Trial Outcomes & Findings for An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820 to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors (NCT NCT01773421)

NCT ID: NCT01773421

Last Updated: 2023-06-22

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

45 participants

Primary outcome timeframe

Day 1 or 8: 0.5-48 hours

Results posted on

2023-06-22

Participant Flow

Participants took part in the study at 6 investigative sites in the Netherlands and United Kingdom from 30 June 2011 to 12 November 2017.

In Part A, a total of 18 participants were enrolled, out of which 15 participants were randomized and treated. In Part B, a total of 27 participants were enrolled, out of which 26 participants were treated.

Participant milestones

Participant milestones
Measure	Treatment Phase Part A: E7820 50 mg Fed+ E7820 50 mg Fasted Participants received E7820 50 milligram (mg), tablet, orally, under fed condition on Day 1, followed by E7820 50 mg, tablet, orally, under fasted condition on Day 8. A washout period of 7 days was maintained between the doses.	Treatment Phase Part A: E7820 50 mg Fasted + E7820 50 mg Fed Participants received E7820 50 mg, tablet, orally, under fasted condition on Day 1, followed by E7820 50 mg, tablet, orally, under fed condition on Day 8. A washout period of 7 days was maintained between the doses.	Treatment Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation.	Treatment Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation.	Extension Phase Part A: E7820 100 mg Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Extension Phase Part B: E7820 50 mg Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Treatment Phase STARTED	7	8	19	7	0	0
Treatment Phase COMPLETED	7	8	13	5	0	0
Treatment Phase NOT COMPLETED	0	0	6	2	0	0
Extension Phase STARTED	0	0	0	0	15	3
Extension Phase COMPLETED	0	0	0	0	12	1
Extension Phase NOT COMPLETED	0	0	0	0	3	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation.	Treatment Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation.	Extension Phase Part A: E7820 100 mg Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Extension Phase Part B: E7820 50 mg Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Treatment Phase Other	2	0	0	0
Treatment Phase Adverse Event	3	1	0	0
Treatment Phase Withdrawal by Subject	1	1	0	0
Extension Phase Other	0	0	1	2
Extension Phase Adverse Event	0	0	2	0

Baseline Characteristics

An Open-label, Dose Escalation, Pharmacodynamic, Pharmacokinetic, and Effect of Food Phase 1 Study of E7820 to Determine the Maximum Tolerated Dose Following Twice Daily Oral Administration in Subjects With Unresectable Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment Phase Part A: E7820 50 mg Fed+ E7820 50 mg Fasted n=7 Participants Participants received E7820 50 mg, tablet, orally, under fed condition on Day 1, followed by E7820 50 mg, tablet, orally, under fasted condition on Day 8. A washout period of 7 days was maintained between the doses.	Treatment Phase Part A: E7820 50 mg Fasted + E7820 50 mg Fed n=8 Participants Participants received E7820 50 mg, tablet, orally, under fasted condition on Day 1, followed by E7820 50 mg, tablet, orally, under fed condition on Day 8. A washout period of 7 days was maintained between the doses.	Treatment Phase Part B: E7820 50 mg n=19 Participants Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation.	Treatment Phase Part B: E7820 60 mg n=7 Participants Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation.	Total n=41 Participants Total of all reporting groups
Age, Customized Between 18 and 44 years	0 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants	4 Participants n=36 Participants
Age, Customized Between 45 and 64 years	5 Participants n=93 Participants	1 Participants n=4 Participants	8 Participants n=27 Participants	5 Participants n=483 Participants	19 Participants n=36 Participants
Age, Customized Between 65 and 74 years	1 Participants n=93 Participants	3 Participants n=4 Participants	9 Participants n=27 Participants	1 Participants n=483 Participants	14 Participants n=36 Participants
Age, Customized Greater than (>) 74 years	1 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	0 Participants n=483 Participants	4 Participants n=36 Participants
Sex: Female, Male Female	4 Participants n=93 Participants	3 Participants n=4 Participants	6 Participants n=27 Participants	2 Participants n=483 Participants	15 Participants n=36 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	5 Participants n=4 Participants	13 Participants n=27 Participants	5 Participants n=483 Participants	26 Participants n=36 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	7 Participants n=93 Participants	8 Participants n=4 Participants	19 Participants n=27 Participants	7 Participants n=483 Participants	41 Participants n=36 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race/Ethnicity, Customized White	6 Participants n=93 Participants	8 Participants n=4 Participants	19 Participants n=27 Participants	7 Participants n=483 Participants	40 Participants n=36 Participants
Race/Ethnicity, Customized Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race/Ethnicity, Customized Chinese	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	1 Participants n=36 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
ECOG Score 0	1 Participants n=93 Participants	4 Participants n=4 Participants	7 Participants n=27 Participants	1 Participants n=483 Participants	13 Participants n=36 Participants
ECOG Score 1	5 Participants n=93 Participants	4 Participants n=4 Participants	12 Participants n=27 Participants	5 Participants n=483 Participants	26 Participants n=36 Participants
ECOG Score 2	1 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants	2 Participants n=36 Participants
ECOG Score 3	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
ECOG Score 4	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants
ECOG Score 5	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants	0 Participants n=36 Participants

PRIMARY outcome

Timeframe: Day 1 or 8: 0.5-48 hours

Population: The pharmacokinetic (PK) analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter. Participants who were evaluable at a particular time point for this endpoint were included in the assessment.

Outcome measures

Outcome measures
Measure	Treatment Phase Part A: E7820 50 mg Fed n=12 Participants Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted n=14 Participants Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Treatment Phase Part A: AUC(0-inf): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for E7820	12500 nanogramhour per milliliter (nghr/mL) Standard Deviation 3510	11500 nanogramhour per milliliter (nghr/mL) Standard Deviation 3490	—	—	—

PRIMARY outcome

Timeframe: Day 1 or 8: 0.5-48 hours

Population: The PK analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter.

Outcome measures

Outcome measures
Measure	Treatment Phase Part A: E7820 50 mg Fed n=14 Participants Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted n=15 Participants Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Treatment Phase Part A: AUC(0-t): Area Under the Plasma Concentration- Time Curve From Time 0 to t for E7820	11200 ng*hr/mL Standard Deviation 3680	10500 ng*hr/mL Standard Deviation 3460	—	—	—

PRIMARY outcome

Timeframe: Day 1 or 8: 0.5-48 hours

Population: The PK analysis set included all participants who had sufficient PK data to derive at least 1 PK parameter.

Outcome measures

Outcome measures
Measure	Treatment Phase Part A: E7820 50 mg Fed n=14 Participants Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted n=15 Participants Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Treatment Phase Part A: Cmax: Maximum Observed Plasma Concentration for E7820	1030 nanogram per milliliter (ng/mL) Standard Deviation 311	901 nanogram per milliliter (ng/mL) Standard Deviation 242	—	—	—

PRIMARY outcome

Timeframe: Up to Cycle 6 (Cycle length =28 days)

Population: MTD was assessed in safety analysis set. The safety analysis set included all participants who received at least 1 dose of study drug.

MTD defined as the highest dose level at which no more than 1 of 6 participants experienced a dose-limiting toxicity(DLT), with the next higher dose having at least 2 of 3 or 2 of 6 participants experiencing DLTs. DLTs were defined using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events(CTCAE) Version 4.03 as: Neutropenia less than(\<) 0.5\*10\^9/liter(L) for greater than(\>) 5 days; neutropenia \<1\*10\^9/L with fever; thrombocytopenia \<25\*10\^9/L accompanied by bleeding or thrombocytopenia \<10\*10\^9/L; any Grade 3 or 4 nonhematological toxicity for which the study drug could not be excluded as a cause (other than nausea, vomiting or diarrhea in the absence of appropriate prophylaxis) with the following clarification: Grade 3 or 4 nonhematological laboratory abnormalities for which there was no expected clinical correlation would not be considered DLTs; treatment delay of \>14 days required to recover from E7820-related toxicities.

Outcome measures

Outcome measures
Measure	Treatment Phase Part A: E7820 50 mg Fed n=26 Participants Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Treatment Phase Part B: Maximum Tolerated Dose (MTD) of E7820 BID Dosing Schedule	50 mg	—	—	—	—

SECONDARY outcome

Timeframe: From first dose of study drug (Baseline) up to approximately 6.6 years

Population: The efficacy evaluable analysis set: all participants with a completed tumor assessment at Baseline (Chest, Abdomen and Pelvis scans) and at least 1 complete posttreatment tumor assessment (as per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1). Overall number of participants analyzed signifies participants evaluable for this measure.

BOR based on RECIST 1.1 for target and non-target lesions is complete response (CR) or partial response (PR) for \>4 weeks or stable disease (SD) for \>5 weeks from first dose. CR: disappearance of target and non-target lesions, normalization of tumor marker level, all lymph nodes must be non- pathological in size (\<10 millimeter \[mm\] short axis). PR: at least 30% decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest SOD. PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions, taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

Outcome measures

Outcome measures
Measure	Treatment Phase Part A: E7820 50 mg Fed n=13 Participants Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted n=18 Participants Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Treatment and Extension Phase Part B: E7820 60 mg n=5 Participants Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) Complete response	0 Participants	0 Participants	0 Participants	—	—
Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) Partial response	0 Participants	0 Participants	0 Participants	—	—
Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Best Overall Response (BOR) Stable disease	3 Participants	12 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: From date of first documented confirmed CR/PR until date of first documentation of PD or death (approximately up to 6.6 years)

Population: Duration of response was not analyzed since no participants had best overall response of CR or PR in the study.

Duration of response based on RECIST 1.1 for target and non-target lesions is the time from the date of first documented confirmed CR/PR until the first documentation of confirmed progressive disease (PD) or death, whichever came first. CR: disappearance of target and non-target lesions,normalization of tumor marker level,all lymph nodes must be non-pathological in size(\<10 mm short axis). PR: at least 30% decrease in SOD of target lesions,taking as reference the baseline SOD persistence of one or more non- target lesions and/or maintenance of tumor marker level above the normal limits. PD:at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions,taking as reference the smallest sum and/or unequivocal progression of existing non-target lesions and/or appearance of 1 or more new lesions.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: From first dose date to the date of the first documentation of confirmed PD or death (approximately up to 6.6 years)

Population: The efficacy evaluable set. Due to lack of available summarized data, data has been presented only descriptively in terms of number of participants who were known to have died and number of who had PD.

PD: at least 20% increase (including an absolute increase of at least 5 mm) in the SOD of target lesions. For PD: participants with best response of PD have been reported. For Death: participants with death known to have died at any point have been reported.

Outcome measures

Outcome measures
Measure	Treatment Phase Part A: E7820 50 mg Fed n=13 Participants Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted n=18 Participants Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Treatment and Extension Phase Part B: E7820 60 mg n=7 Participants Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) Death	11 Participants	14 Participants	5 Participants	—	—
Extension Phase Part A, and Treatment and Extension Phase Part B: Number of Participants With Death and Progressive Disease (PD) PD	9 Participants	6 Participants	2 Participants	—	—

SECONDARY outcome

Timeframe: From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)

Population: The safety analysis set included all participants who received at least 1 dose of study drug.

Safety assessments consisted of monitoring and recording all AEs and SAEs; regular monitoring of hematology, clinical chemistry, and urine values; physical examinations; and regular measurement of vital signs, ECG, and multiple-gated acquisition (MUGA) scans or echocardiograms.

Outcome measures

Outcome measures
Measure	Treatment Phase Part A: E7820 50 mg Fed n=15 Participants Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted n=15 Participants Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Treatment and Extension Phase Part B: E7820 60 mg n=15 Participants Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg n=19 Participants Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg n=7 Participants Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) TEAEs	7 Participants	7 Participants	15 Participants	19 Participants	7 Participants
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) SAEs	0 Participants	1 Participants	5 Participants	10 Participants	6 Participants

Adverse Events

Treatment Phase Part A: E7820 50 mg Fed

Serious events: 0 serious events

Other events: 7 other events

Deaths: 11 deaths

Treatment Phase Part A: E7820 50 mg Fasted

Serious events: 1 serious events

Other events: 6 other events

Deaths: 11 deaths

Extension Phase Part A: E7820 100 mg

Serious events: 5 serious events

Other events: 14 other events

Deaths: 11 deaths

Treatment and Extension Phase Part B: E7820 50 mg

Serious events: 10 serious events

Other events: 19 other events

Deaths: 14 deaths

Treatment and Extension Phase Part B: E7820 60 mg

Serious events: 6 serious events

Other events: 7 other events

Deaths: 5 deaths

Serious adverse events

Serious adverse events
Measure	Treatment Phase Part A: E7820 50 mg Fed n=15 participants at risk Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted n=15 participants at risk Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Extension Phase Part A: E7820 100 mg n=15 participants at risk Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg n=19 participants at risk Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg n=7 participants at risk Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Blood and lymphatic system disorders Leukopenia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Blood and lymphatic system disorders Neutropenia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Cardiac disorders Pericardial effusion	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Endocrine disorders Inappropriate antidiuretic hormone secretion	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Abdominal pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Constipation	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Duodenal ulcer haemorrhage	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Dysphagia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Nausea	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Oesophageal ulcer	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Pancreatic enzyme abnormality	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Vomiting	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Malaise	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Pyrexia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Immune system disorders Food allergy	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Bronchitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Clostridium difficile infection	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Neutropenic sepsis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Urosepsis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Hepatic enzyme abnormal	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumour haemorrhage	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Headache	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Spinal cord compression	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Rash	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Vascular disorders Orthostatic hypotension	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Muscle abscess	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Aspartate aminotransferase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Alanine aminotransferase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Ear and labyrinth disorders Tinnitus	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)

Other adverse events

Other adverse events
Measure	Treatment Phase Part A: E7820 50 mg Fed n=15 participants at risk Participants received E7820 50 mg, tablet, orally, under fed condition, once on Day 1 or Day 8 in treatment phase.	Treatment Phase Part A: E7820 50 mg Fasted n=15 participants at risk Participants received E7820 50 mg, tablet, orally, under fasted condition, once on Day 1 or Day 8 in treatment phase.	Extension Phase Part A: E7820 100 mg n=15 participants at risk Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 100 mg, once daily, tablet, orally, under fasted condition, during 28-day cycle until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 50 mg n=19 participants at risk Participants received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 50 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.	Treatment and Extension Phase Part B: E7820 60 mg n=7 participants at risk Participants received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles or early discontinuation. Participants at the end of treatment phase (who received study drug at the time of data cutoff for the primary analysis) moved on to extension phase and received E7820 60 mg, BID, tablet, orally, during each 28-day cycle for up to 6 cycles until disease progression, development of unacceptable toxicity, withdrawal of consent, or sponsor discontinuation of E7820 development.
Respiratory, thoracic and mediastinal disorders Dry throat	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Dysphonia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Psychiatric disorders Anxiety	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Psychiatric disorders Depressed mood	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Psychiatric disorders Insomnia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	31.6% 6/19 • Number of events 8 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Renal and urinary disorders Bladder spasm	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Renal and urinary disorders Haematuria	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Renal and urinary disorders Nocturia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Reproductive system and breast disorders Nipple pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Blood and lymphatic system disorders Anaemia	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	42.1% 8/19 • Number of events 19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Blood and lymphatic system disorders Leukopenia	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Blood and lymphatic system disorders Lymphopenia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Blood and lymphatic system disorders Neutropenia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Cardiac disorders Atrioventricular block	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Cardiac disorders Tachycardia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Endocrine disorders Hyperthyroidism	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Endocrine disorders Hypothyroidism	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Eye disorders Conjunctivitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Eye disorders Myopia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Eye disorders Ocular hyperaemia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Abdominal discomfort	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Abdominal distension	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Abdominal mass	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Abdominal pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	31.6% 6/19 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Abdominal pain upper	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Ascites	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Constipation	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	26.7% 4/15 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	36.8% 7/19 • Number of events 11 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	57.1% 4/7 • Number of events 5 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Diarrhoea	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	52.6% 10/19 • Number of events 12 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Dyspepsia	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	20.0% 3/15 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Dysphagia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Haematemesis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Haemorrhoids	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Mouth ulceration	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Nausea	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	26.3% 5/19 • Number of events 8 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	42.9% 3/7 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Pancreatitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Retching	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Stomatitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Tongue ulceration	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Upper gastrointestinal haemorrhage	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Gastrointestinal disorders Vomiting	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	26.3% 5/19 • Number of events 6 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Asthenia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Axillary pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Chest discomfort	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Chills	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Facial pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Fatigue	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	33.3% 5/15 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	52.6% 10/19 • Number of events 19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	57.1% 4/7 • Number of events 5 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Feeling cold	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Influenza like illness	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Local swelling	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Malaise	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Necrosis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Oedema peripheral	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Pyrexia	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	21.1% 4/19 • Number of events 6 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
General disorders Thirst	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Erysipelas	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Escherichia urinary tract infection	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Gastroenteritis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Localised infection	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Lower respiratory tract infection	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Nail infection	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Nasopharyngitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Oesophageal candidiasis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Oral candidiasis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Oral herpes	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Osteomyelitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Otitis media	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Rash pustular	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Rhinitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Skin infection	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Upper respiratory tract infection	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Infections and infestations Urinary tract infection	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	20.0% 3/15 • Number of events 5 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 5 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Injury, poisoning and procedural complications Contusion	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Injury, poisoning and procedural complications Fall	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Injury, poisoning and procedural complications Procedural hypotension	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Injury, poisoning and procedural complications Wound haemorrhage	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Alanine aminotransferase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	26.7% 4/15 • Number of events 9 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Aspartate aminotransferase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 5 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood albumin decreased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood alkaline phosphatase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 5 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood bilirubin increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	33.3% 5/15 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood cholesterol increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood creatine phosphokinase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood creatinine increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood glucose increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood lactate dehydrogenase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood magnesium decreased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood phosphorus decreased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood potassium decreased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Blood thyroid stimulating hormone increased	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Gamma-glutamyltransferase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Lipase increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Neutrophil count increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Platelet count decreased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Protein total decreased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Vitamin D decreased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations Weight decreased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	26.3% 5/19 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Investigations White blood cell count increased	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Metabolism and nutrition disorders Decreased appetite	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	26.7% 4/15 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	36.8% 7/19 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Metabolism and nutrition disorders Dehydration	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Metabolism and nutrition disorders Hyperglycaemia	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 6 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Metabolism and nutrition disorders Hypocalcaemia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Metabolism and nutrition disorders Hypokalaemia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Metabolism and nutrition disorders Hypomagnesaemia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Metabolism and nutrition disorders Hyponatraemia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Arthralgia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Back pain	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	21.1% 4/19 • Number of events 5 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Bone pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Bursitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Flank pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Joint swelling	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Musculoskeletal pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Myopathy	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Musculoskeletal and connective tissue disorders Trismus	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Cognitive disorder	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Dizziness	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	31.6% 6/19 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Dizziness postural	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Headache	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Lethargy	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	13.3% 2/15 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	36.8% 7/19 • Number of events 7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Neuralgia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Nervous system disorders Paraesthesia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Psychiatric disorders Affect lability	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 5 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Dyspnoea exertional	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 4 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Painful respiration	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Sneezing	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Respiratory, thoracic and mediastinal disorders Wheezing	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Alopecia	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Dry skin	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	20.0% 3/15 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Erythema	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Hair colour changes	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Hyperhidrosis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Nail disorder	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Night sweats	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Onychomadesis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Palmar-plantar erythrodysaesthesia syndrome	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Pruritus	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	20.0% 3/15 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Rash	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	15.8% 3/19 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Scab	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Skin fissures	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Skin and subcutaneous tissue disorders Skin lesion	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Vascular disorders Haematoma	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/19 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	14.3% 1/7 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Vascular disorders Haemorrhage	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Vascular disorders Hypertension	6.7% 1/15 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	10.5% 2/19 • Number of events 2 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	28.6% 2/7 • Number of events 3 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Vascular disorders Hypotension	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Vascular disorders Orthostatic hypotension	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)
Vascular disorders Phlebitis	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/15 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	5.3% 1/19 • Number of events 1 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)	0.00% 0/7 • From the first dose of study drug up to 30 days after the last dose of study drug (approximately up to 6.6 years)

Additional Information

Eisai Medical Information

Eisai, Inc.

Phone: +1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place