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Clinical Trial Results:
Phase 1/2 Open-Label Study of the Safety, Pharmacokinetics, and Preliminary Activity of ASTX295 in Subjects with Wild-Type TP53 Advanced Solid Tumors

Summary
EudraCT number	2021-005033-16
Trial protocol	DE FR ES IT
Global end of trial date	15 Aug 2024

Results information
Results version number	v1(current)
This version publication date	05 Jun 2025
First version publication date	05 Jun 2025
Other versions

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

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Trial information

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Sponsor protocol code

ASTX295-01

ISRCTN number

US NCT number

NCT03975387

WHO universal trial number (UTN)

Sponsor organisation name

Taiho Oncology, Inc.

Sponsor organisation address

101 Carnegie Center, Suite 101, Princeton, NJ, United States, 08540

Public contact

Senior Study Manager, Taiho Oncology, Inc., , 1 844-878-2446, medicalinformation@taihooncology.com

Scientific contact

Senior Study Manager, Taiho Oncology, Inc., +1 844-878-2446, medicalinformation@taihooncology.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

15 Aug 2024

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Aug 2024

Was the trial ended prematurely?

Yes

Main objective of the trial

The main objective of this study was to assess safety and tolerability of ASTX295 including determination of maximum tolerated dose (MTD), and/or recommended dose for expansion (RDE) in Phase 1a (dose escalation) part of the study, and to determine the recommended Phase 2 dose (RP2D) and regimen of ASTX295 in Phase 1b (dose expansion) part of the study.

Protection of trial subjects

All study subjects were required to read and sign an Informed Consent Form (ICF).

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Jul 2019

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 106

Worldwide total number of subjects

106

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Subjects were enrolled at 11 sites in the United States from 05 July 2019 to 15 August 2024.

Screening details

A total of 106 subjects with wild-type TP53 advanced solid tumors were enrolled to receive ASTX295 in Phase 1 which consisted of 2 parts: Phase 1a (dose escalation) and Phase 1b (dose expansion). Phase 2 part of the study was terminated by the sponsor's strategic decision.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Dose Escalation: Phase 1a: Cohort 1

Arm description

Subjects received ASTX295 at starting dose of 15 milligrams (mg), orally, administered once daily (QD) in each 28-day cycle under fasted condition, up to a maximum of 1.8 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 15 mg, administered QD in each 28-day cycle up to a maximum of 1.8 months.

Dose Escalation: Phase 1a: Cohort 2

Arm description

Subjects received ASTX295 at an oral dose of 45 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 17.4 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 45 mg, administered QD in each 28-day cycle up to a maximum of 17.4 months.

Dose Escalation: Phase 1a: Cohort 3

Arm description

Subjects received ASTX295 at an oral dose of 120 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 1.8 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 120 mg, administered QD in each 28-day cycle up to a maximum of 1.8 months.

Dose Escalation: Phase 1a: Cohort 4

Arm description

Subjects received ASTX295 at an oral dose of 240 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 6.4 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 240 mg, administered QD in each 28-day cycle up to a maximum of 6.4 months.

Dose Escalation: Phase 1a: Cohort 5

Arm description

Subjects received ASTX295 at an oral dose of 420 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 14.7 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 240 mg, administered QD in each 28-day cycle up to a maximum of 14.7 months.

Dose Escalation: Phase 1a: Cohort 6

Arm description

Subjects received ASTX295 at an oral dose of 520 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 42.4 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 520 mg, administered QD in each 28-day cycle up to a maximum of 42.4 months.

Dose Escalation: Phase 1a: Cohort 7

Arm description

Subjects received ASTX295 at an oral dose of 415 mg, administered QD in each 28-day cycle under fed state, up to a maximum of 22.5 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 415 mg, administered QD in each 28-day cycle up to a maximum of 22.5 months.

Dose Escalation: Phase 1a: Cohort 8

Arm description

Subjects received ASTX295 at an oral dose of 200 mg, administered twice daily (BID) in each 28-day cycle under fasted condition, up to a maximum of 17.4 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 200 mg, administered BID in each 28-day cycle up to a maximum of 17.4 months.

Dose Escalation: Phase 1a: Cohort 9

Arm description

Subjects received ASTX295 at an oral dose of 320 mg, administered BID in each 28-day cycle under fasted condition, up to a maximum of 27.5 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 320 mg, administered BID in each 28-day cycle up to a maximum of 27.5 months.

Dose Escalation: Phase 1a: Cohort 10

Arm description

Subjects received ASTX295 at an oral dose of 520 mg (5 days on, 2 days off), administered QD in each 28-day cycle, with or without food, up to a maximum of 12 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 520 mg, administered QD, in each 28-day cycle up to a maximum of 12 months.

Dose Escalation: Phase 1a: Cohort 11

Arm description

Subjects received ASTX295 at an oral dose of 520 mg (3 days on, 4 days off), administered QD in each 28-day cycle, with or without food, up to a maximum of 1.8 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 520 mg, administered QD in each 28-day cycle up to a maximum of 1.8 months.

Dose Escalation: Phase 1a: Cohort 12

Arm description

Subjects received ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 11.7 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle up to a maximum of 11.7 months.

Dose Escalation: Phase 1a: Cohort 13

Arm description

Subjects received ASTX295 at an oral dose of 660 mg (3 days on, 4 days off), administered QD, in each 28-day cycle, with or without food, up to a maximum of 18.5 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 660 mg, administered QD in each 28-day cycle up to a maximum of 18.5 months.

Dose Escalation: Phase 1a: Cohort 14

Arm description

Subjects received ASTX295 at an oral dose of 800 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 6 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 800 mg, administered QD, twice a week, in each 28-day cycle up to a maximum of 6 months.

Dose Expansion: Phase 1b: Cohort 1

Arm description

Subjects received ASTX295 at an oral dose of 400 mg, administered daily, in each 28-day cycle, with or without food, up to a maximum of 14.7 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 400 mg, administered daily, in each 28-day cycle up to a maximum of 14.7 months.

Dose Expansion: Phase 1b: Cohort 2

Arm description

Subjects received ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 14.2 months.

Arm type

Experimental

Investigational medicinal product name

ASTX295

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle up to a maximum of 14.2 months.

Number of subjects in period 1	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 7	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Started	1	3	4	4	9	8	5	6	7	8	4	9	8	6	12	12
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	1	3	4	4	9	8	5	6	7	8	4	9	8	6	12	12
Death	1	-	2	2	4	6	3	4	3	6	4	6	5	5	4	3
Complete Consent Withdrawal	-	1	2	-	1	1	1	1	2	-	-	-	-	1	-	1
Study Terminated by Sponsor	-	1	-	1	2	1	1	1	2	2	-	2	2	-	7	7
Lost to follow-up	-	1	-	1	2	-	-	-	-	-	-	1	1	-	1	1

Baseline characteristics

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Reporting group title

Dose Escalation: Phase 1a: Cohort 1

Reporting group description

Subjects received ASTX295 at starting dose of 15 milligrams (mg), orally, administered once daily (QD) in each 28-day cycle under fasted condition, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 2

Reporting group description

Subjects received ASTX295 at an oral dose of 45 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 17.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 3

Reporting group description

Subjects received ASTX295 at an oral dose of 120 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 4

Reporting group description

Subjects received ASTX295 at an oral dose of 240 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 6.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 5

Reporting group description

Subjects received ASTX295 at an oral dose of 420 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 14.7 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 6

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 42.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 7

Reporting group description

Subjects received ASTX295 at an oral dose of 415 mg, administered QD in each 28-day cycle under fed state, up to a maximum of 22.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 8

Reporting group description

Subjects received ASTX295 at an oral dose of 200 mg, administered twice daily (BID) in each 28-day cycle under fasted condition, up to a maximum of 17.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 9

Reporting group description

Subjects received ASTX295 at an oral dose of 320 mg, administered BID in each 28-day cycle under fasted condition, up to a maximum of 27.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 10

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg (5 days on, 2 days off), administered QD in each 28-day cycle, with or without food, up to a maximum of 12 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 11

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg (3 days on, 4 days off), administered QD in each 28-day cycle, with or without food, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 12

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 11.7 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 13

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg (3 days on, 4 days off), administered QD, in each 28-day cycle, with or without food, up to a maximum of 18.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 14

Reporting group description

Subjects received ASTX295 at an oral dose of 800 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 6 months.

Reporting group title

Dose Expansion: Phase 1b: Cohort 1

Reporting group description

Subjects received ASTX295 at an oral dose of 400 mg, administered daily, in each 28-day cycle, with or without food, up to a maximum of 14.7 months.

Reporting group title

Dose Expansion: Phase 1b: Cohort 2

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 14.2 months.

Reporting group values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 7	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2	Total
Number of subjects	1	3	4	4	9	8	5	6	7	8	4	9	8	6	12	12	106
Age categorical
Units: Subjects
In utero																	0
Preterm newborn infants (gestational age < 37 wks)																	0
Newborns (0-27 days)																	0
Infants and toddlers (28 days-23 months)																	0
Children (2-11 years)																	0
Adolescents (12-17 years)																	0
Adults (18-64 years)																	0
From 65-84 years																	0
85 years and over																	0
Age continuous
Here, for Dose Escalation: Phase 1a: Cohort 1, "99999" represents that data for standard deviation could not be collected as only 1 subject was present in the cohort.
Units: years
arithmetic mean (standard deviation)	41.0 ( 99999 )	60.3 ( 2.31 )	55.3 ( 10.78 )	63.8 ( 7.04 )	65.6 ( 6.67 )	61.0 ( 8.30 )	62.0 ( 12.90 )	57.2 ( 14.47 )	57.9 ( 15.48 )	57.6 ( 11.55 )	60.8 ( 4.35 )	52.1 ( 16.84 )	67.6 ( 12.70 )	60.3 ( 11.09 )	61.0 ( 12.25 )	58.4 ( 16.82 )	-
Gender categorical
Units: Subjects
Female	0	1	1	2	3	2	4	3	3	4	2	4	5	3	8	9	54
Male	1	2	3	2	6	6	1	3	4	4	2	5	3	3	4	3	52
Race
Units: Subjects
Asian	0	0	1	0	0	0	1	0	0	0	0	0	0	0	0	2	4
American Indian or Alaska Native	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Black or African American	0	0	0	1	0	1	0	1	0	2	1	1	1	1	0	0	9
Native Hawaiian	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
White	1	3	2	2	9	7	4	4	6	5	3	6	7	5	12	9	85
Other	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	2
Not Reported	0	0	1	1	0	0	0	1	0	0	0	0	0	0	0	1	4
Unknown	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Ethnicity
Units: Subjects
Hispanic or Latino	1	0	1	1	1	2	1	1	1	0	1	3	0	1	0	2	16
Not Hispanic or Latino	0	3	3	3	8	5	3	4	6	7	3	6	8	4	12	9	84
Not Reported	0	0	0	0	0	0	1	1	0	0	0	0	0	1	0	1	4
Unknown	0	0	0	0	0	1	0	0	0	1	0	0	0	0	0	0	2

End points

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Reporting group title

Dose Escalation: Phase 1a: Cohort 1

Reporting group description

Subjects received ASTX295 at starting dose of 15 milligrams (mg), orally, administered once daily (QD) in each 28-day cycle under fasted condition, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 2

Reporting group description

Subjects received ASTX295 at an oral dose of 45 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 17.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 3

Reporting group description

Subjects received ASTX295 at an oral dose of 120 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 4

Reporting group description

Subjects received ASTX295 at an oral dose of 240 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 6.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 5

Reporting group description

Subjects received ASTX295 at an oral dose of 420 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 14.7 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 6

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 42.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 7

Reporting group description

Subjects received ASTX295 at an oral dose of 415 mg, administered QD in each 28-day cycle under fed state, up to a maximum of 22.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 8

Reporting group description

Subjects received ASTX295 at an oral dose of 200 mg, administered twice daily (BID) in each 28-day cycle under fasted condition, up to a maximum of 17.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 9

Reporting group description

Subjects received ASTX295 at an oral dose of 320 mg, administered BID in each 28-day cycle under fasted condition, up to a maximum of 27.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 10

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg (5 days on, 2 days off), administered QD in each 28-day cycle, with or without food, up to a maximum of 12 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 11

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg (3 days on, 4 days off), administered QD in each 28-day cycle, with or without food, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 12

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 11.7 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 13

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg (3 days on, 4 days off), administered QD, in each 28-day cycle, with or without food, up to a maximum of 18.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 14

Reporting group description

Subjects received ASTX295 at an oral dose of 800 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 6 months.

Reporting group title

Dose Expansion: Phase 1b: Cohort 1

Reporting group description

Subjects received ASTX295 at an oral dose of 400 mg, administered daily, in each 28-day cycle, with or without food, up to a maximum of 14.7 months.

Reporting group title

Dose Expansion: Phase 1b: Cohort 2

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 14.2 months.

Primary: Phase 1a and 1b: Number of Subjects with Treatment Emergent Adverse Events (TEAEs), and Serious TEAEs

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End point title

Phase 1a and 1b: Number of Subjects with Treatment Emergent Adverse Events (TEAEs), and Serious TEAEs ^[1]

End point description

An adverse event (AE) is any untoward medical occurrence in a subject or clinical study subject, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs are defined as events that first occur or worsen on or after the date of the first study treatment Cycle 1 Day 1 (C1D1) until 30 days after the last dose of study treatment. Serious TEAE is defined as any untoward medical occurrence that, at any dose result in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, or is a congenital anomaly/birth defect. Safety analysis set included all subjects who received at least one dose of study drug.

End point type

Primary

End point timeframe

Up to approximately 61.3 months

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

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 7	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	1	3	4	4	9	8	5	6	7	8	4	9	8	6	12	12
Units: subjects
TEAEs	1	3	4	4	9	8	5	6	7	8	4	9	8	6	12	12
SAEs	0	0	2	0	2	1	1	2	0	1	0	4	1	4	6	4

No statistical analyses for this end point

Primary: Phase 1a: Number of Subjects with Dose-limiting Toxicities (DLTs)

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End point title

Phase 1a: Number of Subjects with Dose-limiting Toxicities (DLTs) ^[2] ^[3]

End point description

Dose-limiting toxicities (DLTs) were AEs graded by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version 5.0 criteria that occurred during first cycle of treatment & represent any 1 of the following: grade 4 thrombocytopenia of any duration; grade 3 thrombocytopenia lasting more than 7 days; ≥grade 3 hematologic toxicity with complications; febrile neutropenia of any duration; grade 4 neutropenia lasting more than 5 days; liver-associated abnormalities; ≥grade 3 nonhematologic AE; event leading to unacceptable risk after dose escalation as suggested by data and safety review committee (DSRC); clinically significant toxicities that persist or occur beyond Cycle 1. Dose escalation evaluable population included all subjects in the dose escalation who either experienced a DLT during the first cycle of treatment, or who completed the first cycle without experiencing a DLT and with at least 85% of planned study treatments administered.

End point type

Primary

End point timeframe

During Cycle 1 (cycle length= 28 days)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Descriptive statistics were provided for this endpoint.
[3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 7	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14
Number of subjects analysed	1	3	4	4	9	8	5	6	7	8	4	9	8	6
Units: subjects
DLTs	0	0	0	0	0	1	1	1	2	2	0	0	0	0

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Disease Control Rate (DCR)

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End point title

Phase 1a and 1b: Disease Control Rate (DCR)

End point description

DCR was defined as proportion of subjects who have a complete response (CR), partial response (PR)/stable disease at Week 16 according to response evaluation criteria in solid tumors (RECIST) 1.1/modified RECIST (mRECIST) 1.1 (for malignant pleural mesothelioma [MPM]) as assessed by investigator. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR: At least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters. Stable disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease, taking as reference smallest sum diameters while on study. Efficacy analysis set included all subjects who received any amount of study treatment. DCR was based on subjects who were in this set & who had disease assessment at baseline & at least 1 follow-up disease assessment/subjects who died/stopped treatment.

End point type

Secondary

End point timeframe

Up to approximately 61.3 months

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 7	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	1	3	3	4	8	8	5	5	4	7	4	8	7	5	11	10
Units: percentage of subjects
number (not applicable)	100	100	0	75.0	62.5	75.0	80.0	80.0	50.0	71.4	25.0	75.0	71.4	60.0	72.7	50.0

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Objective Response Rate (ORR)

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End point title

Phase 1a and 1b: Objective Response Rate (ORR)

End point description

ORR was defined as the proportion of subjects whose best response was CR or PR according to RECIST 1.1 or mRECIST 1.1 (for MPM) as assessed by the investigator. CR: Disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Efficacy analysis set included all subjects who received any amount of study treatment. ORR was based on subjects who were in this set & who had disease assessment at baseline and at least 1 follow-up disease assessment or subjects who died or stopped treatment before the first scheduled disease assessment due to clinical progression or toxicity.

End point type

Secondary

End point timeframe

Up to approximately 61.3 months

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 7	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	1	3	3	4	8	8	5	5	4	7	4	8	7	5	11	10
Units: percentage of subjects
number (not applicable)	0	0	0	0	12.5	12.5	0	0	0	0	0	12.5	0	0	0	0

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of ASTX295

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End point title

Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of ASTX295 ^[4]

End point description

PK analysis set included all subjects who received the study drug and have post baseline plasma concentration data. Here, '99999' indicates that values were not measurable due to low number of subjects for the specified arms. ‘Subjects analysed’ indicates number of subjects with data available for analyses and 'n’ indicates number of subjects with data available for analyses at the specified timepoint.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	1	3	4	4	9	8	5	7	8	4	9	8	6	12	12
Units: hoursnanograms/millilitres (hng/mL)
geometric mean (geometric coefficient of variation)
C1D1 (n=1,3,4,4,9,8,5,5,7,8,4,9,8,6,12,12)	28.7 ( 99999 )	60.0 ( 81.8 )	1230 ( 222.2 )	1140 ( 50.7 )	3850 ( 135.8 )	3500 ( 140.7 )	844 ( 82.8 )	2180 ( 133.1 )	11200 ( 145.8 )	3270 ( 64.4 )	10600 ( 161.2 )	7870 ( 222.9 )	9310 ( 102.1 )	3020 ( 72.4 )	11600 ( 200.3 )
C2D1 (n=1,3,2,3,7,5,1,5,2,7,3,6,6,4,11,9)	24.6 ( 99999 )	113 ( 82.8 )	1480 ( 77.2 )	2270 ( 34.7 )	3540 ( 58.7 )	1710 ( 180.2 )	1790 ( 28.2 )	4600 ( 65.3 )	12700 ( 131.5 )	2890 ( 40.2 )	10500 ( 237.4 )	8640 ( 186.7 )	11000 ( 52.2 )	4440 ( 50.9 )	4730 ( 262.4 )

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Maximum Observed Plasma Concentration (Cmax) of ASTX295

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End point title

Phase 1a and 1b: Maximum Observed Plasma Concentration (Cmax) of ASTX295 ^[5]

End point description

PK analysis set included all subjects who received the study drug and have post baseline plasma concentration data. Here, '99999' indicates that dispersion values were not measurable due to low number of subjects for the specified arms. ‘Subjects analysed’ indicates number of subjects with data available for analyses and ‘n’ indicates number of subjects with data available for analyses at the specified timepoint.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	1	3	4	4	9	8	5	7	8	4	9	8	6	12	12
Units: nanogram(s)/millilitre (ng/mL)
geometric mean (geometric coefficient of variation)
C1D1 (n=1,3,4,4,9,8,5,7,8,4,9,8,6,12,12)	19.1 ( 99999 )	27.3 ( 9.2 )	367 ( 189.9 )	448 ( 69.7 )	963 ( 109.0 )	758 ( 224.2 )	307 ( 67.6 )	924 ( 123.5 )	2670 ( 133.0 )	936 ( 70.9 )	2210 ( 189.7 )	1830 ( 228.8 )	2600 ( 90.3 )	786 ( 63.0 )	3010 ( 207.2 )
C2D1 (n=1,3,2,3,7,5,5,2,7,4,5,6,4,11,9)	15.3 ( 99999 )	40.4 ( 108.1 )	318 ( 49.7 )	937 ( 63.3 )	963 ( 81.8 )	497 ( 196.3 )	544 ( 52.2 )	1800 ( 54.8 )	2870 ( 87.6 )	1010 ( 89.3 )	1620 ( 334 )	2100 ( 165.2 )	3490 ( 53.8 )	942 ( 50.8 )	1370 ( 192.1 )

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Minimum Observed Plasma Concentration (Cmin) of ASTX295

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End point title

Phase 1a and 1b: Minimum Observed Plasma Concentration (Cmin) of ASTX295 ^[6]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	1	3	2	3	7	7	5	2	7	4	7	6	5	11	10
Units: ng/mL
geometric mean (geometric coefficient of variation)
C2D1	99999 ( 99999 )	99999 ( 99999 )	14.17 ( 151.8 )	33.56 ( 48.7 )	40.00 ( 67.3 )	99999 ( 99999 )	59.04 ( 64.0 )	129.4 ( 6.0 )	134 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	99999 ( 99999 )	14.44 ( 113.3 )	99999 ( 99999 )	26.78 ( 256.5 )

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Time to Maximum Observed Plasma Concentration (Tmax) of ASTX295

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End point title

Phase 1a and 1b: Time to Maximum Observed Plasma Concentration (Tmax) of ASTX295 ^[7]

End point description

PK analysis set included all subjects who received the study drug and have post baseline plasma concentration data. Here, '99999' indicates that dispersion values were not measurable due to low number of subjects for the specified arms. 'Subjects analysed’ indicates number of subjects with data available for analyses and ‘n’ indicates number of subjects with data available for analyses at the specified timepoint.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

Dose Escalation: Phase 1a: Cohort 1

Dose Escalation: Phase 1a: Cohort 2

Dose Escalation: Phase 1a: Cohort 3

Dose Escalation: Phase 1a: Cohort 4

Dose Escalation: Phase 1a: Cohort 5

Dose Escalation: Phase 1a: Cohort 6

Dose Escalation: Phase 1a: Cohort 8

Dose Escalation: Phase 1a: Cohort 9

Dose Escalation: Phase 1a: Cohort 10

Dose Escalation: Phase 1a: Cohort 11

Dose Escalation: Phase 1a: Cohort 12

Dose Escalation: Phase 1a: Cohort 13

Dose Escalation: Phase 1a: Cohort 14

Dose Expansion: Phase 1b: Cohort 1

Dose Expansion: Phase 1b: Cohort 2

Number of subjects analysed

Units: hours

median (full range (min-max))

C1D1 (n=1,3,4,4,9,8,5,5,7,8,4,9,8,6,12,12)

0.95 (-99999 to 99999)

1.00 (1.00 to 3.83)

1.52 (1.00 to 3.83)

1.47 (1.00 to 2.00)

3.95 (2.00 to 4.00)

3.01 (2.93 to 4.15)

2.97 (1.98 to 5.7)

3.02 (2.13 to 4.17)

3.00 (0.52 to 6.03)

2.46 (1.00 to 3.17)

2.98 (1.02 to 6.00)

2.93 (1.98 to 5.85)

3.49 (1.98 to 3.97)

3.42 (0.97 to 6.02)

2.92 (1.02 to 5.77)

C2D1 (n=1,3,2,3,7,5,1,5,2,7,4,6,6,4,11,9)

1.00 (-99999 to 99999)

3.08 (0.50 to 3.92)

1.51 (1.00 to 2.02)

2.83 (1.97 to 2.90)

2.85 (2.00 to 3.02)

3.02 (1.00 to 4.03)

2.90 (2.05 to 3.88)

2.42 (2.17 to 2.67)

3.05 (2.07 to 5.67)

2.55 (1.97 to 3.22)

3.48 (2.00 to 4.05)

3.45 (1.98 to 5.9)

3.39 (1.98 to 3.98)

3.00 (1.02 to 5.98)

2.97 (1.92 to 5.82)

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Elimination Half-life (t1/2) of ASTX295

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End point title

Phase 1a and 1b: Elimination Half-life (t1/2) of ASTX295 ^[8]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	0 ^[9]	1	2	4	5	7	3	3	6	4	6	7	6	7	9
Units: hours
geometric mean (geometric coefficient of variation)
C1D1 (n=0,0,2,4,5,7,3,3,3,6,4,6,7,6,7,9)	( )	99999 ( 99999 )	3.14 ( 37.8 )	2.42 ( 68.9 )	4.50 ( 35.0 )	4.86 ( 66.4 )	1.73 ( 39.5 )	1.35 ( 16.7 )	3.74 ( 74.9 )	5.55 ( 15.1 )	4.39 ( 28.8 )	5.10 ( 39.6 )	3.52 ( 60.0 )	4.99 ( 58.8 )	3.32 ( 58.3 )
C2D1 (n=0,1,2,2,6,4,0,1,2,4,3,3,4,4,7,5)	( )	3.14 ( 99999 )	7.86 ( 46.7 )	4.46 ( 268.9 )	4.50 ( 106.4 )	3.81 ( 52.3 )	1.93 ( 99999 )	2.49 ( 68.4 )	3.59 ( 116.8 )	8.06 ( 3.6 )	4.48 ( 19.8 )	4.44 ( 20.0 )	3.60 ( 14.4 )	6.01 ( 18.7 )	4.20 ( 23.2 )

Notes
[9] - Data was not reported as no subjects were available for analyses at the specified timepoint.

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX295

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End point title

Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX295 ^[10]

End point description

Pharmacokinetics (PK) analysis set included all subjects who received the study drug and have post baseline plasma concentration data. Here, C1D1 represents Cycle 1 Day 1, and C2D1 represents Cycle 2 Day 1, '99999' indicates that values were not measurable due to low number of subjects for the specified arms. ‘Subjects analysed’ indicates number of subjects with data available for analyses and ‘n’ indicates number of subjects with data available for analyses at the specified timepoint.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	1	0 ^[11]	4	4	9	8	0 ^[12]	0 ^[13]	8	4	8	8	6	12	12
Units: hoursnanograms/millilitres (hng/mL)
geometric mean (geometric coefficient of variation)
C1D1 (n=0,0,3,3,7,8,5,0,0,8,4,8,8,6,11,12)	99999 ( 99999 )	( )	2040 ( 148.9 )	1380 ( 53.6 )	4450 ( 59.0 )	3520 ( 140.5 )	( )	( )	11300 ( 137.8 )	3280 ( 64.4 )	11500 ( 173.4 )	7860 ( 223.2 )	9360 ( 101.3 )	2930 ( 74.3 )	11800 ( 195.7 )
C2D1 (n=1,0,2,2,7,4,0,0,0,7,3,6,4,4,9,6)	27.7 ( 99999 )	( )	1500 ( 76.3 )	2170 ( 39.8 )	3610 ( 60.4 )	2760 ( 82.8 )	( )	( )	12700 ( 129.8 )	2890 ( 40.2 )	10500 ( 238.6 )	10400 ( 175.0 )	11000 ( 52.5 )	4180 ( 52.6 )	8940 ( 203.4 )

Notes
[11] - Data was not reported as AUC(0-24) could not be calculated.
[12] - Since this cohort was dosed every 12 hours, therefore AUC0-24 could not be calculated.
[13] - Since this cohort was dosed every 12 hours, therefore AUC0-24 could not be calculated.

No statistical analyses for this end point

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of ASTX295

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End point title

Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of ASTX295 ^[14]

End point description

PK analysis set included all subjects who received the study drug and have post baseline plasma concentration data. Here, '99999' indicates that values were not measurable due to low number of subjects for the specified arms. ‘Subjects analysed’ indicates number of subjects with data available for analyses and ‘n’ indicates number of subjects with data available for analyses at the specified timepoint.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Number of subjects analysed	0 ^[15]	1	4	4	9	8	5	7	8	4	9	8	6	12	12
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n=0,0,2,4,5,7,3,3,3,6,4,6,7,6,7,9)	( )	99999 ( 99999 )	1550 ( 986.8 )	1250 ( 42.5 )	3670 ( 40.8 )	3300 ( 138.5 )	1190 ( 43.0 )	4350 ( 211.2 )	13000 ( 190.6 )	3380 ( 63.3 )	10200 ( 215.9 )	9680 ( 221.2 )	9540 ( 101.0 )	2390 ( 74.6 )	13500 ( 176.3 )
C2D1 (n=0,1,2,2,6,4,0,1,2,4,3,3,4,4,7,5)	( )	261 ( 99999 )	1660 ( 90.1 )	2330 ( 51.5 )	4400 ( 50.6 )	2820 ( 83.3 )	2160 ( 99999 )	5250 ( 49.4 )	16700 ( 112.8 )	3150 ( 36.1 )	13500 ( 75.4 )	10800 ( 179.3 )	11200 ( 51.8 )	4590 ( 46.1 )	12400 ( 169.9 )

Notes
[15] - Data was not reported as no subjects were available for analyses at the specified timepoint.

No statistical analyses for this end point

Secondary: Phase 1a: AUC0-24 of ASTX295 Under Fed State

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End point title

Phase 1a: AUC0-24 of ASTX295 Under Fed State ^[16]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 7
Number of subjects analysed	5
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n=5)	5730 ( 57.9 )
C2D1 (n=0)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Phase 1a: AUClast of ASTX295 Under Fed State

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End point title

Phase 1a: AUClast of ASTX295 Under Fed State ^[17]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 7
Number of subjects analysed	5
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n=5)	5720 ( 58.3 )
C2D1 (n=1)	427 ( 99999 )

No statistical analyses for this end point

Secondary: Phase 1a: AUC0-inf of ASTX295 Under Fed State

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End point title

Phase 1a: AUC0-inf of ASTX295 Under Fed State ^[18]

End point description

PK analysis set included all subjects who received the study drug and have post baseline plasma concentration data. Here, '99999' indicates that values were not measurable due to low number of subjects for the specified arms. ‘Subjects analysed’ indicates number of subjects with data available for analyses and ‘n’ indicates number of subjects with data available for analyses at the specified timepoint.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 7
Number of subjects analysed	5
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n=3)	7200 ( 26.9 )
C2D1 (n=0)	99999 ( 99999 )

No statistical analyses for this end point

Secondary: Phase 1a: Cmax of ASTX295 Under Fed State

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End point title

Phase 1a: Cmax of ASTX295 Under Fed State ^[19]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 7
Number of subjects analysed	5
Units: ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n=5)	1970 ( 88.4 )
C2D1 (n=1)	43.1 ( 99999 )

No statistical analyses for this end point

Secondary: Phase 1a: Cmin of ASTX295 Under Fed State

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End point title

Phase 1a: Cmin of ASTX295 Under Fed State ^[20]

End point description

PK analysis set included all subjects who received the study drug and have post baseline plasma concentration data. Here, '99999' indicates that dispersion values were not measurable due to low number of subjects. ‘Subjects analysed’ indicates number of subjects with data available for analyses.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 7
Number of subjects analysed	1
Units: ng/mL
geometric mean (geometric coefficient of variation)
C2D1	5.88 ( 99999 )

No statistical analyses for this end point

Secondary: Phase 1a: Tmax of ASTX295 Under Fed State

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End point title

Phase 1a: Tmax of ASTX295 Under Fed State ^[21]

End point description

PK analysis set included all subjects who received the study drug and have post baseline plasma concentration data. Here, '99999' indicates that dispersion values were not measurable due to low number of subjects for the specified arms. 'Subjects analysed’ indicates number of subjects with data available for analyses and ‘n’ indicates number of subjects with data available for analyses at the specified timepoint.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 7
Number of subjects analysed	5
Units: hours
median (full range (min-max))
C1D1 (n=5)	3.87 (1.02 to 4.17)
C2D1 (n=1)	7.33 (-99999 to 99999)

No statistical analyses for this end point

Secondary: Phase 1a: The t1/2 of ASTX295 Under Fed State

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End point title

Phase 1a: The t1/2 of ASTX295 Under Fed State ^[22]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 and Day 2 of Cycles 1 and 2, and at multiple timepoints post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 28 days).

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Descriptive statistics were provided for this endpoint.

End point values	Dose Escalation: Phase 1a: Cohort 7
Number of subjects analysed	3
Units: hours
geometric mean (geometric coefficient of variation)
C1D1 (n=3)	6.55 ( 36.7 )
C2D1 (n=0)	99999 ( 99999 )

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Up to approximately 61.3 months

Adverse event reporting additional description

Safety analysis set included all subjects who received at least one dose of study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

Dose Escalation: Phase 1a: Cohort 1

Reporting group description

Subjects received ASTX295 at starting dose of 15 milligrams (mg), orally, administered once daily (QD) in each 28-day cycle under fasted condition, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 2

Reporting group description

Subjects received ASTX295 at an oral dose of 45 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 17.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 3

Reporting group description

Subjects received ASTX295 at an oral dose of 120 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 4

Reporting group description

Subjects received ASTX295 at an oral dose of 240 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 6.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 5

Reporting group description

Subjects received ASTX295 at an oral dose of 420 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 14.7 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 6

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg, administered QD in each 28-day cycle under fasted condition, up to a maximum of 42.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 7

Reporting group description

Subjects received ASTX295 at an oral dose of 415 mg, administered QD in each 28-day cycle under fed state, up to a maximum of 22.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 8

Reporting group description

Subjects received ASTX295 at an oral dose of 200 mg, administered twice daily (BID) in each 28-day cycle under fasted condition, up to a maximum of 17.4 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 9

Reporting group description

Subjects received ASTX295 at an oral dose of 320 mg, administered BID in each 28-day cycle under fasted condition, up to a maximum of 27.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 10

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg (5 days on, 2 days off), administered QD in each 28-day cycle, with or without food, up to a maximum of 12 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 11

Reporting group description

Subjects received ASTX295 at an oral dose of 520 mg (3 days on, 4 days off), administered QD in each 28-day cycle, with or without food, up to a maximum of 1.8 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 12

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 11.7 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 13

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg (3 days on, 4 days off), administered QD, in each 28-day cycle, with or without food, up to a maximum of 18.5 months.

Reporting group title

Dose Escalation: Phase 1a: Cohort 14

Reporting group description

Subjects received ASTX295 at an oral dose of 800 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 6 months.

Reporting group title

Dose Expansion: Phase 1b: Cohort 1

Reporting group description

Subjects received ASTX295 at an oral dose of 400 mg, administered daily, in each 28-day cycle, with or without food, up to a maximum of 14.7 months.

Reporting group title

Dose Expansion: Phase 1b: Cohort 2

Reporting group description

Subjects received ASTX295 at an oral dose of 660 mg, administered QD, twice a week, in each 28-day cycle, with or without food, up to a maximum of 14.2 months.

Dose Escalation: Phase 1a: Cohort 1

Dose Escalation: Phase 1a: Cohort 2

Dose Escalation: Phase 1a: Cohort 3

Dose Escalation: Phase 1a: Cohort 4

Dose Escalation: Phase 1a: Cohort 5

Dose Escalation: Phase 1a: Cohort 6

Dose Escalation: Phase 1a: Cohort 7

Dose Escalation: Phase 1a: Cohort 8

Dose Escalation: Phase 1a: Cohort 9

Dose Escalation: Phase 1a: Cohort 10

Dose Escalation: Phase 1a: Cohort 11

Dose Escalation: Phase 1a: Cohort 12

Dose Escalation: Phase 1a: Cohort 13

Dose Escalation: Phase 1a: Cohort 14

Dose Expansion: Phase 1b: Cohort 1

Dose Expansion: Phase 1b: Cohort 2

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

2 / 4 (50.00%)

0 / 4 (0.00%)

2 / 9 (22.22%)

1 / 8 (12.50%)

1 / 5 (20.00%)

2 / 6 (33.33%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 4 (0.00%)

4 / 9 (44.44%)

1 / 8 (12.50%)

4 / 6 (66.67%)

6 / 12 (50.00%)

4 / 12 (33.33%)

number of deaths (all causes)

number of deaths resulting from adverse events

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Injury, poisoning and procedural complications

Fall

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal wall wound

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Hypotension

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrial fibrillation

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pericardial effusion

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Loss of consciousnes

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Seizure

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hemiparesis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 8 (12.50%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Asthenia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

1 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Oedema

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

1 / 5 (20.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Small intestinal obstruction

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

1 / 5 (20.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

1 / 6 (16.67%)

1 / 12 (8.33%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal pain

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Oesophageal obstruction

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemoperitoneum

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hepatobiliary disorders

Hyperbilirubinaemia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

1 / 8 (12.50%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Haemoptysis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Dyspnoea

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Tracheal fistula

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

1 / 6 (16.67%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

2 / 12 (16.67%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

2 / 12 (16.67%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Renal haemorrhage

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

1 / 12 (8.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Infections and infestations

Pneumonia

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

1 / 4 (25.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

1 / 8 (12.50%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

1 / 6 (16.67%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

0 / 1

0 / 0

Abdominal abscess

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Septic shock

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

1 / 9 (11.11%)

0 / 8 (0.00%)

0 / 6 (0.00%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Skin bacterial infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Urosepsis

subjects affected / exposed

0 / 1 (0.00%)

0 / 3 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 5 (0.00%)

0 / 6 (0.00%)

0 / 7 (0.00%)

0 / 8 (0.00%)

0 / 4 (0.00%)

0 / 9 (0.00%)

0 / 8 (0.00%)

0 / 6 (0.00%)

1 / 12 (8.33%)

0 / 12 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Dose Escalation: Phase 1a: Cohort 1	Dose Escalation: Phase 1a: Cohort 2	Dose Escalation: Phase 1a: Cohort 3	Dose Escalation: Phase 1a: Cohort 4	Dose Escalation: Phase 1a: Cohort 5	Dose Escalation: Phase 1a: Cohort 6	Dose Escalation: Phase 1a: Cohort 7	Dose Escalation: Phase 1a: Cohort 8	Dose Escalation: Phase 1a: Cohort 9	Dose Escalation: Phase 1a: Cohort 10	Dose Escalation: Phase 1a: Cohort 11	Dose Escalation: Phase 1a: Cohort 12	Dose Escalation: Phase 1a: Cohort 13	Dose Escalation: Phase 1a: Cohort 14	Dose Expansion: Phase 1b: Cohort 1	Dose Expansion: Phase 1b: Cohort 2
Total subjects affected by non serious adverse events
subjects affected / exposed	1 / 1 (100.00%)	3 / 3 (100.00%)	4 / 4 (100.00%)	4 / 4 (100.00%)	9 / 9 (100.00%)	8 / 8 (100.00%)	5 / 5 (100.00%)	6 / 6 (100.00%)	7 / 7 (100.00%)	8 / 8 (100.00%)	4 / 4 (100.00%)	9 / 9 (100.00%)	8 / 8 (100.00%)	6 / 6 (100.00%)	12 / 12 (100.00%)	12 / 12 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Tumour pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	1	1	1	0	0	0	0	0	0	0
Deep vein thrombosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0
Hypertension
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Embolism
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Hot flush
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Pallor
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Peripheral embolism
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
General disorders and administration site conditions
Pyrexia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	1	0	0	1	2	0	1	2	0	4	0	0	1	1
Fatigue
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	2 / 4 (50.00%)	2 / 4 (50.00%)	3 / 9 (33.33%)	4 / 8 (50.00%)	1 / 5 (20.00%)	5 / 6 (83.33%)	3 / 7 (42.86%)	5 / 8 (62.50%)	3 / 4 (75.00%)	6 / 9 (66.67%)	4 / 8 (50.00%)	3 / 6 (50.00%)	8 / 12 (66.67%)	7 / 12 (58.33%)
occurrences all number	0	0	4	2	3	10	2	5	6	9	3	11	4	3	12	11
Asthenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	3	0	0	0	1	1	0
Gait disturbance
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Influenza like illness
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	1	0	0	0	1	0	1	1	0	0	0	0	0	1	1
Oedema peripheral
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	2 / 8 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 8 (25.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	1 / 6 (16.67%)	2 / 12 (16.67%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	1	2	0	0	0	2	0	3	0	1	2	2
Chest discomfort
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Chest pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Chills
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	1	1	1	0	0	0	0	1	1
Early satiety
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Infusion site extravasation
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0
Performance status decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Physical deconditioning
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Peripheral swelling
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Immune system disorders
Contrast media reaction
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Reproductive system and breast disorders
Erectile dysfunction
subjects affected / exposed	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 6 (0.00%)	2 / 7 (28.57%)	2 / 8 (25.00%)	1 / 4 (25.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	1 / 6 (16.67%)	3 / 12 (25.00%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	0	1	1	0	2	2	2	2	0	1	4	4
Dyspnoea
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	1 / 4 (25.00%)	2 / 9 (22.22%)	2 / 8 (25.00%)	1 / 6 (16.67%)	2 / 12 (16.67%)	2 / 12 (16.67%)
occurrences all number	0	0	1	1	1	1	1	0	0	2	1	5	2	1	2	2
Oropharyngeal pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	0	0	1	0
Wheezing
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	1
Atelectasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Pleural effusion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	0	0	0
Acute respiratory distress syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1
Pulmonary embolism
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Rhinorrhoea
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Upper respiratory tract congestion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Increased viscosity of upper respiratory secretion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Pneumothorax
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Productive cough
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0
Hallucination, auditory
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Insomnia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	2 / 7 (28.57%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	2	0	0	1	2	0	0	0	0	0	1	1
Anxiety
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	1	1	0
Confusional state
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Irritability
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Product issues
Device breakage
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Investigations
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0	1	0	0	1	0	0	3	0	1	0
Blood creatinine increased
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	2	0	1	1	1	1	0	0	0	0	1	0	0	1	2
Alanine aminotransferase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	4	0	0	0	0	0	0	2	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	6	0	0	0	0	0	0	3	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	1	1	0	0	0	0	0	0	0	0	0	2	0	1	1
Blood cholesterol increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Blood lactate dehydrogenase decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Blood phosphorus decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Electrocardiogram QT interval abnormal
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	3	0	0	0	0	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	1	0	0	0	0	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	2	0	0	0	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	2 / 8 (25.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	2	0	1	0	4	1	0	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	2 / 8 (25.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 6 (16.67%)	2 / 12 (16.67%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	2	0	2	1	2	0	1	1	1	2	0
Weight increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0
White blood cell count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	4	0	0	0	1	0	0	1	0	0	7
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Blood creatinine decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0
Blood sodium decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Eosinophil count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	5	0	0	0	0	0	2
White blood cell count increased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Ejection fraction decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Blood albumin decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Carbon dioxide decreased
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Injury, poisoning and procedural complications
Spinal compression fracture
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Fall
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	1 / 8 (12.50%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	2	2	1	0	0
Stoma prolapse
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Skin laceration
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pelvic fracture
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Procedural pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Rib fracture
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Ulna fracture
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Atrial fibrillation
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Palpitations
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pericardial effusion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Sinus bradycardia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Atrial thrombosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Atrioventricular block first degree
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Tachycardia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	2	1	0	0	0	0	0	0	2	1
Ageusia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Anosmia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Dysgeusia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 6 (0.00%)	4 / 12 (33.33%)	1 / 12 (8.33%)
occurrences all number	0	0	0	1	3	0	0	0	0	0	1	1	1	0	4	1
Headache
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	2 / 8 (25.00%)	0 / 4 (0.00%)	3 / 9 (33.33%)	1 / 8 (12.50%)	1 / 6 (16.67%)	0 / 12 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	2	2	0	1	1	2	0	3	1	1	0	2
Hypoaesthesia
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Sensory loss
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Syncope
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	0	1	1	0	0	0	0	0	0	2
Paraesthesia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Brain oedema
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Neuropathy peripheral
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Post herpetic neuralgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Taste disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Tremor
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Coordination abnormal
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0
Cognitive disorder
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Disturbance in attention
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Parosmia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	1	0	0	1	8	0	0	8	0	3	1	0	0	2
Leukocytosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0	2	0	0	0	0	1	0	0	0	0
Leukopenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1	0	0	0	0	4	0	0	3	1	0	5
Lymphopenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	5	0	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 12 (16.67%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	5
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0
Hyperacusis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Eye disorders
Vision blurred
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Conjunctival haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Eye pain
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vitreous floaters
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Diplopia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	2 / 4 (50.00%)	3 / 4 (75.00%)	7 / 9 (77.78%)	5 / 8 (62.50%)	5 / 5 (100.00%)	5 / 6 (83.33%)	7 / 7 (100.00%)	7 / 8 (87.50%)	4 / 4 (100.00%)	7 / 9 (77.78%)	5 / 8 (62.50%)	4 / 6 (66.67%)	10 / 12 (83.33%)	7 / 12 (58.33%)
occurrences all number	0	1	2	4	16	13	19	8	15	14	5	19	10	8	14	13
Vomiting
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	2 / 4 (50.00%)	5 / 9 (55.56%)	4 / 8 (50.00%)	5 / 5 (100.00%)	3 / 6 (50.00%)	6 / 7 (85.71%)	6 / 8 (75.00%)	1 / 4 (25.00%)	3 / 9 (33.33%)	5 / 8 (62.50%)	3 / 6 (50.00%)	5 / 12 (41.67%)	5 / 12 (41.67%)
occurrences all number	0	0	2	2	10	5	12	5	10	7	2	6	8	5	11	7
Abdominal pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	2 / 8 (25.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	1 / 6 (16.67%)	3 / 12 (25.00%)	1 / 12 (8.33%)
occurrences all number	0	0	1	0	1	2	4	3	1	0	0	1	1	1	3	1
Constipation
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	2 / 5 (40.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	2 / 8 (25.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	3 / 12 (25.00%)
occurrences all number	0	0	0	0	0	1	3	0	0	3	1	0	0	0	1	3
Diarrhoea
subjects affected / exposed	1 / 1 (100.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	4 / 4 (100.00%)	9 / 9 (100.00%)	7 / 8 (87.50%)	2 / 5 (40.00%)	6 / 6 (100.00%)	7 / 7 (100.00%)	6 / 8 (75.00%)	3 / 4 (75.00%)	6 / 9 (66.67%)	7 / 8 (87.50%)	3 / 6 (50.00%)	9 / 12 (75.00%)	6 / 12 (50.00%)
occurrences all number	1	2	1	10	15	17	4	8	11	25	3	11	12	6	22	15
Abdominal distension
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	2	0	0	0	0	1	0	0	0	0
Dry mouth
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	1	0	0	1	0	0	0	0	0	0	1	1	0
Haematochezia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Retching
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	2
Anal incontinence
subjects affected / exposed	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Dyspepsia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	0	0	0	1
Dysphagia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
Faeces soft
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Flatulence
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	1	1	1	1	0	1	0	0	0	0	0	0	1	1
Salivary hypersecretion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	4	0	0	1	0	0	0	2	1
Colitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Food poisoning
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Tooth discolouration
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Ascites
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Parotid gland enlargement
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Rectal haemorrhage
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Tooth erosion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Tooth loss
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Hepatobiliary disorders
Hyperbilirubinaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	2	0	0	1	0	0	0	2	0	0	0	0	1	2
Hepatitis acute
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Biliary dilatation
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Dermatitis acneiform
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	1 / 4 (25.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	1	0	0	1	0
Rash maculo-papular
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Night sweats
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Rash
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	1	0	0	1	0
Rash macular
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Skin lesion
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Hyperhidrosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Renal and urinary disorders
Ketonuria
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Urinary incontinence
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Haematuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Proteinuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Renal colic
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	1 / 4 (25.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Glycosuria
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Endocrine disorders
Pituitary-dependent Cushing's syndrome
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Hypothyroidism
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 8 (12.50%)	1 / 4 (25.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0	1	1	1	1	1	0	1	0	0	0
Myalgia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	1	1	0	0	0	0	0	0	1	0	1
Arthralgia
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	1 / 4 (25.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	1	1	0	0	0	1	0	2	2	0	0	0	0
Groin pain
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Osteoarthritis
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Fistula
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Osteoporosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0
Coccydynia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Infections and infestations
COVID-19
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	1 / 5 (20.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	3 / 9 (33.33%)	0 / 8 (0.00%)	2 / 6 (33.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	1	1	1	0	0	3	0	2	0	0
Pneumonia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 5 (40.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	1	0	1	0	0	0	0
Urinary tract infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	2 / 5 (40.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	3 / 12 (25.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	2	0	1	0	0	0	0	0	4	1
Respiratory tract infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Onychomycosis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	1	0	0
Pneumonia aspiration
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Skin infection
subjects affected / exposed	1 / 1 (100.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	2	0	0	2	0
Candida infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Herpes zoster
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	1 / 6 (16.67%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Vaginal infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	1 / 7 (14.29%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Coronavirus infection
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Influenza
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	1 / 4 (25.00%)	3 / 4 (75.00%)	3 / 9 (33.33%)	3 / 8 (37.50%)	1 / 5 (20.00%)	1 / 6 (16.67%)	2 / 7 (28.57%)	3 / 8 (37.50%)	1 / 4 (25.00%)	2 / 9 (22.22%)	1 / 8 (12.50%)	1 / 6 (16.67%)	6 / 12 (50.00%)	1 / 12 (8.33%)
occurrences all number	0	1	1	3	3	3	1	1	2	6	1	4	2	2	10	1
Hypercalcaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 5 (20.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Dehydration
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	2 / 8 (25.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	4 / 12 (33.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0	0	0	0	5	0
Gout
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	1	0	0	1	0	0	0	0	0	0	2	0	1	0	0
Hyperlipidaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	3 / 9 (33.33%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	3 / 8 (37.50%)	0 / 4 (0.00%)	1 / 9 (11.11%)	2 / 8 (25.00%)	2 / 6 (33.33%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	3	1	0	1	6	3	0	3	2	2	0	0
Hyponatraemia
subjects affected / exposed	0 / 1 (0.00%)	1 / 3 (33.33%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0	3	0	0	0	1
Hypophosphataemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	2 / 9 (22.22%)	1 / 8 (12.50%)	0 / 5 (0.00%)	1 / 6 (16.67%)	1 / 7 (14.29%)	1 / 8 (12.50%)	0 / 4 (0.00%)	4 / 9 (44.44%)	0 / 8 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	2	1	0	1	1	2	0	5	0	0	2	0
Vitamin B12 deficiency
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	1 / 9 (11.11%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Vitamin D deficiency
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Hypoalbuminaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	1 / 8 (12.50%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0
Hypocalcaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 12 (8.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Hypoglycaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	1 / 8 (12.50%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Malnutrition
subjects affected / exposed	0 / 1 (0.00%)	0 / 3 (0.00%)	0 / 4 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 5 (0.00%)	0 / 6 (0.00%)	0 / 7 (0.00%)	0 / 8 (0.00%)	0 / 4 (0.00%)	0 / 9 (0.00%)	0 / 8 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 12 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

01 May 2020

The following changes were made as per Amendment 1: 1. A nonclinical rationale for each new Phase 2 cohort (sarcoma with murine Double minute 2 [MDM2] amplification [Cohort 2], CDKN2A loss [Cohort 3], and molecular features that may confer sensitivity to ASTX295 [Cohort 4]) was provided in addition to the previously defined malignant pleural mesothelioma (MPM) cohort [Cohort 1]. 2. The number of overall subjects and the duration of study was updated based on the additional Phase 2 cohorts. 3. The Phase 2 study design description was updated to define the new cohorts, Cohorts 2-4. 4. Scientific rationale for study design was updated to reflect the new cohorts added for Phase 2. 5. The inclusion and exclusion criteria were updated. 6. In the statistical hypotheses section for Phase 2, hypotheses were included for the new Phase 2 cohorts. 7. The sample size was calculated for new Cohorts 2, 3, and 4.

21 Oct 2020

The following changes were made as per Amendment 2: 1. A secondary objective was added regarding PK parameters of ASTX295 after administration with food. 2. A concomitant change was made regarding the ASTX295 plasma concentration profiles and PK parameters in the fed state. 3. Figure was updated to add a food-effect cohort. 4. The addition of a window to activities occurring beyond Cycle 6. 5. Study rationale section was updated to add the rationale for a food bridging cohort. 6. Background section was updated to include information from a nonclinical PK food-effect study. 7. Objectives and endpoints were updated to include the determination of PK parameters of ASTX295 when administered with food. 8. Overall design section was updated to add the rationale for a food bridging cohort. This section was updated with language to address the impact and changes resulting from the coronavirus disease of 2019 (COVID-19) health emergency. 9. Scientific rational for study design was updated to add the rationale for a food bridging cohort. 10. The "drug administration under fed state" section was added to provide meal requirements and procedures for subjects enrolled into the food-bridging cohort. 11. Study treatments administered section updated to provide information on alternative dispensing of study drug under extenuating circumstances, such as the COVID-19 health emergency. 12. Appendix was added to provide information and guidance to continue study during the COVID-19 emergency.

15 Jun 2021

The following changes were made as per Amendment 3: 1. Allowed an alternate dosing regimen (i.e., BID administration) to enhance exposure and based on the latest research findings. These include BID dosing or administration with food based on results from a food-bridging cohort (Amendment #2). 2. The study numbers were corrected (255 should have read 239) and increased from 28 to 60 for Phase 1a and up to an additional 15 to 20 subjects for Phase 1b. 3. For BID cohorts under fasting conditions, meals and dietary restrictions were updated. 4. Details of alternate dose regimen was updated in drug administration under fed conditions section.

21 Mar 2022

The following changes were made as per Amendment 4: 1. The duration of the study was increased. 2. Intermittent dosing was added to the possible dosing schedule modifications for Phase 1a. 3. The expected total numbers of screened and treated subjects in all phases were increased, and all numbers by phase were specified as approximate. 4. Up to an additional 14 days (up to 35 total screening days) was specified as being allowed for acquisition of archived tissue slides or a fresh biopsy for prospective eligibility confirmation in Phase 2. 5. “Fasting conditions” was deleted from the description of the last safe dose as determined by the DSRC for the description of Amendment 2, Phase 1, Cohort 7. 6. Consideration of twice daily dosing or intermittent dose schedules or meal options for improvement of tolerability while allowing for additional dose escalation was added. 7. The location of Phase 1b was changed from “North America” to “United States; same centers initiated in Phase 1a.” 8. The expected total numbers of screened and treated subjects in all phases were increased, and all numbers by phase were specified as approximate. 9. Inclusion and exclusion criteria were modified.

Were there any global interruptions to the trial? No

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

Phase 2 was not conducted due to Sponsor's strategic decision.

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Clinical trials

Clinical Trial Results: Phase 1/2 Open-Label Study of the Safety, Pharmacokinetics, and Preliminary Activity of ASTX295 in Subjects with Wild-Type TP53 Advanced Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1a and 1b: Number of Subjects with Treatment Emergent Adverse Events (TEAEs), and Serious TEAEs

Primary: Phase 1a and 1b: Number of Subjects with Treatment Emergent Adverse Events (TEAEs), and Serious TEAEs

Primary: Phase 1a: Number of Subjects with Dose-limiting Toxicities (DLTs)

Primary: Phase 1a: Number of Subjects with Dose-limiting Toxicities (DLTs)

Secondary: Phase 1a and 1b: Disease Control Rate (DCR)

Secondary: Phase 1a and 1b: Disease Control Rate (DCR)

Secondary: Phase 1a and 1b: Objective Response Rate (ORR)

Secondary: Phase 1a and 1b: Objective Response Rate (ORR)

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of ASTX295

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to Time of Last Measurable Concentration (AUClast) of ASTX295

Secondary: Phase 1a and 1b: Maximum Observed Plasma Concentration (Cmax) of ASTX295

Secondary: Phase 1a and 1b: Maximum Observed Plasma Concentration (Cmax) of ASTX295

Secondary: Phase 1a and 1b: Minimum Observed Plasma Concentration (Cmin) of ASTX295

Secondary: Phase 1a and 1b: Minimum Observed Plasma Concentration (Cmin) of ASTX295

Secondary: Phase 1a and 1b: Time to Maximum Observed Plasma Concentration (Tmax) of ASTX295

Secondary: Phase 1a and 1b: Time to Maximum Observed Plasma Concentration (Tmax) of ASTX295

Secondary: Phase 1a and 1b: Elimination Half-life (t1/2) of ASTX295

Secondary: Phase 1a and 1b: Elimination Half-life (t1/2) of ASTX295

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX295

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX295

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of ASTX295

Secondary: Phase 1a and 1b: Area Under the Concentration-time Curve From Time Zero to Infinity (AUC0-inf) of ASTX295

Secondary: Phase 1a: AUC0-24 of ASTX295 Under Fed State

Secondary: Phase 1a: AUC0-24 of ASTX295 Under Fed State

Secondary: Phase 1a: AUClast of ASTX295 Under Fed State

Secondary: Phase 1a: AUClast of ASTX295 Under Fed State

Secondary: Phase 1a: AUC0-inf of ASTX295 Under Fed State

Secondary: Phase 1a: AUC0-inf of ASTX295 Under Fed State

Secondary: Phase 1a: Cmax of ASTX295 Under Fed State

Secondary: Phase 1a: Cmax of ASTX295 Under Fed State

Secondary: Phase 1a: Cmin of ASTX295 Under Fed State

Secondary: Phase 1a: Cmin of ASTX295 Under Fed State

Secondary: Phase 1a: Tmax of ASTX295 Under Fed State

Secondary: Phase 1a: Tmax of ASTX295 Under Fed State

Secondary: Phase 1a: The t1/2 of ASTX295 Under Fed State

Secondary: Phase 1a: The t1/2 of ASTX295 Under Fed State

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
Phase 1/2 Open-Label Study of the Safety, Pharmacokinetics, and Preliminary Activity of ASTX295 in Subjects with Wild-Type TP53 Advanced Solid Tumors