Trial Outcomes & Findings for Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer (NCT NCT02323126)

NCT ID: NCT02323126

Last Updated: 2022-02-28

Results Overview

PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PFS was modeled using a Weibull distribution and the PFS rate at 6 months was estimated from the posterior distribution.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

64 participants

Primary outcome timeframe

6 months

Results posted on

2022-02-28

Participant Flow

Participants took part in 13 investigative sites in 8 countries.

All patients were required to sign the molecular pre-screening consent to allow for the collection and submission of tumor tissue for determination and/or confirmation of protocol specific pre-requisite genetic alterations. After the molecular pre-screening, the screening period began once patients had signed the study informed consent. Screening evaluations were performed within 28 days prior to the first dose of study medication. After screening, the treatment period started on Cycle 1 Day 1.

Participant milestones

Participant milestones
Measure	Nivolumab and EGF816 Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Overall Study STARTED	18	16	30
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	18	16	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Nivolumab and EGF816 Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Overall Study Patient / guardian decision	0	1	2
Overall Study Progressive disease	14	8	14
Overall Study Physician Decision	0	1	3
Overall Study Death	1	1	4
Overall Study Adverse Event	3	5	7

Baseline Characteristics

Study of Efficacy and Safety of Nivolumab in Combination With EGF816 and of Nivolumab in Combination With INC280 in Patients With Previously Treated Non-small Cell Lung Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W	Total n=64 Participants Total of all reporting groups
Age, Continuous	62.6 years STANDARD_DEVIATION 8.77 • n=5 Participants	63.8 years STANDARD_DEVIATION 13.05 • n=7 Participants	64.9 years STANDARD_DEVIATION 8.45 • n=5 Participants	64.0 years STANDARD_DEVIATION 9.75 • n=4 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants	35 Participants n=4 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	8 Participants n=7 Participants	15 Participants n=5 Participants	29 Participants n=4 Participants
Race/Ethnicity, Customized Asian	4 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Race/Ethnicity, Customized Caucasian	14 Participants n=5 Participants	14 Participants n=7 Participants	26 Participants n=5 Participants	54 Participants n=4 Participants
Race/Ethnicity, Customized Other	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Unknown	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants

PRIMARY outcome

Timeframe: 6 months

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab.

PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). PFS was modeled using a Weibull distribution and the PFS rate at 6 months was estimated from the posterior distribution.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Progression-Free Survival (PFS) Rate at 6 Months Per RECIST v1.1	63.4 percentage of participants Interval 45.7 to 79.2	68.9 percentage of participants Interval 48.5 to 85.7	50.9 percentage of participants Interval 35.6 to 66.4

SECONDARY outcome

Timeframe: From start of treatment until end of treatment, assessed up to 4.7 years

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab.

Tumor response was based on local investigator assessment as per RECIST v1.1. ORR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR) or Partial Response (PR). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameter of all target lesions, taking as reference the baseline sum of diameters.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Overall Response Rate (ORR) Per RECIST v1.1	7 Participants	4 Participants	5 Participants

SECONDARY outcome

Timeframe: From start of treatment until end of treatment, assessed up to 4.7 years

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab.

Tumor response was based on local investigator assessment as per RECIST v1.1. DCR per RECIST 1.1 is defined as the percentage of participants with a best overall response of Complete Response (CR), Partial Response (PR) or Stable Disease (SD). For RECIST v1.1, CR=Disappearance of all non-nodal target lesions. In addition, any pathological lymph nodes assigned as target lesions must have a reduction in short axis to \< 10 mm; PR= At least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters; SD= Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for progression.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Disease Control Rate (DCR) Per RECIST v1.1	17 Participants	13 Participants	13 Participants

SECONDARY outcome

Timeframe: From start of treatment to first documented progression or death, assessed up to 5 years

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab.

PFS is the time from the 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. The median PFS was estimated using the Kaplan-Meier method. Tumor response was based on local investigator assessment as per RECIST v1.1

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Median Progression-Free Survival (PFS) Per RECIST v1.1	7.4 months Interval 3.7 to 11.1	6.2 months Interval 3.5 to 19.2	4.2 months Interval 1.8 to 7.4

SECONDARY outcome

Timeframe: 3 months

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab.

PFS rate represents the percentage of participants without a first documented progression or death due to any cause after the start of study treatment. Tumor response was based on local investigator assessment as per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). The PFS rate at 3 months was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Progression-Free Survival (PFS) Rate at 3 Months Per RECIST v1.1	83.3 percentage of participants Interval 56.8 to 94.3	86.7 percentage of participants Interval 56.4 to 96.5	53.8 percentage of participants Interval 33.3 to 70.6

SECONDARY outcome

Timeframe: 1 year

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab.

OS represents the percentage of participants who are alive after the start of study treatment. OS at 1 year was estimated using the Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Overall Survival (OS) at 1 Year	55.6 percentage of participants Interval 30.5 to 74.8	72.3 percentage of participants Interval 41.5 to 88.7	32.5 percentage of participants Interval 15.8 to 50.5

SECONDARY outcome

Timeframe: From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment.

Number of participants with AEs and SAEs, including changes from baseline in vital signs, electrocardiograms and laboratory results qualifying and reported as AEs. AE grades were based on the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Fatal SAEs	4 Participants	1 Participants	4 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs	18 Participants	16 Participants	30 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment-related AEs	17 Participants	16 Participants	27 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs with grade 3/4	18 Participants	14 Participants	24 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment-related AEs with grade 3/4	13 Participants	12 Participants	16 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) SAEs	14 Participants	8 Participants	18 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment-related SAEs	6 Participants	4 Participants	7 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment related fatal SAEs	2 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs leading to discontinuation	5 Participants	7 Participants	11 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Treatment-related AEs leading to discontinuation	5 Participants	7 Participants	9 Participants
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) AEs leading to dose adjustment/interruption	15 Participants	14 Participants	23 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment.

Number of participants with at least one dose reduction of EGF816, INC280 or nivolumab and number of participants with at least one dose interruption of EGF816, INC280 or nivolumab. Dose reduction was not allowed for nivolumab in this study.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab EGF816, dose reduction	5 Participants	—	—
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab EGF816, dose interruption	14 Participants	—	—
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab INC280, dose reduction	—	7 Participants	10 Participants
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab INC280, dose interruption	—	14 Participants	25 Participants
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab Nivolumab, dose reduction	0 Participants	0 Participants	0 Participants
Number of Participants With Dose Reductions and Dose Interruptions of EGF816, INC280 and Nivolumab Nivolumab, dose interruption	12 Participants	10 Participants	15 Participants

SECONDARY outcome

Timeframe: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment.

Dose intensity (mg/day) of EGF816 and INC280 was calculated as actual cumulative dose in milligrams divided by duration of exposure in days.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Dose Intensity of EGF816 and INC280 EGF816	141.5 mg/day Interval 81.0 to 150.0	—	—
Dose Intensity of EGF816 and INC280 INC280	—	609.4 mg/day Interval 254.0 to 800.0	636.7 mg/day Interval 240.0 to 800.0

SECONDARY outcome

Timeframe: From first dose of study treatment until last dose of study treatment, up to maximum 4.7 years

Population: All patients who had received at least 1 dose of INC280, EGF816 or nivolumab and had at least 1 valid post-baseline safety assessment.

Dose intensity (mg/kg biweekly) of nivolumab was calculated as actual cumulative dose in mg/kg divided by duration of exposure in days and then multiplied by 14 days (2 weeks).

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Dose Intensity of Nivolumab	3.0 mg/kg/2-week Interval 3.0 to 3.0	3.0 mg/kg/2-week Interval 3.0 to 3.0	3.0 mg/kg/2-week Interval 3.0 to 3.0

SECONDARY outcome

Timeframe: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.

Population: All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast).

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=11 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Maximum Observed Plasma Concentration (Cmax) of EGF816	935 ng/mL Geometric Coefficient of Variation 40.8	—	—

SECONDARY outcome

Timeframe: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.

Population: All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast).

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=11 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Time to Reach Maximum Plasma Concentration (Tmax) of EGF816	3.00 hours Interval 1.0 to 6.0	—	—

SECONDARY outcome

Timeframe: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.

Population: All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast).

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=11 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of EGF816	5560 hr*ng/mL Geometric Coefficient of Variation 42.8	—	—

SECONDARY outcome

Timeframe: pre-dose, 1, 3, 6 and 8 hours post EGF816 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.

Population: All patients who had extensive PK sampling and provided an EGF816 evaluable PK profile on Cycle 1 Day 15. The EGF816 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast).

Pharmacokinetic (PK) parameters were calculated based on EGF816 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=11 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Minimum Observed Plasma Concentration (Cmin) of EGF816	398 ng/mL Geometric Coefficient of Variation 48.8	—	—

SECONDARY outcome

Timeframe: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.

Population: All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile.

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmax is defined as the maximum (peak) observed plasma concentration following a dose.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=5 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Maximum Observed Plasma Concentration (Cmax) of INC280	6190 ng/mL Geometric Coefficient of Variation 83.9	—	—

SECONDARY outcome

Timeframe: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.

Population: All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile.

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Tmax is defined as the time to reach maximum (peak) plasma concentration following a dose. Actual recorded sampling times were considered for the calculations.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=5 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Time to Reach Maximum Plasma Concentration (Tmax) of INC280	0.983 hours Interval 0.667 to 1.08	—	—

SECONDARY outcome

Timeframe: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.

Population: All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile.

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. The linear trapezoidal method was used for AUClast calculation.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=5 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Area Under the Plasma Concentration-time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUClast) of INC280	19300 hr*ng/mL Geometric Coefficient of Variation 97.5	—	—

SECONDARY outcome

Timeframe: pre-dose, 1, 3, 6 and 8 hours post INC280 dose on Cycle 1 Day 15. The duration of one cycle was 28 days.

Population: All patients who had extensive PK sampling and provided an INC280 evaluable PK profile on Cycle 1 Day 15. The INC280 PK profile was considered evaluable if all the following conditions were satisfied: patient had received planned doses and patient had provided at least 1 valid primary PK parameter (Cmax, Tmax, AUClast). In the Group 2B, no patients provided an INC280 evaluable PK profile.

Pharmacokinetic (PK) parameters were calculated based on INC280 plasma concentrations by using non-compartmental methods. Cmin is defined as the minimum observed plasma concentration following a dose.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=5 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Minimum Observed Plasma Concentration (Cmin) of INC280	428 ng/mL Geometric Coefficient of Variation 105	—	—

SECONDARY outcome

Timeframe: pre-dose on Cycle 1 Day 1 (groups 2A and 2B only) and pre-dose on Cycle 1 Day 15 and Cycle 2 Day 1 (all groups). The duration of one cycle was 28 days.

Population: All patients who had provided at least 1 evaluable nivolumab PK concentration. For a nivolumab PK concentration to be evaluable in pre-dose samples, a patient was required to have the sample collected before the next dose administration. Samples were not collected in Group 1 on Cycle 1 Day 1.

Nivolumab serum concentrations were assessed in samples taken at pre-dose. Pre-dose samples were collected before the next dose administration.

Outcome measures

Outcome measures
Measure	Nivolumab and EGF816 n=18 Participants Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=15 Participants Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=29 Participants Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W
Pre-dose Serum Concentration of Nivolumab Cycle 1 Day 1	—	NA ng/mL Geometric Coefficient of Variation NA Concentrations below the limit of quantification (\<0.20 ng/mL)	NA ng/mL Geometric Coefficient of Variation NA Concentrations below the limit of quantification (\<0.20 ng/mL)
Pre-dose Serum Concentration of Nivolumab Cycle 1 Day 15	17.2 ng/mL Geometric Coefficient of Variation 28.6	18.6 ng/mL Geometric Coefficient of Variation 45.3	19.5 ng/mL Geometric Coefficient of Variation 35.6
Pre-dose Serum Concentration of Nivolumab Cycle 2 Day 1	21.3 ng/mL Geometric Coefficient of Variation 54.6	35.7 ng/mL Geometric Coefficient of Variation 26.6	26.4 ng/mL Geometric Coefficient of Variation 77.1

Adverse Events

Nivolumab and EGF816

Serious events: 14 serious events

Other events: 18 other events

Deaths: 8 deaths

Nivolumab and INC280, High cMet

Serious events: 8 serious events

Other events: 16 other events

Deaths: 4 deaths

Nivolumab and INC280, Low cMet

Serious events: 18 serious events

Other events: 29 other events

Deaths: 10 deaths

Nivolumab and INC280, High+Low cMet

Serious events: 26 serious events

Other events: 45 other events

Deaths: 14 deaths

Serious adverse events

Serious adverse events
Measure	Nivolumab and EGF816 n=18 participants at risk Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 participants at risk Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 participants at risk Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High+Low cMet n=46 participants at risk Group 2A+2B (low and high cMet): INC280 400 mg BID + Nivolumab 3 mg/kg Q2W
Blood and lymphatic system disorders Disseminated intravascular coagulation	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Blood and lymphatic system disorders Neutropenia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Cardiac disorders Acute myocardial infarction	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Cardiac disorders Angina pectoris	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Cardiac disorders Myocardial infarction	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Cardiac disorders Sinus tachycardia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Endocrine disorders Adrenal insufficiency	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Eye disorders Diplopia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Abdominal pain	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Colitis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Diarrhoea	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Pancreatitis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Vomiting	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Condition aggravated	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Fatigue	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Gait disturbance	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders General physical health deterioration	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Pyrexia	22.2% 4/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.0% 3/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	8.7% 4/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Hepatobiliary disorders Hepatic function abnormal	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Immune system disorders Anaphylactic reaction	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Immune system disorders Contrast media allergy	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Abdominal wall abscess	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Bacterial infection	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Bronchitis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Pneumonia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Respiratory tract infection	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Upper respiratory tract infection	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Urinary tract infection	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Blood creatinine increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Diabetic ketoacidosis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hyperamylasaemia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Back pain	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Bone pain	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Myositis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Ataxia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Cerebral ischaemia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Cerebrovascular accident	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Dysaesthesia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Dysarthria	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Headache	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Hemiparesis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Ischaemic stroke	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Lethargy	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Somnolence	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Syncope	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Psychiatric disorders Confusional state	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	8.7% 4/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Interstitial lung disease	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Pleural effusion	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Pneumonitis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Pneumothorax	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Respiratory failure	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Tachypnoea	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Rash macular	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Rash maculo-papular	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Stevens-Johnson syndrome	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Vascular disorders Giant cell arteritis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.

Other adverse events

Other adverse events
Measure	Nivolumab and EGF816 n=18 participants at risk Group 1: EGF816 150 mg QD + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High cMet n=16 participants at risk Group 2A: INC280 400 mg BID, High cMET + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, Low cMet n=30 participants at risk Group 2B: INC280 400 mg BID, Low cMet + Nivolumab 3 mg/kg Q2W	Nivolumab and INC280, High+Low cMet n=46 participants at risk Group 2A+2B (low and high cMet): INC280 400 mg BID + Nivolumab 3 mg/kg Q2W
Nervous system disorders Headache	22.2% 4/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	31.2% 5/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.9% 5/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Hydrocephalus	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Lethargy	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Nervous system disorder	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Paraesthesia	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Peripheral sensory neuropathy	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Presyncope	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Sciatica	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Seizure	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Somnolence	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Speech disorder	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Spinal cord compression	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Tremor	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Product Issues Device occlusion	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Product Issues Thrombosis in device	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Psychiatric disorders Anxiety	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Dysaesthesia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Dysgeusia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Essential tremor	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Blood and lymphatic system disorders Anaemia	22.2% 4/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	25.0% 4/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	23.3% 7/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	23.9% 11/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Blood and lymphatic system disorders Leukopenia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Blood and lymphatic system disorders Neutropenia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Blood and lymphatic system disorders Thrombocytopenia	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Cardiac disorders Extrasystoles	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Cardiac disorders Tachycardia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Ear and labyrinth disorders Deafness	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Ear and labyrinth disorders Tinnitus	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Endocrine disorders Hyperthyroidism	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Endocrine disorders Hypophysitis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Endocrine disorders Hypothyroidism	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Eye disorders Dry eye	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Eye disorders Uveitis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Eye disorders Vision blurred	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Abdominal pain	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Abdominal pain upper	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.0% 3/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	8.7% 4/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Anal haemorrhage	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Aphthous ulcer	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Ascites	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Constipation	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	31.2% 5/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	15.2% 7/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Diarrhoea	50.0% 9/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	31.2% 5/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	20.0% 6/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	23.9% 11/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Dry mouth	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Dysphagia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Faeces discoloured	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Nausea	27.8% 5/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	81.2% 13/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	40.0% 12/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	54.3% 25/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Oesophageal pain	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Stomatitis	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Toothache	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Gastrointestinal disorders Vomiting	27.8% 5/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	56.2% 9/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	23.3% 7/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	34.8% 16/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Asthenia	38.9% 7/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	37.5% 6/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	33.3% 10/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	34.8% 16/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Catheter site swelling	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Chest discomfort	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Chills	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Face oedema	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Fatigue	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	31.2% 5/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.3% 4/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	19.6% 9/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Gait disturbance	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Influenza like illness	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Non-cardiac chest pain	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Oedema	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Oedema peripheral	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	50.0% 8/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	26.7% 8/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	34.8% 16/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Pain	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Peripheral swelling	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
General disorders Pyrexia	55.6% 10/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	37.5% 6/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.0% 3/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	19.6% 9/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Hepatobiliary disorders Cholecystitis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Hepatobiliary disorders Hepatic pain	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Abdominal wall abscess	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Bronchitis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Candida infection	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Cellulitis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Conjunctivitis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Cystitis bacterial	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Dermatitis infected	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Herpes simplex	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Herpes zoster	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Influenza	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Lower respiratory tract infection	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Nasopharyngitis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Oesophageal candidiasis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Oral candidiasis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Paronychia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Pneumonia	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Pulpitis dental	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Respiratory tract infection viral	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Sinusitis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Upper respiratory tract infection	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Infections and infestations Urinary tract infection	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Injury, poisoning and procedural complications Femur fracture	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Injury, poisoning and procedural complications Limb injury	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Injury, poisoning and procedural complications Lumbar vertebral fracture	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Injury, poisoning and procedural complications Muscle injury	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Injury, poisoning and procedural complications Procedural pain	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Alanine aminotransferase increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	16.7% 5/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	15.2% 7/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Amylase increased	33.3% 6/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	56.2% 9/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	20.0% 6/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	32.6% 15/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Aspartate aminotransferase increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	16.7% 5/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.0% 6/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Bilirubin conjugated increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Blood albumin decreased	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Blood alkaline phosphatase increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Blood bilirubin increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Blood creatine phosphokinase increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	20.0% 6/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.0% 6/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Blood creatinine increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	37.5% 6/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	30.0% 9/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	32.6% 15/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Blood glucose increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Blood triglycerides increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations C-reactive protein increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Gamma-glutamyltransferase increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	18.8% 3/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Lipase increased	22.2% 4/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	43.8% 7/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	20.0% 6/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	28.3% 13/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Lymphocyte count decreased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Platelet count decreased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Transaminases increased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations Weight decreased	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	8.7% 4/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Investigations White blood cell count decreased	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Cell death	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Decreased appetite	33.3% 6/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	30.0% 9/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	23.9% 11/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hypercalcaemia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hyperuricaemia	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hypoalbuminaemia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	30.0% 9/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	23.9% 11/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hypocalcaemia	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hypochloraemia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hypokalaemia	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	23.3% 7/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	19.6% 9/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hypomagnesaemia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.0% 3/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.9% 5/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hyponatraemia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hypophosphataemia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Metabolism and nutrition disorders Hypoproteinaemia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Arthralgia	22.2% 4/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	31.2% 5/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.3% 4/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	19.6% 9/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Back pain	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	18.8% 3/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.0% 3/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.0% 6/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Bone pain	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Muscle contracture	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Muscle spasms	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Muscular weakness	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Musculoskeletal stiffness	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	18.8% 3/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.0% 3/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.0% 6/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Pain in extremity	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.0% 3/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	8.7% 4/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Musculoskeletal and connective tissue disorders Spinal pain	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Infected naevus	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to meninges	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Balance disorder	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Cerebral ischaemia	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Nervous system disorders Dizziness	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	10.0% 3/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	8.7% 4/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Psychiatric disorders Insomnia	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.5% 3/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Psychiatric disorders Suicidal ideation	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Renal and urinary disorders Dysuria	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Renal and urinary disorders Pollakiuria	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Renal and urinary disorders Renal failure	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Renal and urinary disorders Renal impairment	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Renal and urinary disorders Urinary incontinence	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Reproductive system and breast disorders Breast haematoma	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Reproductive system and breast disorders Cystocele	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Reproductive system and breast disorders Genital ulceration	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Reproductive system and breast disorders Pelvic pain	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Reproductive system and breast disorders Perineal fistula	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Reproductive system and breast disorders Vulvovaginal discomfort	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Reproductive system and breast disorders Vulvovaginal pruritus	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Cough	22.2% 4/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	18.8% 3/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.3% 4/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	15.2% 7/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Dysphonia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea	22.2% 4/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	23.3% 7/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	19.6% 9/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Haemoptysis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Nasal dryness	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	8.7% 4/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Pneumonitis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	4.3% 2/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Respiratory, thoracic and mediastinal disorders Sleep apnoea syndrome	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Actinic keratosis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Alopecia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Dermatitis acneiform	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Dermatitis exfoliative	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Dry skin	22.2% 4/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.7% 2/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	8.7% 4/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Ecchymosis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Erythema	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Hyperhidrosis	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Lichenoid keratosis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Nail disorder	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Nail dystrophy	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Onychoclasis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Pain of skin	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Palmar erythema	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Pruritus	33.3% 6/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	12.5% 2/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.3% 4/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.0% 6/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Rash	66.7% 12/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	18.8% 3/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	13.3% 4/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	15.2% 7/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Rash erythematous	11.1% 2/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Rash maculo-papular	16.7% 3/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Rash pruritic	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Skin exfoliation	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Skin fissures	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Skin and subcutaneous tissue disorders Urticaria	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Vascular disorders Giant cell arteritis	0.00% 0/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	6.2% 1/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Vascular disorders Haematoma	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Vascular disorders Hypertension	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	3.3% 1/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	2.2% 1/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.
Vascular disorders Peripheral ischaemia	5.6% 1/18 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/16 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/30 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.	0.00% 0/46 • From first dose of study medication up to 100 days after last dose of study medication, with a maximum duration of 5 years. Any sign or symptom that occurs during the study treatment plus 100 days after last dose.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 862-778-8300

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
Publication restrictions are in place

Restriction type: OTHER