0	0	0	43
Chest discomfort
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	2 / 30 (6.67%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	2	0	0	2	0	0	0	2
Chest pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Chills
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	3 / 30 (10.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	5 / 172 (2.91%)
occurrences all number	0	0	0	1	0	0	3	0	3	7	0	0	0	7
Face oedema
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Fatigue
subjects affected / exposed	2 / 11 (18.18%)	1 / 6 (16.67%)	0 / 5 (0.00%)	6 / 26 (23.08%)	4 / 19 (21.05%)	0 / 7 (0.00%)	2 / 30 (6.67%)	8 / 36 (22.22%)	7 / 20 (35.00%)	30 / 160 (18.75%)	1 / 6 (16.67%)	2 / 6 (33.33%)	3 / 12 (25.00%)	33 / 172 (19.19%)
occurrences all number	2	1	0	6	5	0	2	10	9	35	1	2	3	38
Gait disturbance
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
General physical health deterioration
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	0	2
Hernia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	1
Influenza like illness
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Injection site pruritus
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Localised oedema
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	0	0	1	0	2	0	0	0	2
Malaise
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	2	0	0	0	1	0	3	0	0	0	3
Mucosal inflammation
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Non-cardiac chest pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Oedema
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	3 / 172 (1.74%)
occurrences all number	0	0	0	1	0	0	0	1	0	2	1	0	1	3
Oedema peripheral
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	9 / 26 (34.62%)	0 / 19 (0.00%)	0 / 7 (0.00%)	8 / 30 (26.67%)	9 / 36 (25.00%)	3 / 20 (15.00%)	30 / 160 (18.75%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 12 (16.67%)	32 / 172 (18.60%)
occurrences all number	0	2	0	10	0	0	8	10	3	33	0	3	3	36
Pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	0 / 30 (0.00%)	2 / 36 (5.56%)	1 / 20 (5.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	0	0	0	0	0	1	0	2	1	4	0	0	0	4
Peripheral swelling
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	1 / 7 (14.29%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	1	1	1	0	0	3	0	0	0	3
Pyrexia
subjects affected / exposed	3 / 11 (27.27%)	0 / 6 (0.00%)	2 / 5 (40.00%)	6 / 26 (23.08%)	1 / 19 (5.26%)	1 / 7 (14.29%)	9 / 30 (30.00%)	4 / 36 (11.11%)	5 / 20 (25.00%)	31 / 160 (19.38%)	1 / 6 (16.67%)	3 / 6 (50.00%)	4 / 12 (33.33%)	35 / 172 (20.35%)
occurrences all number	6	0	2	8	1	1	13	5	12	48	1	3	4	52
Vessel puncture site bruise
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Female genital tract fistula
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Oedema genital
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Pelvic pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	1 / 20 (5.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	1	0	1	2	0	0	0	2
Scrotal oedema
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	1 / 7 (14.29%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	1	0	0	0	2	0	0	0	2
Varicocele
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Respiratory, thoracic and mediastinal disorders
Bronchostenosis
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Cough
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 26 (7.69%)	2 / 19 (10.53%)	2 / 7 (28.57%)	7 / 30 (23.33%)	3 / 36 (8.33%)	2 / 20 (10.00%)	19 / 160 (11.88%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	20 / 172 (11.63%)
occurrences all number	1	0	0	3	2	2	8	4	2	22	0	2	2	24
Dysphonia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	2 / 160 (1.25%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	0	0	0	1	1	2	1	0	1	3
Dyspnoea
subjects affected / exposed	1 / 11 (9.09%)	1 / 6 (16.67%)	1 / 5 (20.00%)	3 / 26 (11.54%)	0 / 19 (0.00%)	1 / 7 (14.29%)	4 / 30 (13.33%)	3 / 36 (8.33%)	3 / 20 (15.00%)	17 / 160 (10.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	17 / 172 (9.88%)
occurrences all number	1	1	1	3	0	1	5	3	4	19	0	0	0	19
Dyspnoea exertional
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	1	1	2
Epistaxis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	1 / 20 (5.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	0	0	1	0	1	2	0	1	1	3
Haemoptysis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	3 / 30 (10.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	5 / 172 (2.91%)
occurrences all number	0	0	1	0	0	1	3	0	0	5	0	0	0	5
Hiccups
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	0	1	0	0	2	0	0	0	2
Lung disorder
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Nasal congestion
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Oropharyngeal pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	2 / 30 (6.67%)	1 / 36 (2.78%)	0 / 20 (0.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	0	0	0	0	0	1	2	1	0	4	0	0	0	4
Orthopnoea
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Pleural effusion
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	2 / 20 (10.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	1	0	0	0	0	2	3	0	0	0	3
Pneumonitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	1	1	2
Productive cough
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	3 / 30 (10.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	6 / 160 (3.75%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	7 / 172 (4.07%)
occurrences all number	1	0	0	1	0	0	3	1	0	6	0	1	1	7
Pulmonary oedema
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Rhinorrhoea
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Sputum increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Wheezing
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	2 / 36 (5.56%)	1 / 20 (5.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	5 / 172 (2.91%)
occurrences all number	0	2	0	0	0	0	1	2	2	7	0	0	0	7
Bulimia nervosa
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Depression
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	1	0	0	1	0	2	0	0	0	2
Emotional disorder
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Insomnia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 26 (3.85%)	1 / 19 (5.26%)	2 / 7 (28.57%)	4 / 30 (13.33%)	2 / 36 (5.56%)	5 / 20 (25.00%)	16 / 160 (10.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	17 / 172 (9.88%)
occurrences all number	0	0	1	1	1	2	4	2	5	16	0	1	1	17
Nightmare
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Sleep disorder
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	0	2
Investigations
Activated partial thromboplastin time prolonged
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	1	0	0	0	0	0	0	0	1	2	0	0	0	2
Alanine aminotransferase increased
subjects affected / exposed	3 / 11 (27.27%)	3 / 6 (50.00%)	2 / 5 (40.00%)	14 / 26 (53.85%)	11 / 19 (57.89%)	7 / 7 (100.00%)	13 / 30 (43.33%)	11 / 36 (30.56%)	6 / 20 (30.00%)	70 / 160 (43.75%)	0 / 6 (0.00%)	4 / 6 (66.67%)	4 / 12 (33.33%)	74 / 172 (43.02%)
occurrences all number	3	6	5	19	13	11	16	12	8	93	0	4	4	97
Alpha 1 foetoprotein increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Amylase increased
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	2 / 36 (5.56%)	0 / 20 (0.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	0	1	0	0	0	0	1	2	0	4	0	0	0	4
Aspartate aminotransferase increased
subjects affected / exposed	4 / 11 (36.36%)	3 / 6 (50.00%)	2 / 5 (40.00%)	16 / 26 (61.54%)	14 / 19 (73.68%)	7 / 7 (100.00%)	14 / 30 (46.67%)	11 / 36 (30.56%)	5 / 20 (25.00%)	76 / 160 (47.50%)	1 / 6 (16.67%)	5 / 6 (83.33%)	6 / 12 (50.00%)	82 / 172 (47.67%)
occurrences all number	6	4	3	22	20	13	15	14	9	106	1	6	7	113
Bacterial test positive
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Bilirubin conjugated increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	0 / 160 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	1
Blood albumin decreased
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	2 / 172 (1.16%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	2	0	2	3
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 5 (20.00%)	4 / 26 (15.38%)	5 / 19 (26.32%)	1 / 7 (14.29%)	4 / 30 (13.33%)	2 / 36 (5.56%)	2 / 20 (10.00%)	20 / 160 (12.50%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	21 / 172 (12.21%)
occurrences all number	1	0	1	6	5	1	5	2	2	23	0	1	1	24
Blood bilirubin increased
subjects affected / exposed	4 / 11 (36.36%)	3 / 6 (50.00%)	1 / 5 (20.00%)	11 / 26 (42.31%)	2 / 19 (10.53%)	0 / 7 (0.00%)	6 / 30 (20.00%)	3 / 36 (8.33%)	1 / 20 (5.00%)	31 / 160 (19.38%)	1 / 6 (16.67%)	2 / 6 (33.33%)	3 / 12 (25.00%)	34 / 172 (19.77%)
occurrences all number	5	3	2	16	2	0	7	3	1	39	1	2	3	42
Blood cholesterol increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 26 (3.85%)	2 / 19 (10.53%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	6 / 172 (3.49%)
occurrences all number	0	4	0	1	2	0	0	1	0	8	0	1	1	9
Blood creatinine increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	5 / 172 (2.91%)
occurrences all number	0	0	1	2	0	0	0	3	0	6	0	1	1	7
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Blood phosphorus decreased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	0 / 160 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	2	2
Blood uric acid increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
C-reactive protein increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	2	0	0	0	1	0	3	0	0	0	3
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	1 / 36 (2.78%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	1	0	0	1	1	0	3	0	0	0	3
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	4 / 26 (15.38%)	2 / 19 (10.53%)	0 / 7 (0.00%)	4 / 30 (13.33%)	3 / 36 (8.33%)	3 / 20 (15.00%)	17 / 160 (10.63%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 12 (16.67%)	19 / 172 (11.05%)
occurrences all number	0	1	0	5	2	0	4	3	3	18	1	1	2	20
Haemoglobin decreased
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
International normalised ratio increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Lipase increased
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	4 / 30 (13.33%)	6 / 36 (16.67%)	1 / 20 (5.00%)	14 / 160 (8.75%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	14 / 172 (8.14%)
occurrences all number	0	1	2	2	0	0	5	6	1	17	0	0	0	17
Lymphocyte count decreased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	0	2
Neutrophil count decreased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	2 / 30 (6.67%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 12 (16.67%)	4 / 172 (2.33%)
occurrences all number	0	0	0	0	0	0	2	0	0	2	0	3	3	5
Platelet count decreased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	2 / 30 (6.67%)	2 / 36 (5.56%)	1 / 20 (5.00%)	6 / 160 (3.75%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	7 / 172 (4.07%)
occurrences all number	0	0	1	0	0	0	2	2	1	6	0	2	2	8
Prothrombin time prolonged
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Transaminases increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	1	0	0	1	1	3	0	0	0	3
Weight decreased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	2 / 19 (10.53%)	1 / 7 (14.29%)	0 / 30 (0.00%)	4 / 36 (11.11%)	4 / 20 (20.00%)	12 / 160 (7.50%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	13 / 172 (7.56%)
occurrences all number	0	0	0	1	2	1	0	4	4	12	0	1	1	13
Weight increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	0	0	1	0	2	0	0	0	2
White blood cell count increased
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Injury, poisoning and procedural complications
Animal bite
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Bone contusion
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Clavicle fracture
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Face injury
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Fall
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Fracture
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Humerus fracture
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Joint dislocation
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Ligament sprain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Periorbital haemorrhage
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Post procedural discharge
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Procedural pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	5 / 30 (16.67%)	0 / 36 (0.00%)	1 / 20 (5.00%)	7 / 160 (4.38%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	7 / 172 (4.07%)
occurrences all number	0	0	0	1	0	0	5	0	1	7	0	0	0	7
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Bradycardia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Cyanosis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Palpitations
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	2 / 172 (1.16%)
occurrences all number	0	0	1	0	0	0	0	0	0	1	1	0	1	2
Sinus tachycardia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Ventricular extrasystoles
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Nervous system disorders
Aphonia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Cervical radiculopathy
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Dizziness
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	2 / 30 (6.67%)	0 / 36 (0.00%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	1	0	2	0	0	3	0	0	0	3
Dysgeusia
subjects affected / exposed	3 / 11 (27.27%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	1 / 36 (2.78%)	1 / 20 (5.00%)	6 / 160 (3.75%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	7 / 172 (4.07%)
occurrences all number	3	0	0	0	0	0	1	1	1	6	0	1	1	7
Headache
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	4 / 30 (13.33%)	3 / 36 (8.33%)	3 / 20 (15.00%)	12 / 160 (7.50%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	13 / 172 (7.56%)
occurrences all number	1	0	1	0	0	0	4	3	3	12	0	1	1	13
Hemiparesis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Hypotonia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Memory impairment
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Neuropathy peripheral
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Paraesthesia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Paraparesis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Peripheral sensory neuropathy
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	0 / 160 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	1
Post herpetic neuralgia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Sciatica
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	1	1	2	0	0	0	2
Seizure
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Somnolence
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Spinal cord compression
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Taste disorder
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Visual field defect
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 26 (11.54%)	2 / 19 (10.53%)	1 / 7 (14.29%)	5 / 30 (16.67%)	1 / 36 (2.78%)	5 / 20 (25.00%)	18 / 160 (11.25%)	2 / 6 (33.33%)	2 / 6 (33.33%)	4 / 12 (33.33%)	22 / 172 (12.79%)
occurrences all number	1	0	0	5	2	1	5	1	5	20	2	2	4	24
Hyperglobulinaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	0	0	0	1
Iron deficiency anaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	2	0	0	2	0	0	0	2
Leukopenia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	1 / 19 (5.26%)	1 / 7 (14.29%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	1	1	1	0	0	0	3	0	0	0	3
Lymph node pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Lymphopenia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	2	0	0	0	0	0	2	0	0	0	2
Thrombocytopenia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	1	0	0	0	0	2	0	0	0	2
Ear and labyrinth disorders
Autophony
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Vertigo
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	0	0	1	0	2	0	0	0	2
Vestibular disorder
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Eye disorders
Eye swelling
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Gastrointestinal disorders
Abdominal discomfort
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	3 / 172 (1.74%)
occurrences all number	0	0	1	0	0	0	1	0	0	2	1	0	1	3
Abdominal distension
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 5 (20.00%)	3 / 26 (11.54%)	0 / 19 (0.00%)	3 / 7 (42.86%)	3 / 30 (10.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	13 / 160 (8.13%)	0 / 6 (0.00%)	3 / 6 (50.00%)	3 / 12 (25.00%)	16 / 172 (9.30%)
occurrences all number	1	0	1	4	0	3	3	1	1	14	0	4	4	18
Abdominal pain
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	3 / 5 (60.00%)	3 / 26 (11.54%)	4 / 19 (21.05%)	0 / 7 (0.00%)	5 / 30 (16.67%)	6 / 36 (16.67%)	9 / 20 (45.00%)	31 / 160 (19.38%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 12 (16.67%)	33 / 172 (19.19%)
occurrences all number	0	1	3	3	5	0	5	8	12	37	0	2	2	39
Abdominal pain lower
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Abdominal pain upper
subjects affected / exposed	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 5 (0.00%)	7 / 26 (26.92%)	1 / 19 (5.26%)	0 / 7 (0.00%)	5 / 30 (16.67%)	5 / 36 (13.89%)	1 / 20 (5.00%)	21 / 160 (13.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	21 / 172 (12.21%)
occurrences all number	1	1	0	8	1	0	6	8	1	26	0	0	0	26
Abdominal tenderness
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Aerophagia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Anal incontinence
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Angular cheilitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Ascites
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	2 / 5 (40.00%)	5 / 26 (19.23%)	0 / 19 (0.00%)	2 / 7 (28.57%)	4 / 30 (13.33%)	3 / 36 (8.33%)	2 / 20 (10.00%)	19 / 160 (11.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	19 / 172 (11.05%)
occurrences all number	0	2	2	5	0	2	4	3	2	20	0	0	0	20
Chronic gastritis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Colitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Constipation
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 5 (20.00%)	4 / 26 (15.38%)	1 / 19 (5.26%)	0 / 7 (0.00%)	5 / 30 (16.67%)	5 / 36 (13.89%)	6 / 20 (30.00%)	23 / 160 (14.38%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	24 / 172 (13.95%)
occurrences all number	1	0	1	4	1	0	5	6	8	26	1	0	1	27
Dental caries
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Diarrhoea
subjects affected / exposed	8 / 11 (72.73%)	4 / 6 (66.67%)	4 / 5 (80.00%)	18 / 26 (69.23%)	14 / 19 (73.68%)	7 / 7 (100.00%)	23 / 30 (76.67%)	23 / 36 (63.89%)	17 / 20 (85.00%)	118 / 160 (73.75%)	3 / 6 (50.00%)	4 / 6 (66.67%)	7 / 12 (58.33%)	125 / 172 (72.67%)
occurrences all number	16	5	8	25	19	8	42	44	35	202	5	6	11	213
Dry mouth
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	3 / 36 (8.33%)	1 / 20 (5.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	5 / 172 (2.91%)
occurrences all number	1	0	0	0	0	0	0	4	1	6	0	0	0	6
Duodenal obstruction
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Duodenal ulcer
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	1	0	0	1	0	0	1	0	0	3	0	0	0	3
Duodenitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Dyspepsia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	4 / 36 (11.11%)	0 / 20 (0.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	0	0	0	0	0	0	0	4	0	4	0	0	0	4
Dysphagia
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	2 / 36 (5.56%)	1 / 20 (5.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	5 / 172 (2.91%)
occurrences all number	1	0	0	0	0	0	1	2	1	5	0	0	0	5
Eructation
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Flatulence
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Gastric disorder
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Gastric ulcer
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Gastritis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	1	0	0	1	0	0	0	0	2	0	0	0	2
Gastrointestinal sounds abnormal
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	2	0	0	0	0	0	0	0	2	0	0	0	2
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	4 / 26 (15.38%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	6 / 160 (3.75%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	6 / 172 (3.49%)
occurrences all number	0	0	0	4	0	0	0	1	1	6	0	0	0	6
Haematemesis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	2	0	0	2	0	0	0	2
Haematochezia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Haemorrhoidal haemorrhage
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	2 / 20 (10.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	0	4	4	0	0	0	4
Haemorrhoids
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	1	0	1	0	2	0	0	0	2
Melaena
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	1 / 7 (14.29%)	2 / 30 (6.67%)	0 / 36 (0.00%)	0 / 20 (0.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	0	0	0	1	0	1	2	0	0	4	0	0	0	4
Nausea
subjects affected / exposed	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 5 (0.00%)	5 / 26 (19.23%)	6 / 19 (31.58%)	1 / 7 (14.29%)	7 / 30 (23.33%)	6 / 36 (16.67%)	11 / 20 (55.00%)	38 / 160 (23.75%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 12 (16.67%)	40 / 172 (23.26%)
occurrences all number	2	1	0	5	6	2	7	8	14	45	0	3	3	48
Oesophageal stenosis
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Oesophageal ulcer
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Oesophageal varices haemorrhage
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Oesophagitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	0	0	1	0	2	0	0	0	2
Proctalgia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Salivary hypersecretion
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Stomatitis
subjects affected / exposed	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	1 / 36 (2.78%)	0 / 20 (0.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	2	0	0	0	0	0	1	1	0	4	0	0	0	4
Toothache
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	1	0	0	0	0	2	0	0	0	2
Upper gastrointestinal haemorrhage
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Varices oesophageal
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Vomiting
subjects affected / exposed	1 / 11 (9.09%)	1 / 6 (16.67%)	1 / 5 (20.00%)	4 / 26 (15.38%)	6 / 19 (31.58%)	1 / 7 (14.29%)	5 / 30 (16.67%)	4 / 36 (11.11%)	9 / 20 (45.00%)	32 / 160 (20.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	33 / 172 (19.19%)
occurrences all number	1	1	1	4	8	1	9	8	11	44	0	1	1	45
Hepatobiliary disorders
Hepatic function abnormal
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Hepatic pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	1 / 20 (5.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	5 / 172 (2.91%)
occurrences all number	0	0	1	1	0	0	0	2	1	5	0	0	0	5
Hepatocellular injury
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	1	0	0	0	0	1	2	4	0	0	0	4
Hepatomegaly
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	2	0	0	0	0	0	2	0	0	0	2
Hepatorenal syndrome
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Hyperbilirubinaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	1	3	0	0	0	1	5	0	0	0	5
Jaundice
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	2 / 30 (6.67%)	1 / 36 (2.78%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	0	0	2	1	0	3	0	0	0	3
Jaundice cholestatic
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Portal vein thrombosis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	1	0	0	0	1	1	3	0	0	0	3
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Dry skin
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	4 / 36 (11.11%)	2 / 20 (10.00%)	7 / 160 (4.38%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	8 / 172 (4.65%)
occurrences all number	0	0	0	1	0	0	0	5	2	8	1	0	1	9
Ecchymosis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Night sweats
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	3 / 36 (8.33%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	0	0	0	3	0	3	0	0	0	3
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	1	1	0	2	0	0	0	2
Pruritus
subjects affected / exposed	2 / 11 (18.18%)	2 / 6 (33.33%)	1 / 5 (20.00%)	4 / 26 (15.38%)	5 / 19 (26.32%)	1 / 7 (14.29%)	5 / 30 (16.67%)	8 / 36 (22.22%)	0 / 20 (0.00%)	28 / 160 (17.50%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 12 (16.67%)	30 / 172 (17.44%)
occurrences all number	3	2	1	4	5	1	5	10	0	31	0	4	4	35
Rash
subjects affected / exposed	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	1 / 30 (3.33%)	0 / 36 (0.00%)	2 / 20 (10.00%)	6 / 160 (3.75%)	0 / 6 (0.00%)	2 / 6 (33.33%)	2 / 12 (16.67%)	8 / 172 (4.65%)
occurrences all number	1	1	0	0	0	1	1	0	2	6	0	4	4	10
Rash macular
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	0	1
Rash maculo-papular
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Rosacea
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Seborrhoeic dermatitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	0	2
Skin fissures
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	4	0	4	0	0	0	4
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Contracted bladder
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Haematuria
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	1	0	0	0	3	1	5	0	0	0	5
Leukocyturia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Neurogenic bladder
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Nocturia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Pollakiuria
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Proteinuria
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Urinary retention
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	0	1	0	0	2	0	0	0	2
Endocrine disorders
Cortisol deficiency
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Hyperthyroidism
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	0 / 160 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	1
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	1 / 20 (5.00%)	3 / 160 (1.88%)	1 / 6 (16.67%)	1 / 6 (16.67%)	2 / 12 (16.67%)	5 / 172 (2.91%)
occurrences all number	0	0	0	0	0	0	0	3	1	4	1	1	2	6
Back pain
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	1 / 7 (14.29%)	5 / 30 (16.67%)	4 / 36 (11.11%)	1 / 20 (5.00%)	14 / 160 (8.75%)	2 / 6 (33.33%)	0 / 6 (0.00%)	2 / 12 (16.67%)	16 / 172 (9.30%)
occurrences all number	0	1	0	2	0	1	5	4	1	14	2	0	2	16
Flank pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	2 / 30 (6.67%)	0 / 36 (0.00%)	0 / 20 (0.00%)	3 / 160 (1.88%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	4 / 172 (2.33%)
occurrences all number	0	0	0	0	1	0	2	0	0	3	2	0	2	5
Groin pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1
Muscle spasms
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	0	0	0	2	1	3	0	0	0	3
Muscular weakness
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	2	0	0	2	0	0	0	2
Musculoskeletal chest pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	1 / 30 (3.33%)	0 / 36 (0.00%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	0	1	1	0	1	3	0	0	0	3
Musculoskeletal pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 26 (11.54%)	1 / 19 (5.26%)	0 / 7 (0.00%)	3 / 30 (10.00%)	2 / 36 (5.56%)	3 / 20 (15.00%)	12 / 160 (7.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	12 / 172 (6.98%)
occurrences all number	0	0	0	3	1	0	3	3	3	13	0	0	0	13
Myalgia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	3 / 30 (10.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	5 / 172 (2.91%)
occurrences all number	0	0	0	0	0	0	3	0	1	4	0	1	1	5
Neck pain
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	1 / 20 (5.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	1	0	1	2	0	0	0	2
Osteoporosis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	0	2
Pain in extremity
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	2 / 30 (6.67%)	0 / 36 (0.00%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	1	0	0	0	0	2	0	0	3	0	0	0	3
Spinal pain
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	0	0	1
Tendonitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Infections and infestations
Anal abscess
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Bronchitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	1	0	0	1	1	3	0	0	0	3
Candida infection
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	0	0	1
Folliculitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	0 / 160 (0.00%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	1	1
Gastroenteritis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	2	0	2	0	0	0	2
Helicobacter infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Hepatitis B
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Herpes virus infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	1	0	0	0	1	2	0	0	0	2
Herpes zoster
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	1	1	0	2	0	0	0	2
Hordeolum
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Infected dermal cyst
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Lung infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	1	1	0	2	0	0	0	2
Nasopharyngitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	1 / 7 (14.29%)	1 / 30 (3.33%)	2 / 36 (5.56%)	0 / 20 (0.00%)	5 / 160 (3.13%)	2 / 6 (33.33%)	0 / 6 (0.00%)	2 / 12 (16.67%)	7 / 172 (4.07%)
occurrences all number	0	0	0	0	1	1	1	3	0	6	2	0	2	8
Oral candidiasis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Oral fungal infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Periodontitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Pneumonia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	2 / 30 (6.67%)	1 / 36 (2.78%)	0 / 20 (0.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	0	0	0	1	0	0	2	1	0	4	0	0	0	4
Rash pustular
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	2 / 172 (1.16%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	1	1	2
Rhinitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 26 (7.69%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	1 / 20 (5.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	5 / 172 (2.91%)
occurrences all number	0	0	0	2	1	0	0	1	1	5	0	0	0	5
Sinusitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	0 / 160 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	1
Skin infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	1
Staphylococcal infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	2	2	0	0	0	2
Tinea capitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	1
Tinea cruris
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	0 / 160 (0.00%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	1
Tinea versicolour
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Urinary tract infection
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	0	0	1	2	0	0	0	2	0	5	0	0	0	5
Vulvitis
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	3 / 11 (27.27%)	1 / 6 (16.67%)	0 / 5 (0.00%)	10 / 26 (38.46%)	2 / 19 (10.53%)	4 / 7 (57.14%)	6 / 30 (20.00%)	9 / 36 (25.00%)	12 / 20 (60.00%)	47 / 160 (29.38%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	47 / 172 (27.33%)
occurrences all number	3	1	0	10	2	4	6	10	12	48	0	0	0	48
Dyslipidaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1
Hypercalcaemia
subjects affected / exposed	1 / 11 (9.09%)	1 / 6 (16.67%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	1 / 20 (5.00%)	4 / 160 (2.50%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	4 / 172 (2.33%)
occurrences all number	1	3	0	3	0	0	0	0	1	8	0	0	0	8
Hyperglycaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 26 (3.85%)	1 / 19 (5.26%)	0 / 7 (0.00%)	1 / 30 (3.33%)	1 / 36 (2.78%)	0 / 20 (0.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	5 / 172 (2.91%)
occurrences all number	0	0	1	1	1	0	1	1	0	5	0	0	0	5
Hyperkalaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 5 (20.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	3	1	0	0	0	2	0	6	0	0	0	6
Hyperlipasaemia
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	2 / 36 (5.56%)	0 / 20 (0.00%)	6 / 160 (3.75%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	6 / 172 (3.49%)
occurrences all number	0	1	1	3	0	0	0	3	0	8	0	0	0	8
Hyperphosphataemia
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	1 / 7 (14.29%)	3 / 30 (10.00%)	1 / 36 (2.78%)	2 / 20 (10.00%)	8 / 160 (5.00%)	2 / 6 (33.33%)	3 / 6 (50.00%)	5 / 12 (41.67%)	13 / 172 (7.56%)
occurrences all number	0	1	0	0	0	1	5	1	2	10	2	4	6	16
Hypertriglyceridaemia
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	1	0	0	2	0	0	0	0	0	3	0	0	0	3
Hyperuricaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	2 / 26 (7.69%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	2	0	0	0	0	0	2	0	0	0	2
Hypoalbuminaemia
subjects affected / exposed	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 26 (11.54%)	0 / 19 (0.00%)	0 / 7 (0.00%)	7 / 30 (23.33%)	1 / 36 (2.78%)	2 / 20 (10.00%)	14 / 160 (8.75%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	14 / 172 (8.14%)
occurrences all number	1	0	0	3	0	0	8	1	3	16	0	0	0	16
Hypocalcaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	0	0	1
Hypokalaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	3 / 26 (11.54%)	0 / 19 (0.00%)	1 / 7 (14.29%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	5 / 160 (3.13%)	0 / 6 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	6 / 172 (3.49%)
occurrences all number	0	0	0	3	0	1	0	3	0	7	0	1	1	8
Hypomagnesaemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	2	0	0	0	0	2	0	0	0	2
Hyponatraemia
subjects affected / exposed	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 5 (20.00%)	3 / 26 (11.54%)	2 / 19 (10.53%)	0 / 7 (0.00%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	7 / 160 (4.38%)	1 / 6 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	8 / 172 (4.65%)
occurrences all number	0	1	2	3	2	0	0	0	0	8	1	0	1	9
Hypophosphataemia
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	1 / 19 (5.26%)	0 / 7 (0.00%)	1 / 30 (3.33%)	0 / 36 (0.00%)	1 / 20 (5.00%)	3 / 160 (1.88%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 172 (1.74%)
occurrences all number	0	0	0	0	1	0	1	0	1	3	0	0	0	3
Iron deficiency
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	0	0	1	0	2	0	0	0	2
Malnutrition
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	1 / 26 (3.85%)	0 / 19 (0.00%)	1 / 7 (14.29%)	0 / 30 (0.00%)	0 / 36 (0.00%)	0 / 20 (0.00%)	2 / 160 (1.25%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 172 (1.16%)
occurrences all number	0	0	0	1	0	1	0	0	0	2	0	0	0	2
Vitamin D deficiency
subjects affected / exposed	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 5 (0.00%)	0 / 26 (0.00%)	0 / 19 (0.00%)	0 / 7 (0.00%)	0 / 30 (0.00%)	1 / 36 (2.78%)	0 / 20 (0.00%)	1 / 160 (0.63%)	0 / 6 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 172 (0.58%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	1

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Were there any global substantial amendments to the protocol? Yes

13 Oct 2014

Issued 11 weeks before study start, the rationale for the amendment was to comply with health authority request to update the definition of Grade 3 diarrhea and Grade 3 hypercalcemia based on the NCI CTCAE.

18 Nov 2014

Issued 6 weeks before study start, the rationale for the amendment was to comply with the health authority suggestion to include the following: clarification of the starting dose planned for exploratory food effect cohort, clarification of the prophylactic treatment with anti-emetics in Cycle 1. For Japan only: specification of the informed consent procedure when subject was under the age of 20 years, specification of the additional ECG collection on Cycle 1 Day 1 for Japanese subjects only.

07 Jan 2015

Issued one week after study start, the purpose of this amendment was to add the amylase and lipase measurements to the local chemistry laboratory parameters collection plan in order to align with the criteria for dose-limiting toxicities specified in the protocol.

06 Dec 2016

Issued 101 weeks after study start, the primary purpose of this amendment was to add a combination treatment of FGF401 and PDR001, a humanized anti-programmed death-1 (PD-1) IgG4 antibody, in subjects with advanced hepatocellular carcinoma. In addition, the FGFR4/KLB/FGF19 molecular screening selection requirement for HCC subjects in the Phase II part of the FGF401 single agent was removed.

27 Sep 2018

Issued 195 weeks after study start, the main purposes of this amendment were: to incorporate health authority-requested language requiring study treatment discontinuation in the event of Stevens-Johnson syndrome (SJS)/ toxic epidermal necrolysis (TEN) (already implemented as part of an urgent safety measure released on 15-Jun-2018 due to an event in another study with PDR001 that did not involve FGF401) and to reduce study visits and assessments to ease the burden on patients who have been on study for more than 7 cycles, while maintaining access to study treatment and monitoring safety.

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 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Incidence rate of Dose-limiting Toxicity (DLT): Phase I only

Primary: Incidence rate of Dose-limiting Toxicity (DLT): Phase I only

Primary: Time to progression (TTP): Group 1 & Group 2 (Phase II only)

Primary: Time to progression (TTP): Group 1 & Group 2 (Phase II only)

Primary: Overall response rate (ORR) based on local assessment: Group 3 (Phase II only)

Primary: Overall response rate (ORR) based on local assessment: Group 3 (Phase II only)

Secondary: Best Overall Response (BOR) by Investigator assessment: Phase I and Phase II

Secondary: Best Overall Response (BOR) by Investigator assessment: Phase I and Phase II

Secondary: Overall Response Rate (ORR) by Investigator assessment Phase I and FGF401 single agent Phase II Groups 1 & 2

Secondary: Overall Response Rate (ORR) by Investigator assessment Phase I and FGF401 single agent Phase II Groups 1 & 2

Secondary: Disease Control Rate (DCR) by local Investigator assessment Phase I and FGF401 single agent Phase II Groups 1, 2 & 3

Secondary: Disease Control Rate (DCR) by local Investigator assessment Phase I and FGF401 single agent Phase II Groups 1, 2 & 3

Secondary: Time to Progression (TTP) - Phase I (single agent FGF401 & in combination with PDR001) dosed at RP2D

Secondary: Time to Progression (TTP) - Phase I (single agent FGF401 & in combination with PDR001) dosed at RP2D

Secondary: Overall Survival (OS) - Phase I (single agent & combination) dosed at RP2D and Phase II FGF401 single agent

Secondary: Overall Survival (OS) - Phase I (single agent & combination) dosed at RP2D and Phase II FGF401 single agent

Secondary: Progression-free Survival (PFS) - FGF401 single agent Phase II: Group 3

Secondary: Progression-free Survival (PFS) - FGF401 single agent Phase II: Group 3

Secondary: Presence and/or concentration of anti-PDR001 antibodies

Secondary: Presence and/or concentration of anti-PDR001 antibodies

Secondary: Cmax of PDR001 in combination with FGF401: Phase I

Secondary: Cmax of PDR001 in combination with FGF401: Phase I

Secondary: AUClast and AUCtau of PDR001 in combination with FGF401: Phase I

Secondary: AUClast and AUCtau of PDR001 in combination with FGF401: Phase I

Secondary: T1/2 of PDR001: Phase I

Secondary: T1/2 of PDR001: Phase I

Secondary: Cmax of FGF401: Phase I

Secondary: Cmax of FGF401: Phase I

Secondary: Cmax of FGF401 in combination with PDR001: Phase I

Secondary: Cmax of FGF401 in combination with PDR001: Phase I

Secondary: AUCinf, AUClast & AUCtau of FGF401: Phase I

Secondary: AUCinf, AUClast & AUCtau of FGF401: Phase I

Secondary: AUCinf, AUClast & AUCtau of FGF401 in combination with PDR001: Phase I

Secondary: AUCinf, AUClast & AUCtau of FGF401 in combination with PDR001: Phase I

Secondary: T1/2 of FGF401: Phase I

Secondary: T1/2 of FGF401: Phase I

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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