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Clinical Trial Results:
A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects with Advanced Solid Tumors

Summary
EudraCT number	2018-004568-72
Trial protocol	FR ES
Global end of trial date	03 Mar 2025

Results information
Results version number	v1(current)
This version publication date	02 Jul 2025
First version publication date	02 Jul 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

ASTX029-01

ISRCTN number

US NCT number

NCT03520075

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

03 Mar 2025

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Mar 2025

Was the trial ended prematurely?

Main objective of the trial

The main objective of this study was to assess safety and to identify the maximum tolerated dose (MTD), the recommended Phase 2 (RP2D), and the recommended dosing regimen of ASTX029 in Phase 1 Part A (Dose Escalation) and Part B (Dose Expansion) and to assess preliminary clinical activity, as determined by ORR in tumors characterized by gene aberrations in the MAPK signal pathway that may confer sensitivity to ASTX029 in Phase 2.

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

07 May 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Spain: 16

Country: Number of subjects enrolled

France: 18

Country: Number of subjects enrolled

United Kingdom: 15

Country: Number of subjects enrolled

United States: 141

Worldwide total number of subjects

190

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 took part at regional sites in United States (US), France, Spain, and United Kingdom (UK) from 07 May 2018 to 03 March 2025.

Screening details

A total of 192 subjects were enrolled in the study to receive ASTX029, of which 2 subjects died before receiving treatment. The study consisted of 2 phases: Phase 1: Cohorts 1-12 in Part A (Dose Escalation) and a single cohort for Part B (Dose Expansion) and Phase 2: Cohorts A to F.

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

Phase 1A: Cohort 1 Dose Escalation

Arm description

Subjects received ASTX029 10 milligrams (mg), powder in bottle (PiB), orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and effervescent powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 10 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Phase 1A: Cohort 2 Dose Escalation

Arm description

Subjects received ASTX029 20 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and effervescent powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 20 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Phase 1A: Cohort 3 Dose Escalation

Arm description

Subjects received ASTX029 60 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and effervescent powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 60 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Phase 1A: Cohort 4 Dose Escalation

Arm description

Subjects received ASTX029 120 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and effervescent powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 120 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Phase 1A: Cohort 5 Dose Escalation

Arm description

Subjects received ASTX029 200 mg, orally, PiB, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Powder and effervescent powder for oral suspension

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Phase 1A: Cohort 6 Dose Escalation

Arm description

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Phase 1A: Cohort 7 Dose Escalation

Arm description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Phase 1A: Cohort 8 Dose Escalation

Arm description

Subjects received ASTX029 40 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 40 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Phase 1A: Cohort 9 Dose Escalation

Arm description

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Phase 1A: Cohort 10 Dose Escalation

Arm description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Phase 1A: Cohort 11 Dose Escalation

Arm description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Phase 1A: Cohort 12 Dose Escalation

Arm description

Subjects received ASTX029 280 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 280 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Phase 1B Dose Expansion

Arm description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Phase 2: Cohort A

Arm description

Subjects with neuroblastoma RAS (NRAS)-mutant melanoma received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Phase 2: Cohort B

Arm description

Subjects with Kirsten RAS (KRAS)-mutant or KRAS-amplified non-small cell lung cancer (NSCLC) received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Phase 2: Cohort C

Arm description

Subjects with B isoform of RAF kinase (BRAF) V600-mutant cancers (non-colorectal cancers) received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Phase 2: Cohort D

Arm description

Subjects with BRAF-fusion cancers received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Phase 2: Cohort E

Arm description

Subjects with gynecological cancers with alterations in the mitogen-activated protein kinase (MAPK) pathway received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Phase 2: Cohort F

Arm description

Subjects with tumors that were characterized by other gene aberrations (that upregulate the MAPK signal pathway) received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Arm type

Experimental

Investigational medicinal product name

ASTX029

Investigational medicinal product code

Other name

Pharmaceutical forms

Tablet

Routes of administration

Oral use

Dosage and administration details

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Number of subjects in period 1	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 1B Dose Expansion	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Started	3	3	3	5	10	6	3	3	3	3	7	7	20	32	15	12	9	32	14
Completed	0	0	0	0	0	0	0	0	0	0	1	0	1	6	0	0	0	5	0
Not completed	3	3	3	5	10	6	3	3	3	3	6	7	19	26	15	12	9	27	14
Death	2	2	3	2	6	4	3	2	3	1	5	7	11	20	13	9	5	14	11
Lost to Follow-up	-	1	-	1	1	-	-	-	-	-	1	-	1	-	1	1	-	-	1
Complete Consent Withdrawal	1	-	-	2	3	2	-	1	-	1	-	-	4	-	1	2	1	3	2
Study Terminated by Sponsor	-	-	-	-	-	-	-	-	-	1	-	-	3	6	-	-	3	10	-

Baseline characteristics

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Reporting group title

Phase 1A: Cohort 1 Dose Escalation

Reporting group description

Subjects received ASTX029 10 milligrams (mg), powder in bottle (PiB), orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 2 Dose Escalation

Reporting group description

Subjects received ASTX029 20 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 3 Dose Escalation

Reporting group description

Subjects received ASTX029 60 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 4 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 5 Dose Escalation

Reporting group description

Subjects received ASTX029 200 mg, orally, PiB, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 6 Dose Escalation

Reporting group description

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 7 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 8 Dose Escalation

Reporting group description

Subjects received ASTX029 40 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 9 Dose Escalation

Reporting group description

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 10 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 11 Dose Escalation

Reporting group description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 12 Dose Escalation

Reporting group description

Subjects received ASTX029 280 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1B Dose Expansion

Reporting group description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 2: Cohort A

Reporting group description

Subjects with neuroblastoma RAS (NRAS)-mutant melanoma received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Reporting group title

Phase 2: Cohort B

Reporting group description

Reporting group title

Phase 2: Cohort C

Reporting group description

Reporting group title

Phase 2: Cohort D

Reporting group description

Subjects with BRAF-fusion cancers received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Reporting group title

Phase 2: Cohort E

Reporting group description

Reporting group title

Phase 2: Cohort F

Reporting group description

Reporting group values	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 1B Dose Expansion	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F	Total
Number of subjects	3	3	3	5	10	6	3	3	3	3	7	7	20	32	15	12	9	32	14	190
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
Units: years
arithmetic mean (standard deviation)	69.3 ( 2.52 )	57.7 ( 9.50 )	56.7 ( 10.12 )	57.6 ( 5.22 )	62.8 ( 8.82 )	61.0 ( 6.72 )	49.7 ( 9.71 )	66.3 ( 9.07 )	63.3 ( 8.50 )	61.7 ( 3.51 )	60.7 ( 9.30 )	61.7 ( 14.95 )	60.3 ( 15.63 )	65.3 ( 9.92 )	66.8 ( 10.90 )	56.7 ( 16.14 )	66.2 ( 4.60 )	63.7 ( 9.26 )	65.6 ( 10.55 )	-
Gender categorical
Units: Subjects
Female	3	2	2	5	6	3	3	3	3	1	2	4	12	12	10	7	5	32	6	121
Male	0	1	1	0	4	3	0	0	0	2	5	3	8	20	5	5	4	0	8	69
Ethnicity
Units: Subjects
Not of Hispanic, Latino/a, or Spanish origin	2	3	3	5	10	5	2	3	1	3	7	6	19	30	12	8	8	25	12	164
Missing	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	3	0	4
Hispanic, Latino/a, or Spanish origin	1	0	0	0	0	1	1	0	2	0	0	1	1	2	3	3	1	4	2	22
Race
Units: Subjects
Asian	0	0	0	1	0	0	0	0	0	0	0	2	1	0	0	0	1	0	1	6
American Indian or Alaskan Native	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Black or African American	0	2	0	0	1	0	1	0	0	1	0	0	2	0	1	0	0	0	0	8
Native Hawaiian and Pacific Islander	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
White	3	1	3	4	9	6	1	3	3	2	6	5	16	20	12	7	6	27	11	145
Other	0	0	0	0	0	0	1	0	0	0	1	0	1	0	1	0	0	0	0	4
Not reported	0	0	0	0	0	0	0	0	0	0	0	0	0	10	0	4	2	4	1	21
Multiple	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Unknown	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1	0	1	1	5

End points

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Reporting group title

Phase 1A: Cohort 1 Dose Escalation

Reporting group description

Subjects received ASTX029 10 milligrams (mg), powder in bottle (PiB), orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 2 Dose Escalation

Reporting group description

Subjects received ASTX029 20 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 3 Dose Escalation

Reporting group description

Subjects received ASTX029 60 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 4 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 5 Dose Escalation

Reporting group description

Subjects received ASTX029 200 mg, orally, PiB, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 6 Dose Escalation

Reporting group description

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 7 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 8 Dose Escalation

Reporting group description

Subjects received ASTX029 40 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 9 Dose Escalation

Reporting group description

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 10 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 11 Dose Escalation

Reporting group description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 12 Dose Escalation

Reporting group description

Subjects received ASTX029 280 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1B Dose Expansion

Reporting group description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 2: Cohort A

Reporting group description

Subjects with neuroblastoma RAS (NRAS)-mutant melanoma received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Reporting group title

Phase 2: Cohort B

Reporting group description

Reporting group title

Phase 2: Cohort C

Reporting group description

Reporting group title

Phase 2: Cohort D

Reporting group description

Subjects with BRAF-fusion cancers received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Reporting group title

Phase 2: Cohort E

Reporting group description

Reporting group title

Phase 2: Cohort F

Reporting group description

Subject analysis set title

Phase 1A: Cohort 10 Dose Escalation

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Subject analysis set title

Phase 1A: Cohort 11 Dose Escalation

Subject analysis set type

Full analysis

Subject analysis set description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Primary: Phase 1: Number of Subjects With Dose Limiting Toxicities (DLTs)

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End point title

Phase 1: Number of Subjects With Dose Limiting Toxicities (DLTs) ^[1] ^[2]

End point description

DLTs were defined as adverse events (AEs) graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria that occurred during the first cycle of treatment and represented any 1 of the following: grade 4 thrombocytopenia of any duration; ≥grade 3 hematologic toxicity with complications (e.g., grade 3 thrombocytopenia with bleeding or transfusion requirement); febrile neutropenia of any duration or grade 4 neutropenia of 5 days or more duration; liver-associated abnormalities; ≥grade 2 eye disorders; symptomatic grade 2 cutaneous toxicities (including skin rash); any other ≥grade 3 nonhematologic AE except grade 3 nausea, vomiting, or diarrhea; Any event that, in the opinion of the Data and Safety Review Committee (DSRC), would suggest that further dose escalation would put subjects at unacceptable risk. The safety analysis set included data from all subjects who received any amount of study drug.

End point type

Primary

End point timeframe

Cycle 1 (cycle length = 21 days)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics is provided for this end point.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data is reported only for the treatment arm groups applicable for this end point.

End point values	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 1B Dose Expansion
Number of subjects analysed	3	3	3	5	10	6	3	3	3	3	7	7	20
Units: count of subjects	0	0	0	0	1	0	0	0	0	0	0	1	0

No statistical analyses for this end point

Primary: Phase 1: Number of Subjects with Treatment Emergent Adverse Events (TEAEs)

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End point title

Phase 1: Number of Subjects with Treatment Emergent Adverse Events (TEAEs) ^[3] ^[4]

End point description

An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. TEAEs are defined as events that first occurred or worsened on or after the date of the first dose of study treatment until 30 days after the last dose of study treatment or until the start of a posttreatment alternative anti-cancer treatment, whichever occurs first, with the following exceptions: events that occurred after 30 days beyond the last dose of study treatment or the start of a posttreatment alternative anti-cancer treatment will also be considered treatment-emergent if the events are both serious and related to the study treatment. The safety analysis set included data from all subjects who received any amount of study drug.

End point type

Primary

End point timeframe

From first dose of study drug up to 30 days after last dose (Up to 74 months)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics is provided for this end point.
[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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	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 1B Dose Expansion
Number of subjects analysed	3	3	3	5	10	6	3	3	3	3	7	7	20
Units: count of subjects	3	3	3	5	10	6	3	3	3	3	7	7	20

No statistical analyses for this end point

Primary: Phase 2: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

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End point title

Phase 2: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 ^[5] ^[6]

End point description

The ORR was calculated as the number of evaluable subjects whose best response was complete response (CR) or partial response (PR), divided by the total number of subjects evaluable for ORR analysis. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 millimeters (mm). PR was defined as at least a 30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Percentages were rounded off to the nearest single decimal place. The efficacy analysis set included all subjects who received any amount of study drug. The ORR analysis was based on subjects who were in the efficacy analysis set and 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

Primary

End point timeframe

Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 74 months)

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistics is provided for this end point.
[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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	32	15	12	9	32	14
Units: percentage of subjects
number (confidence interval 90%)	12.5 (4.4 to 26.4)	0 (0 to 18.1)	8.3 (0.4 to 33.9)	0 (0 to 28.3)	12.5 (4.4 to 26.4)	7.1 (0.4 to 29.7)

No statistical analyses for this end point

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX029

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End point title

Phase 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX029 ^[7]

End point description

As per planned analysis, data for subjects from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). The pharmacokinetics (PK) analysis set included all subjects who had received study drug with available plasma concentrations and PK parameters for ASTX029. Here, subjects analysed is the number of subjects with data available for analysis and 'n' represents unique number of subjects out of all the assessed subjects with data available at the specified timepoint. 2 subjects who received 200 and 280 mg respectively, in Cycle 1 Day1 (C1D1), received 120 mg in Cycle 2 and Day 1 (C2D1) and hence counted in Cohort 10. 1 subject who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	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 12 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation	Phase 1A: Cohort 11 Dose Escalation
Number of subjects analysed	3	3	3	5	10	6	3	2	3	7	5	26
Units: hoursnanograms/millilitres (hng/mL)
geometric mean (geometric coefficient of variation)
C1D1 (n = 2,3,3,5,10,6,3,2,3,3,26,7)	277 ( 20.1 )	361 ( 222.0 )	1150 ( 10.0 )	4020 ( 83.0 )	7250 ( 63.7 )	1810 ( 126.9 )	3360 ( 140.4 )	3080 ( 128.2 )	6500 ( 64.3 )	17800 ( 83.6 )	5710 ( 27.1 )	13400 ( 46.4 )
C2D1 (n = 3,2,3,4,5,4,3,2,3,5,23,3)	339 ( 58.4 )	618 ( 11.7 )	1410 ( 61.4 )	3530 ( 104.5 )	7550 ( 76.9 )	2490 ( 108.4 )	3710 ( 106.0 )	3370 ( 117.8 )	6430 ( 71.6 )	25600 ( 91.9 )	7850 ( 37.1 )	15400 ( 57.5 )

No statistical analyses for this end point

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ASTX029

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End point title

Phase 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ASTX029 ^[8]

End point description

As per planned analysis, data for subjects from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). The PK analysis set included all subjects who had received study drug with available plasma concentrations and PK parameters for ASTX029. Here, subjects analysed is the number of subjects with data available for analysis and 'n' represents unique number of subjects out of all the assessed subjects with data available at the specified timepoint. 2 subjects who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 subject who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	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 12 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation	Phase 1A: Cohort 11 Dose Escalation
Number of subjects analysed	3	3	3	5	10	6	3	3	3	7	5	27
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n = 3,3,3,5,10,6,3,3,3,3,27,7)	262 ( 18.5 )	347 ( 215.6 )	1140 ( 10.0 )	4020 ( 82.9 )	7250 ( 63.7 )	1740 ( 137.5 )	3360 ( 140.4 )	1620 ( 215.6 )	6450 ( 65.8 )	17800 ( 83.6 )	5710 ( 26.9 )	12800 ( 51.2 )
C2D1 (n = 3,3,3,4,5,4,3,2,3,5,25,3)	321 ( 56.1 )	298 ( 177.3 )	1410 ( 61.5 )	3530 ( 104.5 )	7530 ( 77.2 )	2430 ( 116.3 )	3660 ( 104.2 )	3340 ( 116.4 )	6450 ( 72.0 )	25300 ( 93.7 )	7850 ( 37.1 )	13500 ( 80.0 )

No statistical analyses for this end point

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of ASTX029

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End point title

Phase 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of ASTX029 ^[9]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

Notes
[9] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data is reported only for the treatment arm groups applicable for this end point.

End point values	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 12 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation	Phase 1A: Cohort 11 Dose Escalation
Number of subjects analysed	3	3	3	5	9	4	3	2	3	7	5	25
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n= 2,3,2,5,9,4,3,2,3,3,25,7)	327 ( 3.6 )	358 ( 209.2 )	1150 ( 14.1 )	4050 ( 82.5 )	8170 ( 53.5 )	1180 ( 112.9 )	3390 ( 139.3 )	3120 ( 126.3 )	6520 ( 66.6 )	17900 ( 83.1 )	5770 ( 26.7 )	13500 ( 47.1 )
C2D1 (n= 3,2,3,3,5,4,2,2,2,5,25,3)	346 ( 52.9 )	243 ( 228.9 )	1430 ( 60.9 )	5160 ( 55.0 )	7670 ( 75.3 )	2470 ( 116.1 )	3190 ( 169.8 )	3420 ( 113.6 )	5590 ( 101.3 )	25600 ( 92.2 )	7930 ( 37.2 )	15700 ( 59.0 )

No statistical analyses for this end point

Secondary: Phase 1: Maximum Observed Plasma Concentration (Cmax) of ASTX029

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End point title

Phase 1: Maximum Observed Plasma Concentration (Cmax) of ASTX029 ^[10]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	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 12 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation	Phase 1A: Cohort 11 Dose Escalation
Number of subjects analysed	3	3	3	5	10	6	3	3	3	7	5	27
Units: nanograms/millilitre (ng/mL)
geometric mean (geometric coefficient of variation)
C1D1 (n= 3,3,3,5,10,6,3,3,3,5,27,7)	109 ( 48.5 )	217 ( 165.4 )	469 ( 9.5 )	1650 ( 56.8 )	1850 ( 66.7 )	496 ( 127.7 )	1490 ( 141.7 )	742 ( 301.5 )	2840 ( 30.8 )	6040 ( 58.4 )	2060 ( 49.5 )	5240 ( 61.0 )
C2D1 (n= 3,3,3,4,5,4,3,2,3,5,25,3)	143 ( 177.8 )	107 ( 119.2 )	598 ( 111.0 )	903 ( 228.8 )	1830 ( 177.6 )	641 ( 91.4 )	1710 ( 124.4 )	2330 ( 130.8 )	1860 ( 55.8 )	8070 ( 50.7 )	2360 ( 40.9 )	5350 ( 78.7 )

No statistical analyses for this end point

Secondary: Phase 1: Minimum Plasma Concentration (Cmin) of ASTX029

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End point title

Phase 1: Minimum Plasma Concentration (Cmin) of ASTX029 ^[11]

End point description

As per planned analysis, data for subjects from Part A (Dose Escalation) and Part B (Expansion) were combined for Cohort 11 (200 mg). The PK analysis set included all subjects who had received study drug with available plasma concentrations and PK parameters for ASTX029. Here, subjects analysed is the number of subjects with data available for analysis. 2 subjects who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10. 1 subject who received 280 mg in C1D1, received 200 mg in C2D1 and hence counted in Cohort 11. Data for Cmin was calculated and analysed for C2D1 only.

End point type

Secondary

End point timeframe

Pre-dose and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycle 2 (Cycle length = 21 days)

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data is reported only for the treatment arm groups applicable for this end point.

End point values	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 12 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation	Phase 1A: Cohort 11 Dose Escalation
Number of subjects analysed	3	3	3	4	5	4	3	2	3	3	5	25
Units: ng/mL
geometric mean (geometric coefficient of variation)	4.38 ( 86.7 )	1.45 ( 173.2 )	23.4 ( 127.8 )	19.3 ( 149.7 )	18.1 ( 39.7 )	7.88 ( 79.3 )	68.1 ( 128.8 )	8.68 ( 64.0 )	20.1 ( 114.7 )	168 ( 85.6 )	85.3 ( 206.9 )	188 ( 194.3 )

No statistical analyses for this end point

Secondary: Phase 1: Time to Reach Maximum Concentration (Tmax) of ASTX029

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End point title

Phase 1: Time to Reach Maximum Concentration (Tmax) of ASTX029 ^[12]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data is reported only for the treatment arm groups applicable for this end point.

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 12 Dose Escalation

Phase 1A: Cohort 10 Dose Escalation

Phase 1A: Cohort 11 Dose Escalation

Number of subjects analysed

Units: hours

median (full range (min-max))

C1D1 (n= 3,3,3,5,10,6,3,3,3,3,27,7)

1.08 (0.57 to 3.05)

0.50 (0.50 to 0.58)

0.55 (0.47 to 0.97)

0.50 (0.50 to 1.00)

0.71 (0.43 to 4.08)

3.03 (1.08 to 5.73)

1.00 (0.98 to 3.00)

1.07 (1.00 to 4.02)

1.00 (0.47 to 1.88)

2.03 (1.00 to 4.00)

1.88 (0.53 to 1.93)

1.97 (0.50 to 6.00)

C2D1 (n= 3,3,3,4,5,4,3,2,3,5,25,3)

0.53 (0.50 to 2.20)

1.00 (0.55 to 1.05)

0.50 (0.47 to 0.92)

2.52 (0.92 to 5.7)

0.55 (0.50 to 1.00)

2.48 (0.52 to 3.85)

1.02 (0.50 to 7.53)

1.52 (1.00 to 2.03)

3.00 (2.93 to 5.67)

1.90 (0.55 to 3.85)

2.1 (1.08 to 4)

2.02 (0.92 to 7.52)

No statistical analyses for this end point

Secondary: Phase 1: Elimination Half-Life (T1/2) of ASTX029

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End point title

Phase 1: Elimination Half-Life (T1/2) of ASTX029 ^[13]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

Notes
[13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The data is reported only for the treatment arm groups applicable for this end point.

End point values	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 12 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation	Phase 1A: Cohort 11 Dose Escalation
Number of subjects analysed	3	3	3	5	9	4	3	2	3	7	5	25
Units: hours
geometric mean (geometric coefficient of variation)
C1D1 (n= 2,3,2,5,9,4,3,2,3,3,25,7)	2.42 ( 42.1 )	1.63 ( 18.7 )	4.42 ( 1.8 )	3.75 ( 26.9 )	3.84 ( 21.8 )	2.08 ( 102.4 )	4.28 ( 11.6 )	5.68 ( 31.7 )	3.30 ( 74.7 )	3.71 ( 32.9 )	4.00 ( 13.6 )	3.92 ( 40.9 )
C2D1 (n= 3,2,3,3,5,4,2,2,2,5,21,3)	3.37 ( 119.7 )	1.85 ( 64.8 )	4.98 ( 31.5 )	3.61 ( 13.5 )	4.11 ( 15.9 )	2.58 ( 95.1 )	1.01 ( 11.6 )	3.13 ( 276.4 )	4.67 ( 24.1 )	1.28 ( 72.1 )	3.88 ( 25.6 )	3.80 ( 47.2 )

No statistical analyses for this end point

Secondary: Phase 1: Effect of Food on AUC0-24 of ASTX029

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End point title

Phase 1: Effect of Food on AUC0-24 of ASTX029 ^[14]

End point description

The food effect was to be analysed only for tablet dosage forms. The subjects who were administered 80 mg and 120 mg tablets, under both fed and fasted conditions were reported. As 200 mg dose was administered, as tablets, only under fasted conditions, hence food effect was not assessed for 200 mg dose. The statistical comparison between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this end point for food effect. The data is reported here for the arm groups of 80 mg and 120 mg, in both fed and fasted to compare food effect. Here, subjects analysed is the number of subjects with data available for analysis and 'n' represents unique number of subjects out of all the assessed subjects with data available at the specified timepoint. The 2 subjects who received 200 and 280 mg respectively, in C1D1, received 120 mg in C2D1 and hence counted in Cohort 10.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The statistical analysis was planned only between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this end point or food effect for this endpoint.

End point values	Phase 1A: Cohort 6 Dose Escalation	Phase 1A: Cohort 7 Dose Escalation	Phase 1A: Cohort 9 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation
Number of subjects analysed	6	3	3	5
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n= 6,3,3,3)	1810 ( 126.9 )	3360 ( 140.4 )	6500 ( 64.3 )	5710 ( 27.1 )
C2D1 (n= 4.3.3.5)	2490 ( 108.4 )	3710 ( 106.0 )	6430 ( 71.6 )	7850 ( 37.1 )

Comparison of Cohorts 6 and 9 (80 mg) in C1D1

Statistical analysis description

Comparison of effect of food on AUC0-24 between Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 6 Dose Escalation v Phase 1A: Cohort 9 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[15]

Method

Parameter type

Geo LSM Ratio

Point estimate

27.8

Confidence interval

level

90%

sides

2-sided

lower limit

8.5

upper limit

91.2

Notes
[15] - Geometric Leat Squares Mean Ratio (Geo LSM Ratio) was calculated for Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029.

Comparison of Cohorts 6 and 9 (80 mg) in C2D1

Statistical analysis description

Comparison of effect of food on AUC0-24 between Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029 in C2D1.

Comparison groups

Phase 1A: Cohort 6 Dose Escalation v Phase 1A: Cohort 9 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[16]

Method

Parameter type

Geo LSM Ratio

Point estimate

38.8

Confidence interval

level

90%

sides

2-sided

lower limit

11.4

upper limit

132

Notes
[16] - Geo LSM ratio was calculated for Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029.

Comparison of Cohorts 7 and 10 (120 mg) in C1D1

Statistical analysis description

Comparison of effect of food on AUC0-24 between Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 7 Dose Escalation v Phase 1A: Cohort 10 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[17]

Method

Parameter type

Geo LSM Ratio

Point estimate

58.9

Confidence interval

level

90%

sides

2-sided

lower limit

15.7

upper limit

222

Notes
[17] - Geo LSM ratio was calculated for Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029.

Comparison of Cohorts 7 and 10 (120 mg) in C2D1

Statistical analysis description

Comparison of effect of food on AUC0-24 between Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029 in C2D1.

Comparison groups

Phase 1A: Cohort 7 Dose Escalation v Phase 1A: Cohort 10 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[18]

Method

Parameter type

Geo LSM Ratio

Point estimate

47.2

Confidence interval

level

90%

sides

2-sided

lower limit

20.7

upper limit

108

Notes
[18] - Geo LSM ratio was calculated for Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029.

Secondary: Phase 1: Effect of Food on AUC0-inf of ASTX029

Top of page

End point title

Phase 1: Effect of Food on AUC0-inf of ASTX029 ^[19]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: The statistical analysis was planned only between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this end point for food effect for this endpoint.

End point values	Phase 1A: Cohort 6 Dose Escalation	Phase 1A: Cohort 7 Dose Escalation	Phase 1A: Cohort 9 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation
Number of subjects analysed	4	3	3	5
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n= 4,3,3,3)	1180 ( 112.9 )	3390 ( 139.3 )	6520 ( 66.6 )	5770 ( 26.7 )
C2D1 (n= 4,2,2,5)	2470 ( 116.1 )	3190 ( 169.8 )	5590 ( 101.3 )	7930 ( 37.2 )

Comparison of Cohorts 6 and 9 (80 mg) in C1D1

Statistical analysis description

Comparison of effect of food on AUC0-inf between Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 6 Dose Escalation v Phase 1A: Cohort 9 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[20]

Method

Parameter type

Geo LSM Ratio

Point estimate

18.1

Confidence interval

level

90%

sides

2-sided

lower limit

5.28

upper limit

61.9

Notes
[20] - Geo LSM ratio was calculated for Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029.

Comparison of Cohorts 6 and 9 (80 mg) in C2D1

Statistical analysis description

Comparison of effect of food on AUC0-inf between Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029 in C2D1.

Comparison groups

Phase 1A: Cohort 6 Dose Escalation v Phase 1A: Cohort 9 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[21]

Method

Parameter type

Geo LSM Ratio

Point estimate

44.1

Confidence interval

level

90%

sides

2-sided

lower limit

8.32

upper limit

234

Notes
[21] - Geo LSM ratio was calculated for Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029.

Comparison of Cohort 7 and 10 (120 mg) in C1D1

Statistical analysis description

Comparison of effect of food on AUC0-inf between Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 7 Dose Escalation v Phase 1A: Cohort 10 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[22]

Method

Parameter type

Geo LSM Ratio

Point estimate

58.7

Confidence interval

level

90%

sides

2-sided

lower limit

15.7

upper limit

220

Notes
[22] - Geo LSM ratio was calculated for Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029.

Comparison of Cohorts 7 and 10 (120 mg) in C2D1

Statistical analysis description

Comparison of effect of food on AUC0-inf between Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029 in C2D1.

Comparison groups

Phase 1A: Cohort 7 Dose Escalation v Phase 1A: Cohort 10 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[23]

Method

Parameter type

Geo LSM Ratio

Point estimate

40.2

Confidence interval

level

90%

sides

2-sided

lower limit

14.3

upper limit

113

Notes
[23] - Geo LSM ratio was calculated for Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029.

Secondary: Phase 1: Effect of Food on Cmax of ASTX029

Top of page

End point title

Phase 1: Effect of Food on Cmax of ASTX029 ^[24]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

Notes
[24] - 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: The statistical analysis was planned only between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this end point for food effect for this endpoint.

End point values	Phase 1A: Cohort 6 Dose Escalation	Phase 1A: Cohort 7 Dose Escalation	Phase 1A: Cohort 9 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation
Number of subjects analysed	6	3	3	5
Units: ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n= 6,3,3,3)	496 ( 127.7 )	1490 ( 141.7 )	2840 ( 30.8 )	2060 ( 49.5 )
C2D1 (n= 4,3,3,5)	641 ( 91.4 )	1710 ( 124.4 )	1860 ( 55.8 )	2360 ( 40.9 )

Comparison of Cohorts 6 and 9 (80 mg) in C1D1

Statistical analysis description

Comparison of effect of food on Cmax between Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 6 Dose Escalation v Phase 1A: Cohort 9 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[25]

Method

Parameter type

Geo LSM Ratio

Point estimate

17.5

Confidence interval

level

90%

sides

2-sided

lower limit

5.62

upper limit

54.3

Notes
[25] - Geo LSM ratio was calculated for Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029.

Comparison of Cohorts 6 and 9 (80 mg) in C2D1

Statistical analysis description

Comparison of effect of food on Cmax between Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029 in C2D1.

Comparison groups

Phase 1A: Cohort 6 Dose Escalation v Phase 1A: Cohort 9 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[26]

Method

Parameter type

Geo LSM Ratio

Point estimate

34.5

Confidence interval

level

90%

sides

2-sided

lower limit

upper limit

99.4

Notes
[26] - Geo LSM ratio was calculated for Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029.

Comparison of Cohorts 7 and 10 (120 mg) in C1D1

Statistical analysis description

Comparison of effect of food on Cmax between Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 7 Dose Escalation v Phase 1A: Cohort 10 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[27]

Method

Parameter type

Geo LSM Ratio

Point estimate

72.6

Confidence interval

level

90%

sides

2-sided

lower limit

17.6

upper limit

299

Notes
[27] - Geo LSM ratio was calculated for Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029.

Comparison of Cohorts 7 and 10 (120 mg) in C2D1

Statistical analysis description

Comparison of effect of food on Cmax between Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029 in C2D1.

Comparison groups

Phase 1A: Cohort 7 Dose Escalation v Phase 1A: Cohort 10 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[28]

Method

Parameter type

Geo LSM Ratio

Point estimate

72.5

Confidence interval

level

90%

sides

2-sided

lower limit

29.1

upper limit

181

Notes
[28] - Geo LSM ratio was calculated for Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029.

Secondary: Phase 1: Effect of Food on Tmax of ASTX029

Top of page

End point title

Phase 1: Effect of Food on Tmax of ASTX029 ^[29]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1 and 2 and at 0.5, 1, 2, 3, 4, 6, and 8 hours post-dose on Day 1 of Cycles 1 and 2 (Cycle length = 21 days)

Notes
[29] - 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: The statistical analysis was planned only between fed and fasted state treatment arm groups of 80 mg and 120 mg doses is reported in this end point for food effect for this endpoint.

End point values	Phase 1A: Cohort 6 Dose Escalation	Phase 1A: Cohort 7 Dose Escalation	Phase 1A: Cohort 9 Dose Escalation	Phase 1A: Cohort 10 Dose Escalation
Number of subjects analysed	6	3	3	5
Units: hours
median (full range (min-max))
C1D1 (n= 6,3,3,3)	3.03 (1.08 to 5.73)	1.00 (0.98 to 3.00)	1.00 (0.47 to 1.88)	1.88 (0.53 to 1.93)
C2D1 (n= 4,3,3,5)	2.48 (0.52 to 3.85)	1.02 (0.50 to 7.53)	3.00 (2.93 to 5.67)	2.1 (1.08 to 4)

Comparison of Cohorts 6 and 9 (80 mg) in C1D1

Statistical analysis description

Comparison of effect of food on Tmax between Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 9 Dose Escalation v Phase 1A: Cohort 6 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[30]

P-value

= 0.038867

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges-Lehmann Estimator

Point estimate

-2.275

Confidence interval

level

90%

sides

2-sided

lower limit

-5.216

upper limit

0.083

Notes
[30] - The Hodges-Lehmann estimator and 90% confidence interval (CI) was calculated using the Moses approximation.

Comparison of Cohorts 6 and 9 (80 mg) in C2D1

Statistical analysis description

Comparison of effect of food on Tmax between Cohort 6 (fed state) and Cohort 9 (fasted state) treatment arm groups of 80 mg ASTX029 in C2D1.

Comparison groups

Phase 1A: Cohort 6 Dose Escalation v Phase 1A: Cohort 9 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[31]

P-value

= 0.4795

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges-Lehmann Estimator

Point estimate

1.45

Confidence interval

level

90%

sides

2-sided

lower limit

-0.917

upper limit

5.15

Notes
[31] - The Hodges-Lehmann estimator and 90% CI was calculated using the Moses approximation.

Comparison of Cohorts 7 and 10 (120 mg) in C1D1

Statistical analysis description

Comparison of effect of food on Tmax between Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 7 Dose Escalation v Phase 1A: Cohort 10 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[32]

P-value

= 0.827259

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges-Lehmann Estimator

Point estimate

-0.45

Confidence interval

level

90%

sides

2-sided

lower limit

-2.467

upper limit

0.95

Notes
[32] - The Hodges-Lehmann estimator and 90% CI was calculated using the Moses approximation.

Comparison of Cohorts 7 and 10 (120 mg) in C2D1

Statistical analysis description

Comparison of effect of food on Tmax between Cohort 7 (fed state) and Cohort 10 (fasted state) treatment arm groups of 120 mg ASTX029 in C1D1.

Comparison groups

Phase 1A: Cohort 7 Dose Escalation v Phase 1A: Cohort 10 Dose Escalation

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

superiority ^[33]

P-value

= 0.51269

Method

Wilcoxon (Mann-Whitney)

Parameter type

Hodges-Lehmann Estimator

Point estimate

0.583

Confidence interval

level

90%

sides

2-sided

lower limit

-6.45

upper limit

3.5

Notes
[33] - The Hodges-Lehmann estimator and 90% CI was calculated using the Moses approximation.

Secondary: Phase 1: Inhibition of Phosphorylated Ribosomal S6 Kinase (pRSK) Protein in Response to ASTX029 Treatment in Tumor Biopsies as assessed by H Score

Top of page

End point title

Phase 1: Inhibition of Phosphorylated Ribosomal S6 Kinase (pRSK) Protein in Response to ASTX029 Treatment in Tumor Biopsies as assessed by H Score ^[34]

End point description

The protein expression level is quantified through the H-score, calculated from staining intensity within the target cell region. H-Score = (3x % of cells with staining graded 3) + (2x % of cells with staining graded 2) + % of cells with staining graded 1. H-Score ranges between 0 to 300. The H-score is for sum of cytoplasmic H-Score (C pRSK H-Score) and nuclear H-Scores (N pRSK H-Score). C pRSK H-Scores, and nuclear H-Scores were combined to give a single H-score. Pharmacodynamics analysis set included in the pharmacodynamic and biomarker analyses if they have received study drug and their samples were successfully collected and analysed. Subjects analysed is the number of subjects with data available for analysis. The data for this end point was collected and analysed for Phase 1B Dose Expansion cohort only.

End point type

Secondary

End point timeframe

4 hours post-dose on Day 8 of Cycle 2 (Cycle length = 21 days)

Notes
[34] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 1B Dose Expansion
Number of subjects analysed	8
Units: score on a scale
arithmetic mean (standard deviation)	181.6 ( 172.31 )

No statistical analyses for this end point

Secondary: Phase 1: Progression Free Survival (PFS)

Top of page

End point title

Phase 1: Progression Free Survival (PFS) ^[35]

End point description

The PFS was defined as the number of months from the start of the study treatment to disease progression or death, whichever occurs first. The PFS was analysed using a Kaplan-Meier method, with PFS time being censored on the date of the last disease assessment. The 90% CI for median PFS was provided using the Kaplan-Meier procedure. The efficacy analysis set included all subjects who received any amount of study drug. Here, "99999" indicates that the upper limit of 95% CI was not estimable because there was no event time for which the upper bound of the CI for the Kaplan-Meier estimate was less than 0.5.

End point type

Secondary

End point timeframe

Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)

Notes
[35] - 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: The data is reported only for the treatment arm groups applicable for this end point.

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 1B Dose Expansion

Number of subjects analysed

Units: months

median (confidence interval 95%)

1.3 (1.2 to 99999)

1.2 (1.2 to 99999)

8.1 (2.7 to 99999)

2.0 (1.1 to 99999)

1.2 (0.2 to 4.8)

1.3 (0.9 to 99999)

3.0 (1.2 to 99999)

1.1 (1.0 to 99999)

1.3 (1.0 to 99999)

2.3 (1.4 to 99999)

3.0 (0.7 to 5.3)

2.5 (0.4 to 4.0)

1.4 (1.2 to 4.2)

No statistical analyses for this end point

Secondary: Phase 1: Overall Survival (OS)

Top of page

End point title

Phase 1: Overall Survival (OS) ^[36]

End point description

The OS was defined as the number of months from the day the subjects was randomised to the date of death (regardless of cause). Subjects without a documented death date were censored on the last date they were known to be alive. The OS was presented using a Kaplan-Meier estimate. The 90% CI for median OS was provided using the Kaplan-Meier procedure. The efficacy analysis set included all subjects who received any amount of study drug. Here, "99999" indicates that the median was not reached, and the lower limit and upper limit of 95% CI was not estimable because there was no event time for which the upper bound of the CI for the Kaplan-Meier estimate was less than 0.5.

End point type

Secondary

End point timeframe

Up to 82 months

Notes
[36] - 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: The data is reported only for the treatment arm groups applicable for this end point.

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 1B Dose Expansion

Number of subjects analysed

Units: months

median (confidence interval 95%)

13.5 (4.4 to 99999)

4.5 (3.4 to 99999)

10.2 (4.1 to 99999)

3.8 (2.1 to 99999)

2.1 (0.5 to 25.5)

11.3 (4.8 to 99999)

8.7 (2.6 to 99999)

2.0 (1.1 to 99999)

10.9 (1.3 to 99999)

99999 (-99999 to 99999)

14.8 (2.7 to 99999)

2.5 (1.2 to 13.1)

15.1 (2.7 to 26.3)

No statistical analyses for this end point

Secondary: Phase 1: Disease Control Rate (DCR)

Top of page

End point title

Phase 1: Disease Control Rate (DCR) ^[37]

End point description

DCR was calculated as number of subjects whose best response was CR, PR, or stable disease (SD), divided by the total number of subjects evaluable for DCR analysis. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target/nontarget) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters while on study. The efficacy analysis set included all subjects who received any amount of study drug. Analysis was based on subjects who were in efficacy analysis set and who had disease assessment at baseline and at least 1 follow-up disease assessment or subjects who died/stopped treatment. Percentages were rounded off to nearest single decimal place.

End point type

Secondary

End point timeframe

Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)

Notes
[37] - 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: The data is reported only for the treatment arm groups applicable for this end point.

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 1B Dose Expansion

Number of subjects analysed

Units: percentage of subjects

number (confidence interval 90%)

0 (0 to 63.2)

100 (36.8 to 100)

40.0 (7.6 to 81.1)

20.0 (3.7 to 50.7)

16.7 (0.9 to 58.2)

66.7 (13.5 to 98.3)

33.3 (1.7 to 86.5)

85.7 (47.9 to 99.3)

42.9 (12.9 to 77.5)

30.0 (14 to 50.8)

No statistical analyses for this end point

Secondary: Phase 1: Duration of Response (DoR)

Top of page

End point title

Phase 1: Duration of Response (DoR) ^[38]

End point description

Duration of response was calculated for all responders from the date of the earliest assessment of CR or PR to the date of relapse or death, whichever occurred earlier, or the last disease assessment date for subjects without a relapse or death. Duration of SD was calculated for subjects whose best response is CR, PR, or SD from the day study drug was first taken to the date of disease progression or death, whichever occurred earlier, or the last disease assessment for subjects without disease progression or death. The efficacy analysis set included all subjects who received any amount of study drug. Subjects analysed is the number of subjects with data available for analysis.

End point type

Secondary

End point timeframe

Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)

Notes
[38] - 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: The data is reported only for the treatment arm groups applicable for this end point.

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 1B Dose Expansion

Number of subjects analysed

0 ^[39]

0 ^[40]

0 ^[41]

0 ^[42]

0 ^[43]

0 ^[44]

0 ^[45]

0 ^[46]

0 ^[47]

0 ^[48]

Units: days

median (full range (min-max))

( to )

484.0 (484.0 to 484.0)

61.0 (61.0 to 61.0)

( to )

252.50 (252.0 to 253.0)

Notes
[39] - Data was not estimable due to low number of subjects with events.
[40] - Data was not estimable due to low number of subjects with events.
[41] - Data was not estimable due to low number of subjects with events.
[42] - Data was not estimable due to low number of subjects with events.
[43] - Data was not estimable due to low number of subjects with events.
[44] - Data was not estimable due to low number of subjects with events.
[45] - Data was not estimable due to low number of subjects with events.
[46] - Data was not estimable due to low number of subjects with events.
[47] - Data was not estimable due to low number of subjects with events.
[48] - Data was not estimable due to low number of subjects with events.

No statistical analyses for this end point

Secondary: Phase 2: AUC0-24 of ASTX029

Top of page

End point title

Phase 2: AUC0-24 of ASTX029 ^[49]

End point description

The PK analysis set included all subjects who had received study drug with available plasma concentrations and PK parameters for ASTX029. Subjects analysed is the number of subjects with data available for analysis and 'n' represents unique number of subjects out of all the assessed subjects with data available at the specified timepoint. Here, "99999" indicates that geometric coefficient of variation was not estimable due to low number of subjects at specified time point.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1,2,3,4,6 and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1,2,4 and 8 post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)

Notes
[49] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	24	13	9	9	28	12
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n= 24,13,9,9,28,12)	12200 ( 69.1 )	13000 ( 57.2 )	9570 ( 80.3 )	8730 ( 100.0 )	12000 ( 83.3 )	13400 ( 71.3 )
Cycle 3 Day 1 (C3D1) (n= 15,4,1,4,16,5)	11600 ( 76.1 )	27600 ( 47.3 )	11500 ( 99999 )	12800 ( 36.2 )	12300 ( 88.7 )	15300 ( 52.4 )

No statistical analyses for this end point

Secondary: Phase 2: AUC0-last of ASTX029

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End point title

Phase 2: AUC0-last of ASTX029 ^[50]

End point description

The PK analysis set included all subjects who had received study drug with available plasma concentrations and PK parameters for ASTX029. Here, subjects analysed is the number of subjects with data available for analysis and 'n' represents unique number of subjects out of all the assessed subjects with data available at the specified timepoint.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1,2,3,4,6 and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1,2,4 and 8 post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)

Notes
[50] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	32	15	12	9	32	14
Units: h*ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n= 32,15,12,9,32,14)	12300 ( 70.4 )	15000 ( 68.5 )	7800 ( 81.7 )	8730 ( 100.0 )	11500 ( 80.3 )	12700 ( 66.9 )
C3D1 (n= 19,7,5,5,20,5)	8090 ( 214.2 )	13600 ( 114.5 )	1960 ( 369.9 )	11700 ( 31.5 )	10400 ( 86.4 )	14000 ( 52.1 )

No statistical analyses for this end point

Secondary: Phase 2: AUC0-inf of ASTX029

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End point title

Phase 2: AUC0-inf of ASTX029 ^[51]

End point description

The PK analysis set included all subjects who had received study drug with available plasma concentrations and PK parameters for ASTX029. Here, subjects analysed is the number of subjects with data available for analysis. Data for AUC0-inf was collected and analysed for C1D1 only.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycle 1: and at 0.5,1,2,3,4,6 and 8 hours post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)

Notes
[51] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	28	13	6	7	30	13
Units: h*ng/mL
geometric mean (geometric coefficient of variation)	12500 ( 66.6 )	17100 ( 60.4 )	10700 ( 103.0 )	11800 ( 62.5 )	12500 ( 74.5 )	13300 ( 67.5 )

No statistical analyses for this end point

Secondary: Phase 2: Cmax of ASTX029

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End point title

Phase 2: Cmax of ASTX029 ^[52]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1,2,3,4,6 and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1,2,4 and 8 post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)

Notes
[52] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	32	15	12	9	32	14
Units: ng/mL
geometric mean (geometric coefficient of variation)
C1D1 (n= 32,15,12,9,32,14)	4430 ( 70.9 )	5930 ( 81.3 )	2890 ( 97.7 )	2840 ( 239.4 )	4660 ( 113.6 )	5620 ( 65.7 )
C3D1 (n= 19,7,5,5,20,5)	3280 ( 179.3 )	4730 ( 150.7 )	780 ( 464.1 )	5090 ( 43.5 )	4410 ( 110.4 )	4860 ( 66.8 )

No statistical analyses for this end point

Secondary: Phase 2: Cmin of ASTX029

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End point title

Phase 2: Cmin of ASTX029 ^[53]

End point description

The PK analysis set included all subjects who had received study drug with available plasma concentrations and PK parameters for ASTX029. Here, subjects analysed is the number of subjects with data available for analysis. Data for Cmin was calculated and analysed for C3D1 only.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycle 3; and at 0.5,1,2,4 and 8 post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)

Notes
[53] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	19	7	5	5	20	5
Units: ng/mL
geometric mean (geometric coefficient of variation)	189 ( 181.0 )	260 ( 95.5 )	81.7 ( 102.0 )	144 ( 78.2 )	205 ( 104.9 )	246 ( 67.6 )

No statistical analyses for this end point

Secondary: Phase 2: Tmax of ASTX029

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End point title

Phase 2: Tmax of ASTX029 ^[54]

End point description

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycles 1, and 3; at 0.5,1,2,3,4,6 and 8 hours post-dose on Day 1 of Cycle 1, and at 0.5,1,2,4 and 8 post-dose on Day 1 of Cycle 3 (Cycle length = 21 days)

Notes
[54] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	32	15	12	9	32	14
Units: hours
median (full range (min-max))
C1D1 (n= 32,15,12,9,32,14)	2.03 (0.50 to 4.08)	1.95 (0.95 to 6.08)	2.90 (0.50 to 7.55)	2.07 (0.92 to 7.90)	2.00 (0.40 to 4.07)	2.00 (1.00 to 3.87)
C3D1 (n= 19,7,5,5,20,5)	2.00 (0.97 to 4.05)	2.03 (0.58 to 4.05)	2.03 (0.67 to 7.53)	1.90 (1.00 to 2.00)	2.00 (0.48 to 4.17)	1.97 (0.95 to 4.00)

No statistical analyses for this end point

Secondary: Phase 2: T1/2 of ASTX029

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End point title

Phase 2: T1/2 of ASTX029 ^[55]

End point description

The PK analysis set included all subjects who had received study drug with available plasma concentrations and PK parameters for ASTX029. Here, subjects analysed is the number of subjects with data available for analysis. Data for T1/2 was collected and analysed for C1D1 only.

End point type

Secondary

End point timeframe

Pre-dose on Day 1 of Cycle 1; at 0.5,1,2,3,4,6 and 8 hours post-dose on Day 1 of Cycle 1 (Cycle length = 21 days)

Notes
[55] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	28	13	6	7	30	13
Units: hours
geometric mean (geometric coefficient of variation)	2.68 ( 68.8 )	3.45 ( 52.0 )	3.79 ( 19.1 )	3.73 ( 12.2 )	3.64 ( 43.2 )	3.39 ( 48.2 )

No statistical analyses for this end point

Secondary: Phase 2: Progression Free Survival

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End point title

Phase 2: Progression Free Survival ^[56]

End point description

End point type

Secondary

End point timeframe

Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)

Notes
[56] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	32	15	12	9	32	14
Units: months
median (confidence interval 95%)	2.8 (1.5 to 5.5)	2.8 (0.9 to 4.6)	1.7 (0.8 to 6.1)	8.0 (1.0 to 9.6)	3.5 (2.2 to 6.2)	2.0 (1.2 to 5.5)

No statistical analyses for this end point

Secondary: Phase 2: Overall Survival

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End point title

Phase 2: Overall Survival ^[57]

End point description

The OS was defined as the number of months from the months the subjects was randomised to the date of death (regardless of cause). Subjects without a documented death date were censored on the last date they were known to be alive. The OS was presented using a Kaplan-Meier estimate. The 90% CI for median OS was provided using the Kaplan-Meier procedure. The efficacy analysis set included all subjects who received any amount of study drug. Here, "99999" indicates that the upper limit of 95% CI was not estimable because there was no event time for which the upper bound of the CI for the Kaplan-Meier estimate was less than 0.5.

End point type

Secondary

End point timeframe

Up to 82 months

Notes
[57] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	32	15	12	9	32	14
Units: months
median (confidence interval 95%)	8.0 (4.4 to 13.6)	4.9 (1.5 to 10.1)	6.1 (1.1 to 19.3)	11.6 (2.0 to 99999)	11.2 (6.8 to 99999)	9.9 (3.5 to 15.9)

No statistical analyses for this end point

Secondary: Phase 2: Disease Control Rate

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End point title

Phase 2: Disease Control Rate ^[58]

End point description

DCR was calculated as number of subjects whose best response was CR, PR, or SD, divided by the total number of subjects evaluable for DCR analysis. CR was defined as disappearance of all target lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. The efficacy analysis set included all subjects who received any amount of study drug. The DCR analysis was based on subjects who were in the efficacy analysis set and 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

Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)

Notes
[58] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	32	15	12	9	32	14
Units: percentage of subjects
number (confidence interval 95%)	65.6 (49.6 to 79.4)	60.0 (36 to 80.9)	41.7 (18.1 to 68.5)	77.8 (45 to 95.9)	68.8 (52.8 to 82)	42.9 (20.6 to 67.5)

No statistical analyses for this end point

Secondary: Phase 2: Duration of Response

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End point title

Phase 2: Duration of Response ^[59]

End point description

End point type

Secondary

End point timeframe

Every 2 cycles for the first 4 cycles and then every 4 cycles thereafter until disease progression (Up to 82 months)

Notes
[59] - 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: The data is reported only for the treatment arm groups applicable for this end point.

End point values	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Number of subjects analysed	4	0 ^[60]	1	0 ^[61]	4	1
Units: days
median (full range (min-max))	193.00 (65.0 to 219.0)	( to )	144.00 (144.00 to 144.00)	( to )	189.50 (102.0 to 260.0)	750.00 (750.00 to 750.00)

Notes
[60] - Data was not estimable due to low number of subjects with events.
[61] - Data was not estimable due to low number of subjects with events.

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

From first dose of study drug up to end of the study (Up to 82 months)

Adverse event reporting additional description

The safety analysis set included data from all subjects who received any amount of study drug.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

27.0

Reporting group title

Phase 1A: Cohort 1 Dose Escalation

Reporting group description

Subjects received ASTX029 10 milligrams (mg), powder in bottle (PiB), orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 2 Dose Escalation

Reporting group description

Subjects received ASTX029 20 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 3 Dose Escalation

Reporting group description

Subjects received ASTX029 60 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 4 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, PiB, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 5 Dose Escalation

Reporting group description

Subjects received ASTX029 200 mg, orally, PiB, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 6 Dose Escalation

Reporting group description

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 7 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fed state.

Reporting group title

Phase 1A: Cohort 8 Dose Escalation

Reporting group description

Subjects received ASTX029 40 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 9 Dose Escalation

Reporting group description

Subjects received ASTX029 80 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 10 Dose Escalation

Reporting group description

Subjects received ASTX029 120 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 11 Dose Escalation

Reporting group description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1A: Cohort 12 Dose Escalation

Reporting group description

Subjects received ASTX029 280 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 1B Dose Expansion

Reporting group description

Subjects received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months, under fasted state.

Reporting group title

Phase 2: Cohort A

Reporting group description

Subjects with neuroblastoma RAS (NRAS)-mutant melanoma received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Reporting group title

Phase 2: Cohort B

Reporting group description

Reporting group title

Phase 2: Cohort C

Reporting group description

Reporting group title

Phase 2: Cohort D

Reporting group description

Subjects with BRAF-fusion cancers received ASTX029 200 mg, tablets, orally, once daily, on Days 1-21 of each 21-day cycle, up to median duration of 1.6 months.

Reporting group title

Phase 2: Cohort E

Reporting group description

Reporting group title

Phase 2: Cohort F

Reporting group description

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 1B Dose Expansion

Phase 2: Cohort A

Phase 2: Cohort B

Phase 2: Cohort C

Phase 2: Cohort D

Phase 2: Cohort E

Phase 2: Cohort F

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 3 (0.00%)

1 / 3 (33.33%)

2 / 3 (66.67%)

2 / 5 (40.00%)

7 / 10 (70.00%)

1 / 6 (16.67%)

2 / 3 (66.67%)

0 / 3 (0.00%)

1 / 3 (33.33%)

3 / 7 (42.86%)

1 / 7 (14.29%)

9 / 20 (45.00%)

11 / 32 (34.38%)

5 / 15 (33.33%)

4 / 12 (33.33%)

3 / 9 (33.33%)

12 / 32 (37.50%)

4 / 14 (28.57%)

number of deaths (all causes)

number of deaths resulting from adverse events

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

Cancer pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Embolism

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Embolism venous

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aortic dissection

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Hypertension

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

1 / 14 (7.14%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hypotension

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Non-cardiac chest pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Malaise

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyrexia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (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

Chest pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Fatigue

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Organ failure

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Respiratory, thoracic and mediastinal disorders

Acute respiratory failure

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Pneumonitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aspiration

subjects affected / exposed

0 / 3 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory failure

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory disorder

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Dyspnoea

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

1 / 12 (8.33%)

0 / 9 (0.00%)

0 / 32 (0.00%)

1 / 14 (7.14%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

1 / 12 (8.33%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (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

Pulmonary embolism

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hypoxia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Haemoptysis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

1 / 12 (8.33%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Wheezing

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Psychiatric disorders

Mental status changes

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Investigations

Alanine aminotransferase increased

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Aspartate aminotransferase increased

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal stoma output decreased

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (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 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

1 / 14 (7.14%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Fracture

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

1 / 12 (8.33%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Hip fracture

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Atrial fibrillation

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Atrial flutter

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Intracranial mass

subjects affected / exposed

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Encephalopathy

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ischaemic stroke

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cerebrovascular accident

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

1 / 14 (7.14%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

0 / 1

Blood and lymphatic system disorders

Anaemia

subjects affected / exposed

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

1 / 9 (11.11%)

0 / 32 (0.00%)

0 / 14 (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

Leukocytosis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal obstruction

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

1 / 12 (8.33%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

0 / 1

0 / 0

Large intestinal obstruction

subjects affected / exposed

0 / 3 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (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

Erosive duodenitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Upper gastrointestinal haemorrhage

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Ascites

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (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

0 / 1

0 / 0

Colitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nausea

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Constipation

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal haemorrhage

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Vomiting

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

1 / 32 (3.13%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (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

Diarrhoea

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

2 / 32 (6.25%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

1 / 14 (7.14%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Abdominal pain upper

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

1 / 9 (11.11%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Abdominal strangulated hernia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastritis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

1 / 14 (7.14%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Inguinal hernia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Intestinal perforation

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (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

Pancreatitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

1 / 7 (14.29%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

2 / 14 (14.29%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 5

deaths causally related to treatment / all

0 / 0

0 / 1

Hydronephrosis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Renal impairment

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Back pain

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Infections and infestations

Pneumonia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

4 / 10 (40.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 4

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Enterocolitis infectious

subjects affected / exposed

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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 / 3 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 3

0 / 0

deaths causally related to treatment / all

0 / 0

Wound infection

subjects affected / exposed

0 / 3 (0.00%)

1 / 5 (20.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Sepsis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

1 / 7 (14.29%)

0 / 20 (0.00%)

2 / 32 (6.25%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Urinary tract infection bacterial

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 7 (14.29%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Biliary tract infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

1 / 6 (16.67%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

1 / 9 (11.11%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device related infection

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia aspiration

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

1 / 9 (11.11%)

0 / 32 (0.00%)

0 / 14 (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 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

1 / 32 (3.13%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pyelonephritis

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

1 / 32 (3.13%)

0 / 14 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Metabolism and nutrition disorders

Hypoglycaemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

1 / 10 (10.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Hyponatraemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

1 / 3 (33.33%)

0 / 3 (0.00%)

0 / 7 (0.00%)

1 / 20 (5.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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

Hyperglycaemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

0 / 15 (0.00%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

1 / 14 (7.14%)

occurrences causally related to treatment / all

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Hyperkalaemia

subjects affected / exposed

0 / 3 (0.00%)

0 / 5 (0.00%)

0 / 10 (0.00%)

0 / 6 (0.00%)

0 / 3 (0.00%)

0 / 7 (0.00%)

0 / 20 (0.00%)

0 / 32 (0.00%)

1 / 15 (6.67%)

0 / 12 (0.00%)

0 / 9 (0.00%)

0 / 32 (0.00%)

0 / 14 (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	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 1B Dose Expansion	Phase 2: Cohort A	Phase 2: Cohort B	Phase 2: Cohort C	Phase 2: Cohort D	Phase 2: Cohort E	Phase 2: Cohort F
Total subjects affected by non serious adverse events
subjects affected / exposed	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	5 / 5 (100.00%)	8 / 10 (80.00%)	6 / 6 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	3 / 3 (100.00%)	7 / 7 (100.00%)	7 / 7 (100.00%)	20 / 20 (100.00%)	31 / 32 (96.88%)	15 / 15 (100.00%)	12 / 12 (100.00%)	9 / 9 (100.00%)	32 / 32 (100.00%)	13 / 14 (92.86%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Tumour pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	2	0	0	0	0	0	0	0	0	0	1	1	0	0	0	2	0
Cancer pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	1 / 12 (8.33%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	1	0	1	0	0	0	1	2	0	0	1	1	0	2	0
Phlebitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Deep vein thrombosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hypertension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 20 (5.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	1 / 12 (8.33%)	1 / 9 (11.11%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	1	0	3	1	2	1
Peripheral coldness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Lymphoedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Embolism
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Hot flush
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	6 / 32 (18.75%)	1 / 15 (6.67%)	0 / 12 (0.00%)	1 / 9 (11.11%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	1	0	0	1	0	0	0	0	1	0	0	0	7	1	0	1	6	1
Chills
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	3 / 20 (15.00%)	2 / 32 (6.25%)	2 / 15 (13.33%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	3	3	2	0	0	2	2
Fatigue
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	2 / 3 (66.67%)	5 / 7 (71.43%)	3 / 7 (42.86%)	7 / 20 (35.00%)	10 / 32 (31.25%)	4 / 15 (26.67%)	3 / 12 (25.00%)	5 / 9 (55.56%)	15 / 32 (46.88%)	6 / 14 (42.86%)
occurrences all number	0	1	2	0	2	0	0	1	1	2	5	4	9	15	7	4	6	25	6
Non-cardiac chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	0	0
Oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	4 / 20 (20.00%)	5 / 32 (15.63%)	2 / 15 (13.33%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	4	8	2	0	0	2	2
Catheter site erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Generalised oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Malaise
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Nodule
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	1	0	0	0	0	1
Oedema peripheral
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	3 / 20 (15.00%)	5 / 32 (15.63%)	1 / 15 (6.67%)	1 / 12 (8.33%)	2 / 9 (22.22%)	6 / 32 (18.75%)	3 / 14 (21.43%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	3	0	3	6	1	2	2	7	6
Secretion discharge
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Catheter site pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Chest discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Injection site bruising
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Localised oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0
Pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	0	0	0
Face oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Thirst
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Gait disturbance
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Peripheral swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Immune system disorders
Hypersensitivity
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	2 / 14 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	0	2
Drug hypersensitivity
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Reproductive system and breast disorders
Balanoposthitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Breast pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pelvic pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 20 (10.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	6	0	0	0
Productive cough
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	0	0	2	0
Cough
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	3 / 32 (9.38%)	1 / 15 (6.67%)	0 / 12 (0.00%)	2 / 9 (22.22%)	3 / 32 (9.38%)	1 / 14 (7.14%)
occurrences all number	0	0	1	0	0	0	0	0	1	0	0	0	1	3	1	0	2	4	1
Dysphonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Wheezing
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Dyspnoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	2 / 20 (10.00%)	3 / 32 (9.38%)	2 / 15 (13.33%)	2 / 12 (16.67%)	3 / 9 (33.33%)	4 / 32 (12.50%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	1	2	3	3	3	5	4	2
Epistaxis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	2 / 14 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	1	1	1	0	0	2	2
Nasal congestion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	2	0
Pneumothorax
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hypercapnia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hypoxia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	2	0	0	0
Lung opacity
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Nasal dryness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Pneumonitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0	0	0	1	1	0	0	0	0
Tachypnoea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Hiccups
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	1	0
Dyspnoea exertional
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Chronic obstructive pulmonary disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Haemoptysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Laryngeal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Respiratory distress
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	1	0	0	0	0	0	0	2	0
Delirium
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Confusional state
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	1	0	0	0	0
Agitation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0	0	0
Mental status changes
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Anxiety
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	2	1
Depression
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Mental disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Sleep disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0	0
Investigations
Aspartate aminotransferase increased
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 5 (20.00%)	5 / 10 (50.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	2 / 7 (28.57%)	1 / 7 (14.29%)	2 / 20 (10.00%)	6 / 32 (18.75%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	3 / 32 (9.38%)	2 / 14 (14.29%)
occurrences all number	1	0	1	1	6	3	0	1	0	2	2	1	2	9	0	0	0	6	3
Alanine aminotransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	3 / 10 (30.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 3 (66.67%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 20 (5.00%)	5 / 32 (15.63%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	6 / 32 (18.75%)	0 / 14 (0.00%)
occurrences all number	0	0	0	2	3	1	0	1	0	2	1	0	1	6	1	0	0	11	0
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 3 (33.33%)	2 / 3 (66.67%)	0 / 3 (0.00%)	1 / 5 (20.00%)	2 / 10 (20.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 20 (0.00%)	3 / 32 (9.38%)	2 / 15 (13.33%)	0 / 12 (0.00%)	2 / 9 (22.22%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	2	2	0	2	2	1	0	1	0	0	1	1	0	7	2	0	2	2	0
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1	1	1	0	0	0	1	0	1	0	0	0	0	0	0	1
Blood cholesterol increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	0	0	0	1	0	0	0	1	0
Lipase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	3	1	0	0	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	3 / 32 (9.38%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	2	0	0	1	2	0	0	4	0
Weight decreased
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	1 / 12 (8.33%)	1 / 9 (11.11%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	0	2	1	2	0	1
Blood glucose increased
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
White blood cell count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	1	1	0	1	0	0	0	2	0
International normalised ratio increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	2	0
Blood creatinine increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 20 (5.00%)	3 / 32 (9.38%)	0 / 15 (0.00%)	0 / 12 (0.00%)	2 / 9 (22.22%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	1	2	1	0	0	1	0	1	3	0	0	2	2	1
Ammonia increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Blood magnesium decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2	0	0
Ejection fraction decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	3 / 32 (9.38%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	5	0	0	1	2	0
Weight increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1	1
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	3 / 32 (9.38%)	1 / 15 (6.67%)	0 / 12 (0.00%)	1 / 9 (11.11%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1	0	1	1	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	2 / 15 (13.33%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	0	0
Amylase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1	0	0	0	0
Blood corticotrophin decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Blood creatine increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Blood iron decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Blood potassium increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hepatic enzyme increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Neutrophil count decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 20 (5.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	1	1	1	0	0	0	1
Post procedural complication
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Post procedural discharge
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Stoma site haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Post procedural contusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Venous injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Spinal compression fracture
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Limb injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Skin abrasion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Congenital, familial and genetic disorders
Phimosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	4 / 32 (12.50%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	0	0	1	0	0	6	0
Tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0	1	0
Angina pectoris
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Supraventricular tachycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0	0	0	0	0	0
Sinus bradycardia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0
Nervous system disorders
Dysgeusia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	2 / 15 (13.33%)	0 / 12 (0.00%)	1 / 9 (11.11%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	1	0	2	0	0	0	0	0	0	0	0	0	2	0	1	1	1
Memory impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Neuralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dizziness
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	2 / 7 (28.57%)	1 / 20 (5.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	2 / 12 (16.67%)	1 / 9 (11.11%)	4 / 32 (12.50%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	2	2	1	0	2	1	4	0
Migraine
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Ophthalmic migraine
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Burning sensation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Headache
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	2 / 20 (10.00%)	4 / 32 (12.50%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	3 / 32 (9.38%)	2 / 14 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	1	2	4	0	0	0	3	2
Neuropathy peripheral
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Post herpetic neuralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Sciatica
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	3	0	0	0	0	0	0
Seizure
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Somnolence
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1	1	0	0	0	0
Tremor
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Paraesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 20 (10.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	1	0	0	0	0	1
Aphasia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Embolic stroke
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Balance disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0
Syncope
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Dizziness postural
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	2 / 3 (66.67%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 5 (40.00%)	3 / 10 (30.00%)	0 / 6 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	3 / 7 (42.86%)	7 / 20 (35.00%)	9 / 32 (28.13%)	3 / 15 (20.00%)	5 / 12 (41.67%)	2 / 9 (22.22%)	14 / 32 (43.75%)	5 / 14 (35.71%)
occurrences all number	2	3	0	2	4	0	3	0	0	1	0	4	8	17	3	8	4	42	15
Leukocytosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Neutropenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	4	0	1	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	1	0	0	1
Anaemia of malignant disease
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Lymphopenia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Thrombocytosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Iron deficiency anaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Thrombotic thrombocytopenic purpura
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Middle ear effusion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Tinnitus
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Inner ear disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Eye disorders
Dyschromatopsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Periorbital oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Photophobia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0	0	0	0	0	0	2	0	0	0	0	0
Vision blurred
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	3 / 7 (42.86%)	2 / 7 (28.57%)	2 / 20 (10.00%)	5 / 32 (15.63%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	4 / 32 (12.50%)	4 / 14 (28.57%)
occurrences all number	0	0	0	1	1	0	0	0	1	0	3	3	3	7	0	0	1	4	5
Visual field defect
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Retinal degeneration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Cataract
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Diplopia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	2 / 20 (10.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	2	0	0	0	0	0	0
Macular detachment
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Retinopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	1	1	0	0	0	0
Visual impairment
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	2 / 20 (10.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	1 / 9 (11.11%)	3 / 32 (9.38%)	2 / 14 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	1	3	1	1	0	1	5	2
Central serous chorioretinopathy
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	4	0	0	1	0	1
Detachment of retinal pigment epithelium
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Exophthalmos
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Subretinal fluid
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	0	0	0
Visual acuity reduced
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Eye disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Retinal detachment
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0	0	1
Presbyopia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Vitreous floaters
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Blepharitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Keratitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Lacrimation increased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Ocular discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Visual brightness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Gastrointestinal disorders
Nausea
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	3 / 3 (100.00%)	3 / 5 (60.00%)	4 / 10 (40.00%)	1 / 6 (16.67%)	2 / 3 (66.67%)	2 / 3 (66.67%)	1 / 3 (33.33%)	2 / 3 (66.67%)	3 / 7 (42.86%)	3 / 7 (42.86%)	7 / 20 (35.00%)	10 / 32 (31.25%)	8 / 15 (53.33%)	5 / 12 (41.67%)	4 / 9 (44.44%)	15 / 32 (46.88%)	3 / 14 (21.43%)
occurrences all number	0	1	4	3	5	1	2	2	1	2	3	4	13	15	12	6	6	19	3
Diarrhoea
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 5 (20.00%)	3 / 10 (30.00%)	2 / 6 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	3 / 7 (42.86%)	4 / 7 (57.14%)	10 / 20 (50.00%)	19 / 32 (59.38%)	6 / 15 (40.00%)	5 / 12 (41.67%)	6 / 9 (66.67%)	23 / 32 (71.88%)	8 / 14 (57.14%)
occurrences all number	0	1	2	2	4	2	0	0	2	1	3	9	22	40	6	6	10	40	14
Constipation
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	3 / 20 (15.00%)	5 / 32 (15.63%)	2 / 15 (13.33%)	0 / 12 (0.00%)	2 / 9 (22.22%)	4 / 32 (12.50%)	3 / 14 (21.43%)
occurrences all number	0	1	0	0	2	0	0	0	0	1	0	0	3	5	3	0	3	5	3
Abdominal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	5 / 20 (25.00%)	9 / 32 (28.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	3 / 9 (33.33%)	1 / 32 (3.13%)	2 / 14 (14.29%)
occurrences all number	0	0	0	0	1	0	2	1	1	0	1	1	5	12	0	0	4	1	2
Lip oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Vomiting
subjects affected / exposed	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 5 (40.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	1 / 3 (33.33%)	3 / 7 (42.86%)	1 / 7 (14.29%)	6 / 20 (30.00%)	6 / 32 (18.75%)	4 / 15 (26.67%)	5 / 12 (41.67%)	2 / 9 (22.22%)	13 / 32 (40.63%)	3 / 14 (21.43%)
occurrences all number	1	1	0	3	1	1	0	1	2	1	4	1	9	9	5	6	4	19	3
Abdominal discomfort
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Ascites
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	1	0	0	1	0	0	2	0
Dry mouth
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	5 / 20 (25.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	1 / 9 (11.11%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	1	0	0	5	3	1	0	1	2	0
Dysphagia
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	1 / 32 (3.13%)	2 / 15 (13.33%)	2 / 12 (16.67%)	1 / 9 (11.11%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	1	1	2	2	1	0	1
Ileus
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Gastric ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0	1
Abdominal distension
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 20 (10.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0	0	0	3	1
Cheilitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Dyspepsia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	3 / 32 (9.38%)	1 / 15 (6.67%)	0 / 12 (0.00%)	2 / 9 (22.22%)	5 / 32 (15.63%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	4	1	0	2	6	1
Lower gastrointestinal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Oral dysaesthesia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1	0	0	0
Swollen tongue
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Abdominal pain upper
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 20 (10.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	2 / 9 (22.22%)	2 / 32 (6.25%)	3 / 14 (21.43%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	2	0	0	2	3	6
Rectal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0	0
Gastrointestinal haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Glossodynia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Large intestinal ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Large intestinal polyp
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Melaena
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
Stomatitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	3 / 32 (9.38%)	2 / 15 (13.33%)	0 / 12 (0.00%)	1 / 9 (11.11%)	3 / 32 (9.38%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	3	3	0	2	3	1
Tongue oedema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2	0
Retching
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0
Angular cheilitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Colitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Gastritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2
Lip blister
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Odynophagia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Oesophagitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Small intestinal obstruction
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Tongue haemorrhage
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Toothache
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Hepatobiliary disorders
Hepatic pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Hyperbilirubinaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Hypertransaminasaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Skin and subcutaneous tissue disorders
Pruritus
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	6 / 32 (18.75%)	2 / 15 (13.33%)	3 / 12 (25.00%)	1 / 9 (11.11%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	1	0	0	0	2	0	0	0	0	0	0	1	0	11	2	3	1	2	1
Rash maculo-papular
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	4 / 20 (20.00%)	4 / 32 (12.50%)	4 / 15 (26.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	4	1	2	1	0	0	2	2	6	4	4	0	0	6	1
Alopecia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	2 / 32 (6.25%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	4 / 32 (12.50%)	3 / 14 (21.43%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0	1	0	2	1	0	0	5	3
Erythema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Onychoclasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 7 (28.57%)	0 / 7 (0.00%)	2 / 20 (10.00%)	7 / 32 (21.88%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	4 / 32 (12.50%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	2	0	2	8	1	0	0	9	1
Dermatitis acneiform
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	2 / 7 (28.57%)	3 / 20 (15.00%)	6 / 32 (18.75%)	4 / 15 (26.67%)	3 / 12 (25.00%)	1 / 9 (11.11%)	9 / 32 (28.13%)	2 / 14 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	2	3	12	4	2	1	10	2
Rash
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	3 / 7 (42.86%)	2 / 7 (28.57%)	4 / 20 (20.00%)	6 / 32 (18.75%)	2 / 15 (13.33%)	0 / 12 (0.00%)	0 / 9 (0.00%)	3 / 32 (9.38%)	3 / 14 (21.43%)
occurrences all number	0	0	0	0	0	1	0	0	0	1	3	2	4	16	2	0	0	5	6
Hyperhidrosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Skin fissures
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	2	0	0	0	0	0
Skin indentation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Rash pruritic
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Scab
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Skin hyperpigmentation
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Night sweats
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	3	1	0	0	0	0
Eczema
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	0	0	0	0
Onycholysis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	1
Rosacea
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3
Skin lesion
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Skin ulcer
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1	0
Nail disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Rash macular
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	2	0	0	0	0	2	0	0	0	0	0	1	0	0	0	1
Haematuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	3	0
Chromaturia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	1
Pollakiuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1	0	0
Acute kidney injury
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 20 (10.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	2	0	0	0	0	0	0
Hydronephrosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Proteinuria
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Urinary incontinence
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Pain in extremity
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	3 / 20 (15.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0	0	0	0	1	4	2	0	0	1	1	0
Arthralgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	2 / 7 (28.57%)	1 / 20 (5.00%)	4 / 32 (12.50%)	1 / 15 (6.67%)	1 / 12 (8.33%)	1 / 9 (11.11%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	1	0	0	0	1	0	0	0	0	2	1	5	5	1	1	3	7
Back pain
subjects affected / exposed	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	1 / 20 (5.00%)	5 / 32 (15.63%)	1 / 15 (6.67%)	1 / 12 (8.33%)	0 / 9 (0.00%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	1	1	9	1	1	0	3	2
Flank pain
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	1	0	0	0	0	0	0	0
Joint swelling
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Muscle spasms
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	3 / 32 (9.38%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	2 / 14 (14.29%)
occurrences all number	0	0	0	1	0	0	0	0	0	1	0	5	0	3	0	0	0	2	3
Muscular weakness
subjects affected / exposed	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	1	0	0	1	0	1	0	2	0
Bone pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Limb mass
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Myalgia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	2 / 20 (10.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	2 / 14 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	2	0	0	0	0	1	2
Neck pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Spinal pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	3
Bursitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Connective tissue disorder
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Joint range of motion decreased
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Musculoskeletal stiffness
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Osteonecrosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Osteoporosis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Infections and infestations
Pneumonia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	3	0	0	0	0	1	0	1	0	1	0	0	0	0	1
Paronychia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1	0	1	0	2	0
Skin infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	1	2	1
Urinary tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 7 (28.57%)	0 / 7 (0.00%)	3 / 20 (15.00%)	4 / 32 (12.50%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	7 / 32 (21.88%)	2 / 14 (14.29%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	2	0	5	5	1	0	0	11	2
Wound infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Ear infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Rash pustular
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0	0	0	3	0	1	0	1	0
Bacteraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	2	1	0
Injection site infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	1 / 20 (5.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0
COVID-19
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	5 / 32 (15.63%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	5	0	0	0	2	1
Coronavirus infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	1 / 12 (8.33%)	2 / 9 (22.22%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	2	2	0	1
Rhinitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	2 / 9 (22.22%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	1
Folliculitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Gastroenteritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Herpes zoster
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	1
Lower respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	2	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	1 / 32 (3.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	1
Hordeolum
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Metapneumovirus infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Periorbital infection
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Urethritis
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 7 (14.29%)	3 / 20 (15.00%)	6 / 32 (18.75%)	5 / 15 (33.33%)	2 / 12 (16.67%)	2 / 9 (22.22%)	9 / 32 (28.13%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	1	0	1	0	1	1	0	1	3	7	6	3	2	11	1
Hyperglycaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 20 (5.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	0 / 12 (0.00%)	1 / 9 (11.11%)	6 / 32 (18.75%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	0	5	0	0	2	1	0	1	3	0	0	1	10	0
Hyperkalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	1	0	0	0	0	0	0	0	3	0
Hypoalbuminaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 7 (14.29%)	0 / 7 (0.00%)	1 / 20 (5.00%)	4 / 32 (12.50%)	0 / 15 (0.00%)	1 / 12 (8.33%)	1 / 9 (11.11%)	5 / 32 (15.63%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	2	0	1	4	0	1	1	5	0
Hypocalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	0	0	0	0	0	0	0	2	0
Hyponatraemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	3 / 7 (42.86%)	3 / 20 (15.00%)	1 / 32 (3.13%)	2 / 15 (13.33%)	1 / 12 (8.33%)	0 / 9 (0.00%)	5 / 32 (15.63%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	1	1	4	0	0	1	0	3	4	1	2	1	0	6	0
Dehydration
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 5 (40.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	2 / 7 (28.57%)	2 / 20 (10.00%)	2 / 32 (6.25%)	3 / 15 (20.00%)	1 / 12 (8.33%)	1 / 9 (11.11%)	5 / 32 (15.63%)	0 / 14 (0.00%)
occurrences all number	0	0	0	3	0	0	0	0	0	0	0	2	2	2	3	2	1	6	0
Hypokalaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 5 (20.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 7 (28.57%)	1 / 7 (14.29%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	2	1	0	0	1	0	0	0	0
Hypophosphataemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	1 / 7 (14.29%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	1 / 12 (8.33%)	1 / 9 (11.11%)	1 / 32 (3.13%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	2	0	1	0	1	0	1	1	1	0
Hypercalcaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	1 / 32 (3.13%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	1	0	0	0	0	0
Hyperuricaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	0 / 15 (0.00%)	0 / 12 (0.00%)	0 / 9 (0.00%)	2 / 32 (6.25%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0	0	0	0	2	0
Hypomagnesaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	4 / 32 (12.50%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	7 / 32 (21.88%)	1 / 14 (7.14%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	4	3	0	0	7	2
Hypoproteinaemia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	2 / 32 (6.25%)	0 / 15 (0.00%)	1 / 12 (8.33%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	4	0	1	0	0	0
Cachexia
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Malnutrition
subjects affected / exposed	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 5 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 7 (0.00%)	0 / 7 (0.00%)	0 / 20 (0.00%)	0 / 32 (0.00%)	1 / 15 (6.67%)	0 / 12 (0.00%)	0 / 9 (0.00%)	0 / 32 (0.00%)	0 / 14 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	0	1	0	0	0	0

More information

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Were there any global substantial amendments to the protocol? Yes

21 Feb 2019

The following changes were made as per Amendment 1: The protocol was amended to introduce the new tablet dosage form of ASTX029, increase the number of study centres, add Europe as a location of study centres for Phase 1, provide newly available nonclinical study results, and allow for administration of the PiB dosage form of ASTX029 by gastrostomy tube (g-tube). Time windows were provided for certain assessments that were planned to occur at cycle visits to allow more scheduling flexibility for the subjects, investigators, and study centres without impacting subject safety.

12 Jul 2019

The following changes were made as per Amendment 2: The protocol was amended to evaluate dosing of ASTX029 under fasting conditions in Phase 1 Part A as a result of nonclinical data from 3 food-effect studies conducted in monkeys and dogs and preliminary clinical PK data becoming available.

31 Dec 2019

The following changes were made as per Amendment 3: The protocol was amended to modify Phase 2 cohorts and specify Phase 2 evaluations in preparation for initiation of Phase 2 and to remove ASTX029 tablet strength information to accommodate potential additional strengths, which were to be specified in the Investigator Brochure (IB).

21 Jul 2020

The following changes were made as per Amendment 4: The protocol was amended to add language regarding conducting the study during the COVID-19 pandemic to enable continuation of the study during the pandemic, to clarify that Regimen 2 may not need to be evaluated during Phase 1 Part A to determine the regimen to be evaluated in Phase 1 Part B, to specify contraceptive use and conduct of pregnancy tests consistent with requirements of countries other than the US as well as the US, to remove descriptions of the phased out ASTX029 PiB formulation.

23 May 2024

The following changes were made as per Amendment 5: A substantial amendment, updated “Astex Pharmaceuticals, Inc.” and associated references to Astex to “Taiho Oncology, Inc.”, “Taiho”, or “the Sponsor”, as a result of Astex Pharmaceuticals, Inc. becoming a wholly-owned subsidiary of Taiho Oncology Inc.as of 01 January 2024. It also inserted the End of Study definition and added the Study Extension phase.

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.

The ASTX029 clinical development program was terminated by the sponsor due to the changing treatment landscape.

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Clinical trials

Clinical Trial Results: A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects with Advanced Solid Tumors

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Phase 1: Number of Subjects With Dose Limiting Toxicities (DLTs)

Primary: Phase 1: Number of Subjects With Dose Limiting Toxicities (DLTs)

Primary: Phase 1: Number of Subjects with Treatment Emergent Adverse Events (TEAEs)

Primary: Phase 1: Number of Subjects with Treatment Emergent Adverse Events (TEAEs)

Primary: Phase 2: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Primary: Phase 2: Objective Response Rate (ORR) as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX029

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero to 24 Hours (AUC0-24) of ASTX029

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ASTX029

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of ASTX029

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of ASTX029

Secondary: Phase 1: Area Under the Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of ASTX029

Secondary: Phase 1: Maximum Observed Plasma Concentration (Cmax) of ASTX029

Secondary: Phase 1: Maximum Observed Plasma Concentration (Cmax) of ASTX029

Secondary: Phase 1: Minimum Plasma Concentration (Cmin) of ASTX029

Secondary: Phase 1: Minimum Plasma Concentration (Cmin) of ASTX029

Secondary: Phase 1: Time to Reach Maximum Concentration (Tmax) of ASTX029

Secondary: Phase 1: Time to Reach Maximum Concentration (Tmax) of ASTX029

Secondary: Phase 1: Elimination Half-Life (T1/2) of ASTX029

Secondary: Phase 1: Elimination Half-Life (T1/2) of ASTX029

Secondary: Phase 1: Effect of Food on AUC0-24 of ASTX029

Secondary: Phase 1: Effect of Food on AUC0-24 of ASTX029

Secondary: Phase 1: Effect of Food on AUC0-inf of ASTX029

Secondary: Phase 1: Effect of Food on AUC0-inf of ASTX029

Secondary: Phase 1: Effect of Food on Cmax of ASTX029

Secondary: Phase 1: Effect of Food on Cmax of ASTX029

Secondary: Phase 1: Effect of Food on Tmax of ASTX029

Secondary: Phase 1: Effect of Food on Tmax of ASTX029

Secondary: Phase 1: Inhibition of Phosphorylated Ribosomal S6 Kinase (pRSK) Protein in Response to ASTX029 Treatment in Tumor Biopsies as assessed by H Score

Secondary: Phase 1: Inhibition of Phosphorylated Ribosomal S6 Kinase (pRSK) Protein in Response to ASTX029 Treatment in Tumor Biopsies as assessed by H Score

Secondary: Phase 1: Progression Free Survival (PFS)

Secondary: Phase 1: Progression Free Survival (PFS)

Secondary: Phase 1: Overall Survival (OS)

Secondary: Phase 1: Overall Survival (OS)

Secondary: Phase 1: Disease Control Rate (DCR)

Secondary: Phase 1: Disease Control Rate (DCR)

Secondary: Phase 1: Duration of Response (DoR)

Secondary: Phase 1: Duration of Response (DoR)

Secondary: Phase 2: AUC0-24 of ASTX029

Secondary: Phase 2: AUC0-24 of ASTX029

Secondary: Phase 2: AUC0-last of ASTX029

Secondary: Phase 2: AUC0-last of ASTX029

Secondary: Phase 2: AUC0-inf of ASTX029

Secondary: Phase 2: AUC0-inf of ASTX029

Secondary: Phase 2: Cmax of ASTX029

Secondary: Phase 2: Cmax of ASTX029

Secondary: Phase 2: Cmin of ASTX029

Secondary: Phase 2: Cmin of ASTX029

Secondary: Phase 2: Tmax of ASTX029

Secondary: Phase 2: Tmax of ASTX029

Secondary: Phase 2: T1/2 of ASTX029

Secondary: Phase 2: T1/2 of ASTX029

Secondary: Phase 2: Progression Free Survival

Secondary: Phase 2: Progression Free Survival

Secondary: Phase 2: Overall Survival

Secondary: Phase 2: Overall Survival

Secondary: Phase 2: Disease Control Rate

Secondary: Phase 2: Disease Control Rate

Secondary: Phase 2: Duration of Response

Secondary: Phase 2: Duration of Response

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Phase 1-2 Study of the Safety, Pharmacokinetics, and Activity of ASTX029 in Subjects with Advanced Solid Tumors