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Clinical Trial Results:
A Modular, Multi-part, Multi-arm, Open-label, Phase I/IIa Study to Evaluate the Safety and Tolerability of CT7001 Alone and in Combination with Anti-cancer Treatments in Patients with Advanced Malignancies

Summary
EudraCT number	2017-002026-20
Trial protocol	GB
Global end of trial date	15 Dec 2022

Results information
Results version number	v1(current)
This version publication date	31 Mar 2024
First version publication date	31 Mar 2024
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

CT7001-001

ISRCTN number

US NCT number

NCT03363893

WHO universal trial number (UTN)

Sponsor organisation name

Carrick Therapeutics Limited

Sponsor organisation address

Regus Dublin Blanchardstown Block 1, Blanchardstown Corporate Park Ballycoolin Road Blanchardstown, Dublin, Ireland, 15 D15 AKK1

Public contact

Sheila O Mahony, Carrick Therapeutics Limited, +353 1 5996873, trials@carricktherapeutics.com

Scientific contact

Sheila O Mahony, Carrick Therapeutics Limited, +353 1 5996873, trials@carricktherapeutics.com

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

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

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

Analysis stage

Final

Date of interim/final analysis

15 Dec 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

15 Dec 2022

Global end of trial reached?

Yes

Global end of trial date

15 Dec 2022

Was the trial ended prematurely?

Main objective of the trial

Core: To investigate the safety and tolerability of CT7001 given alone or in combination with anticancer treatments Module 1A: To select the CT7001 dose(s) and schedule(s) for further clinical evaluation in patients with advanced solid malignancies. Module 1B-1: To further characterize the safety and tolerability of CT7001 and determine the most appropriate dosing regimen for subsequent Phase 2 testing (definitive recommended Phase 2 dose). Module 1B-2: To assess the biological and anti-tumor activity of CT7001, given as a monotherapy. Module 2A: To determine the recommended Phase 2 dose (RP2D) of CT7001 given in combination with fulvestrant at 500 mg. Module 4: To evaluate the effect of food on the total and peak exposure of CT7001 when dosed as a capsule formulation to patients with advanced solid malignancies

Protection of trial subjects

The study was conducted in accordance with the principles of the Declaration of Helsinki and in compliance with the National Health Service Research Governance Framework, International Council for Harmonization (ICH) Good Clinical Practice (GCP(CPMP/ICH/135/95, Jul 1996) and subsequent R2 amendment, the European Directive on Clinical Trials (2001/20/EC, 04 Apr 2001 and subsequent amendments) and the European Directive on GCP (2005/28/EC). All subjects were provided written informed consent before undergoing any trial related procedures. Safety of the subjects was safeguarded through safety data review and the implementation of study stopping criteria.

Background therapy

Evidence for comparator

Actual start date of recruitment

14 Nov 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United Kingdom: 111

Country: Number of subjects enrolled

United States: 13

Worldwide total number of subjects

124

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

This study recruited participants at least 18 years of age with histological or cytological confirmation of an advanced malignancy, with an Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 and an estimated life expectancy greater than 12 weeks. 25 sites in total, 11 sites in the UK and 14 sites in the US participated in the study.

Screening details

A total of 174 participants were recruited, of which 124 participants were enrolled and went on to receive study treatment with CT7001. Of the 174 participants screened, 50 participants did not receive study treatment, of which 46 participants did not meet the study enrolment criteria and 4 participants withdrew from the study.

Number of subjects started

174 ^[1]

Number of subjects completed

124

Reason: Number of subjects

Consent withdrawn by subject: 4

Reason: Number of subjects

Screening failure: 46

Notes
[1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: A total of 174 participants were recruited, of which 124 participants were enrolled and went on to receive study treatment with CT7001. Of the 174 participants screened, 50 participants did not receive study treatment, of which 46 participants did not meet the study enrolment criteria and 4 participants withdrew from the study.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Module 1 Part A-Cohort 1 120mg OD

Arm description

Participants received a single dose of CT7001 on Day 1 of Cycle 0 (C0D1) followed by a 2-day washout period (C0D2), before receiving cycles of 21 continuous days dosing of CT7001 capsules. Dosing was continued until the participant was no longer gaining clinical benefit or another treatment discontinuation criterion was met, at which time an end of treatment visit was conducted.

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally were taken as a single dose (120 mg for Cohort 1) on Cycle 0 Day 1 with a minimum of a 48-hour washout period following this dose. Cycle 1 dosing then began as a once daily dosing regimen on Cycle 1 Day 1 (C1D1). A cycle of study treatment (after Cycle 0) was for a minimum of 21 days.

Module 1 Part A-Cohort 2 240 mg OD

Arm description

Dose Escalation Phase-Participants received a single dose of CT7001 on Day 1 of Cycle 0 (C0D1) followed by a 2-day washout period (C0D2), before receiving cycles of 21 continuous days dosing of CT7001 capsules. Dosing was continued until the participant was no longer gaining clinical benefit or another treatment discontinuation criterion was met, at which time an end of treatment visit was conducted.Once the MBAD was determined and agreed by the SRC, the paired biopsy expansion cohort in patients with breast cancer commenced at the selected dose

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally were taken as a single dose (240 mg for Cohort 2) on Cycle 0 Day 1 with a minimum of a 48-hour washout period following this dose. Cycle 1 dosing then began as a once daily dosing regimen on Cycle 1 Day 1 (C1D1). A cycle of study treatment (after Cycle 0) was for a minimum of 21 days.

Module 1 Part A-Cohort 3 480 mg OD

Arm description

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally were taken as a single dose (480 mg for Cohort 3) on Cycle 0 Day 1 with a minimum of a 48-hour washout period following this dose. Cycle 1 dosing then began as a once daily dosing regimen on Cycle 1 Day 1 (C1D1). A cycle of study treatment (after Cycle 0) was for a minimum of 21 days.

Module 1 Part A-Cohort 4 360 mg OD

Arm description

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally were taken as a single dose (360 mg for Cohort 4) on Cycle 0 Day 1 with a minimum of a 48-hour washout period following this dose. Cycle 1 dosing then began as a once daily dosing regimen on Cycle 1 Day 1 (C1D1). A cycle of study treatment (after Cycle 0) was for a minimum of 21 days.

Module 1 Part A-Cohort 5 180 mg BID

Arm description

Dose Escalation Phase-Participants received twice daily dose of CT7001 on Day 1 of Cycle 0 (C0D1) followed by a 2-day washout period (C0D2), before receiving cycles of 21 continuous days dosing of CT7001 capsules. Dosing was continued until the participant was no longer gaining clinical benefit or another treatment discontinuation criterion was met, at which time an end of treatment visit was conducted.

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally were taken as 180 mg twice daily (for Cohort 5) on Cycle 0 Day 1 with a minimum of a 48-hour washout period following this dose. Cycle 1 dosing then began as twice daily dosing regimen on Cycle 1 Day 1 (C1D1). A cycle of study treatment (after Cycle 0) was for a minimum of 21 days.

Module 1 Part B-1 360mg OD (TNBC)

Arm description

In this Module 1B-1, CT7001 was administered to participants with advanced TNBC at the maximum tolerated dose (MTD) identified from Module 1A (360 mg once daily [OD]).

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally were taken as 360 mg once daily.

Module 1 Part B-2 360mg OD (CRPC)

Arm description

In this Module 1B-2, CT7001 was administered to participants with advanced CRPC at the maximum tolerated dose (MTD) identified from Module 1A (360 mg once daily [OD]).

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally were taken as 360 mg once daily.

Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)

Arm description

Module 2 was to comprise of 3 parts (A, B and C). This study results summary details the results from Part A, an open-label, single-arm, ascending dose study to determine the dosing regimen of CT7001 and fulvestrant. Part A proved sufficient to inform the next studies to be conducted within the development program, therefore no further details are provided on Parts B and C. In each cohort, the dose of fulvestrant was fixed at the standard dose of 500 mg given at intervals of 28 ±2 days with an additional 500 mg dose given 14 ±2 days after the first dose. Fulvestrant was administered as 2 consecutive slow intramuscular (i.m.) injections (1-2 minutes) of 250 mg in 5 mL, one in each buttock (gluteal area). Cohort 1 tested CT7001 at 240 mg once daily (OD), which is approximately 33% lower than the preliminary RP2D as monotherapy (360 mg).

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally in either a fed or fasted state were taken as 240 mg once daily (OD).

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Fulvestrant 500 mg given at intervals of 28 ±2 days with an additional 500 mg dose given 14 ±2 days after the first dose, administered as 2 consecutive slow intramuscular injections (1-2 minutes) of 250 mg in 5 mL, one in each buttock (gluteal area).

Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)

Arm description

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally in either a fed or fasted state were taken as 360 mg once daily.

Investigational medicinal product name

Fulvestrant

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Intramuscular use

Dosage and administration details

Module 4-120 mg OD

Arm description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Sequence 1: 120 mg CT7001 fed in Period 1 followed by 120 mg CT7001 fasted in Period 2. Sequence 2: 120 mg CT7001 fasted in Period 1 followed by 120 mg CT7001 fed in Period 2.

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 Capsules orally, 120 mg fed in Period 1 followed by 120 mg CT7001 fasted in Period 2, followed by 240 mg once daily (OD) in the continuous dosing phase.

Module 4 360 mg OD

Arm description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Sequence 3: 360 mg CT7001 fed in Period 1 followed by 360 mg CT7001 fasted in Period 2. Sequence 4: 360 mg CT7001 fasted in Period 1 followed by 360 mg CT7001 fed in Period 2.

Arm type

Experimental

Investigational medicinal product name

CT7001

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

CT7001 capsules orally, 360 mg fed in Period 1 followed by 360 mg CT7001 fasted in Period 2, followed by 360 mg once daily (OD) in the continuous dosing phase.

Number of subjects in period 1	Module 1 Part A-Cohort 1 120mg OD	Module 1 Part A-Cohort 2 240 mg OD	Module 1 Part A-Cohort 3 480 mg OD	Module 1 Part A-Cohort 4 360 mg OD	Module 1 Part A-Cohort 5 180 mg BID	Module 1 Part B-1 360mg OD (TNBC)	Module 1 Part B-2 360mg OD (CRPC)	Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)	Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)	Module 4-120 mg OD	Module 4 360 mg OD
Started	6	12	6	12	8	23	11	6	25	8	7
Completed	6	12	6	12	8	23	11	6	25	8	7

Baseline characteristics

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Reporting group title

Module 1 Part A-Cohort 1 120mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 2 240 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 3 480 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 4 360 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 5 180 mg BID

Reporting group description

Reporting group title

Module 1 Part B-1 360mg OD (TNBC)

Reporting group description

In this Module 1B-1, CT7001 was administered to participants with advanced TNBC at the maximum tolerated dose (MTD) identified from Module 1A (360 mg once daily [OD]).

Reporting group title

Module 1 Part B-2 360mg OD (CRPC)

Reporting group description

In this Module 1B-2, CT7001 was administered to participants with advanced CRPC at the maximum tolerated dose (MTD) identified from Module 1A (360 mg once daily [OD]).

Reporting group title

Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)

Reporting group description

Reporting group title

Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)

Reporting group description

Reporting group title

Module 4-120 mg OD

Reporting group description

Reporting group title

Module 4 360 mg OD

Reporting group description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Sequence 3: 360 mg CT7001 fed in Period 1 followed by 360 mg CT7001 fasted in Period 2. Sequence 4: 360 mg CT7001 fasted in Period 1 followed by 360 mg CT7001 fed in Period 2.

Reporting group values	Module 1 Part A-Cohort 1 120mg OD	Module 1 Part A-Cohort 2 240 mg OD	Module 1 Part A-Cohort 3 480 mg OD	Module 1 Part A-Cohort 4 360 mg OD	Module 1 Part A-Cohort 5 180 mg BID	Module 1 Part B-1 360mg OD (TNBC)	Module 1 Part B-2 360mg OD (CRPC)	Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)	Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)	Module 4-120 mg OD	Module 4 360 mg OD	Total
Number of subjects	6	12	6	12	8	23	11	6	25	8	7	124
Age categorical
Units: Subjects
In utero	0	0	0	0	0	0	0	0	0	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0	0	0	0	0	0	0	0	0	0
Newborns (0-27 days)	0	0	0	0	0	0	0	0	0	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0	0	0	0	0	0	0	0	0	0
Children (2-11 years)	0	0	0	0	0	0	0	0	0	0	0	0
Adolescents (12-17 years)	0	0	0	0	0	0	0	0	0	0	0	0
Adults (18-64 years)	5	7	6	7	4	19	5	5	15	3	3	79
From 65-84 years	1	5	0	5	4	4	6	1	10	5	4	45
85 years and over	0	0	0	0	0	0	0	0	0	0	0	0
Gender categorical
Units: Subjects
Female	4	7	6	9	6	23	0	6	25	2	3	91
Male	2	5	0	3	2	0	11	0	0	6	4	33

End points

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Reporting group title

Module 1 Part A-Cohort 1 120mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 2 240 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 3 480 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 4 360 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 5 180 mg BID

Reporting group description

Reporting group title

Module 1 Part B-1 360mg OD (TNBC)

Reporting group description

In this Module 1B-1, CT7001 was administered to participants with advanced TNBC at the maximum tolerated dose (MTD) identified from Module 1A (360 mg once daily [OD]).

Reporting group title

Module 1 Part B-2 360mg OD (CRPC)

Reporting group description

In this Module 1B-2, CT7001 was administered to participants with advanced CRPC at the maximum tolerated dose (MTD) identified from Module 1A (360 mg once daily [OD]).

Reporting group title

Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)

Reporting group description

Reporting group title

Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)

Reporting group description

Reporting group title

Module 4-120 mg OD

Reporting group description

Reporting group title

Module 4 360 mg OD

Reporting group description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Sequence 3: 360 mg CT7001 fed in Period 1 followed by 360 mg CT7001 fasted in Period 2. Sequence 4: 360 mg CT7001 fasted in Period 1 followed by 360 mg CT7001 fed in Period 2.

Subject analysis set title

Module 4-120 mg OD Fed - fasted (Sequence 1)

Subject analysis set type

Per protocol

Subject analysis set description

Subject analysis set title

Module 4 120 mg OD Fasted-Fed (Sequence 2)

Subject analysis set type

Per protocol

Subject analysis set description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Sequence 2: 120 mg CT7001 fasted in Period 1 followed by 120 mg CT7001 fed in Period 2

Subject analysis set title

Module 4 360 mg OD Fed - fasted (Sequence 3)

Subject analysis set type

Per protocol

Subject analysis set description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Sequence 3: 360 mg CT7001 fed in Period 1 followed by 360 mg CT7001 fasted in Period 2.

Subject analysis set title

Module 4 360 mg OD Fasted- fed (Sequence 4)

Subject analysis set type

Per protocol

Subject analysis set description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Sequence 4: 360 mg CT7001 fasted in Period 1 followed by 360 mg CT7001 fed in Period 2.

Primary: Number of participants with one or more Treatment Emergent Adverse Events (TEAEs)

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End point title

Number of participants with one or more Treatment Emergent Adverse Events (TEAEs) ^[1]

End point description

Adverse events were recorded for each participant with causality (relationship or otherwise to study treatment) assessed by investigator. Treatment-emergent adverse events (TEAEs) are defined as those AEs which occur from Cycle 0 Day 1/Cycle 1 Day 1 of the study module to 28 days after the last dose of CT7001 in a module. Adverse events termed "related" are those assessed by the investigator as possibly related, probably related, or related to CT7001.

End point type

Primary

End point timeframe

From first dose of study drug to participant (for non-serious AEs) or provision of informed consent (serious AEs [SAEs]) until the end of study visit (28 - 35 days after last dose of study drug).

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical analysis were carried out. All data were summarized using standard summary statistics and were descriptive in nature.

End point values	Module 1 Part A-Cohort 1 120mg OD	Module 1 Part A-Cohort 2 240 mg OD	Module 1 Part A-Cohort 3 480 mg OD	Module 1 Part A-Cohort 4 360 mg OD	Module 1 Part A-Cohort 5 180 mg BID	Module 1 Part B-1 360mg OD (TNBC)	Module 1 Part B-2 360mg OD (CRPC)	Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)	Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)	Module 4-120 mg OD	Module 4 360 mg OD
Number of subjects analysed	6	12	6	12	8	23	11	6 ^[2]	25 ^[3]	8 ^[4]	7 ^[5]
Units: Participants
Participants with one or more TEAE	6	12	6	12	8	23	11	6	25	8	7
Participants with one or more related TEAEs	6	12	6	12	8	22	11	6	24	8	7

Notes
[2] - AEs were assessed in relation to CT7001 and Fulvestrant. Data shown describes AEs related to CT7001.
[3] - AEs were assessed in relation to CT7001 and Fulvestrant. Data shown describes AEs related to CT7001.
[4] - Results reported for the entire study period (crossover phase and continuous dosing phase combined)
[5] - Results reported for the entire study period (crossover phase and continuous dosing phase combined)

No statistical analyses for this end point

Primary: Number of participants with Serious adverse events (SAEs)

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End point title

Number of participants with Serious adverse events (SAEs) ^[6]

End point description

Serious adverse events (SAEs) are defined as any untoward medical occurrence that results in death, hospitalisation or prolongation of existing hospitalisation, persistent or significant disability/incapacity or a congenital anomaly or birth defect. Adverse events are classed as "related" if the event was assessed by investigator as probably related, possibly related, or related to CT7001 treatment.

End point type

Primary

End point timeframe

Provision of informed consent until 28 days after last dose of study drug

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical analysis were carried out. All data were summarized using standard summary statistics and were descriptive in nature.

End point values	Module 1 Part A-Cohort 1 120mg OD	Module 1 Part A-Cohort 2 240 mg OD	Module 1 Part A-Cohort 3 480 mg OD	Module 1 Part A-Cohort 4 360 mg OD	Module 1 Part A-Cohort 5 180 mg BID	Module 1 Part B-1 360mg OD (TNBC)	Module 1 Part B-2 360mg OD (CRPC)	Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)	Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)	Module 4-120 mg OD	Module 4 360 mg OD
Number of subjects analysed	6	12	6	12	8	23	11	6	25	8 ^[7]	7 ^[8]
Units: Participants
Number of participants experiencing SAE	1	4	1	3	3	9	2	2	8	0	4
Number of SAEs related to CT7001	0	0	0	0	0	4	0	1	1	0	1
Number of SAEs not related to CT7001	1	4	1	5	3	15	2	1	7	0	4

Notes
[7] - Results reported for the entire study period (crossover phase and continuous dosing phase combined)
[8] - Results reported for the entire study period (crossover phase and continuous dosing phase combined)

No statistical analyses for this end point

Primary: Incidence of Grade 3 or higher AEs reported in >1 participant

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End point title

Incidence of Grade 3 or higher AEs reported in >1 participant ^[9]

End point description

Adverse events (AEs) were collected throughout the study and assigned grades by the investigator: Grade 1 (mild AE), Grade 2 (moderate), Grade 3 (severe), Grade 4 (life threatening) or Grade 5 (fatal). This data describes the number of participants who experienced one or more AEs assessed as maximum Grade 3, 4 or 5.

End point type

Primary

End point timeframe

From first dose of study drug to participant (for non-serious AEs) or provision of informed consent (serious AEs [SAEs]) until the end of study visit (28 - 35 days after last dose of study drug).

Notes
[9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical analysis were carried out. All data were summarized using standard summary statistics and were descriptive in nature.

End point values	Module 1 Part A-Cohort 1 120mg OD	Module 1 Part A-Cohort 2 240 mg OD	Module 1 Part A-Cohort 3 480 mg OD	Module 1 Part A-Cohort 4 360 mg OD	Module 1 Part A-Cohort 5 180 mg BID	Module 1 Part B-1 360mg OD (TNBC)	Module 1 Part B-2 360mg OD (CRPC)	Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)	Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)	Module 4-120 mg OD	Module 4 360 mg OD
Number of subjects analysed	6	12	6	12	8	23	11	6	25	8 ^[10]	7 ^[11]
Units: Participants
Participants with any Grade 3 or higher AE	2	6	4	6	3	10	11	4	17	1	4

Notes
[10] - Results reported for the entire study period (crossover phase and continuous dosing phase combined)
[11] - Results reported for the entire study period (crossover phase and continuous dosing phase combined)

No statistical analyses for this end point

Primary: Best Objective Response (BOR) following study treatment (Module 1 Part B-2 only)

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End point title

Best Objective Response (BOR) following study treatment (Module 1 Part B-2 only) ^[12] ^[13]

End point description

At each tumor assessment visit, participants were assigned tumor responses of complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD) by the investigator according to RECIST (Response Evaluation Criteria in Solid Tumours) V1.1. The best objective response (BOR) was determined for each participant based on the best response recorded from the start of study treatment to the end of treatment, including any assessments for confirmation after the end of treatment. CR defined as disappearance of all target lesions; PR as at least a 30% decrease in the sum of diameters of target lesions; PD as at least a 20% increase in the sum of diameters of target lesions; SD as neither sufficient shrinkage to quality for PR, nor sufficient increase to qualify for PD.

End point type

Primary

End point timeframe

Start of study treatment to end of treatment (including any assessments for confirmation after the end of treatment)

Notes
[12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical analysis were carried out. All data were summarized using standard summary statistics and were descriptive in nature.
[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: Results reported as this was the primary endpoint for Module 1 Part B-2 only based on the primary objective.

End point values	Module 1 Part B-2 360mg OD (CRPC)
Number of subjects analysed	11
Units: Participants
Complete response (CR)	0
Partial response (PR)	0
Stable disease (SD)	5
Progressive disease (PD)	5
Not evaluable	1

No statistical analyses for this end point

Primary: Maximum observed plasma concentration (Cmax) of CT7001 (Module 4 only)

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End point title

Maximum observed plasma concentration (Cmax) of CT7001 (Module 4 only) ^[14]

End point description

Cmax is the maximum observed plasma concentration of CT7001 following oral dosing. The primary objective specific to Module 4 was to evaluate the effect of food on total and peak exposure of CT7001 when dosed as a capsule formulation to patients with advanced solid malignancies. Participants received either 120 mg (Cohort 1) or 360 mg (Cohort 2) of CT7001 as a single dose in the fed state in Period 1 and another single dose in the fed state in Period 2, or vice versa. The two doses were separated by a washout period of 7 days. After participants completed the single dose fed/fasted crossover phase, they continued into the continuous dosing phase of the module (Period 2 Day 8 of the crossover phase = Cycle 1 Day 1 of the continuous dosing phase) which continued until disease progression, death, prohibitive toxicity, or withdrawal of consent by participant.

End point type

Primary

End point timeframe

Pre-dose Cycle 0 Day 1 to 24 hours post-dose Cycle 2 Day 1 (before Cycle 2 Day 2 dose)

Notes
[14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical analysis were carried out. All data were summarized using standard summary statistics and were descriptive in nature.

End point values	Module 4-120 mg OD Fed - fasted (Sequence 1)	Module 4 120 mg OD Fasted-Fed (Sequence 2)	Module 4 360 mg OD Fed - fasted (Sequence 3)	Module 4 360 mg OD Fasted- fed (Sequence 4)
Number of subjects analysed	6	8	6	4
Units: ng/mL
geometric mean (full range (min-max))
Cmax	19.21 (3.41 to 53.1)	63.77 (14.4 to 238)	138.8 (113 to 195)	176.1 (52.6 to 302)

No statistical analyses for this end point

Primary: Area under the plasma concentration-time curve (AUC) 0-∞ (Module 4 only)

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End point title

Area under the plasma concentration-time curve (AUC) 0-∞ (Module 4 only) ^[15]

End point description

Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC 0-∞) was used in the evaluation of the effect of food on the total and peak exposure of CT7001 (where AUC0-∞ could not be calculated, AUC 0-72 hours was used in the evaluation). Participants received either 120 mg (Cohort 1) or 360 mg (Cohort 2) of CT7001 as a single dose in the fed state in Period 1 and another single dose in the fed state in Period 2, or vice versa. The two doses were separated by a washout period of 7 days. After participants completed the single dose fed/fasted crossover phase, they continued into the continuous dosing phase of the module (Period 2 Day 8 of the crossover phase = Cycle 1 Day 1 of the continuous dosing phase) which continued until disease progression, death, prohibitive toxicity, or withdrawal of consent.

End point type

Primary

End point timeframe

Pre-dose to 168 hours following oral administration of single dose of CT7001

Notes
[15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No formal statistical analysis were carried out. All data were summarized using standard summary statistics and were descriptive in nature.

End point values	Module 4-120 mg OD Fed - fasted (Sequence 1)	Module 4 120 mg OD Fasted-Fed (Sequence 2)	Module 4 360 mg OD Fed - fasted (Sequence 3)	Module 4 360 mg OD Fasted- fed (Sequence 4)
Number of subjects analysed	3 ^[16]	7 ^[17]	5 ^[18]	7
Units: h.ng/ml
geometric mean (full range (min-max))	785.3 (719 to 925)	694.9 (294 to 1470)	2696 (1500 to 3710)	2545 (766 to 4760)

Notes
[16] - Only 3 participants contributed to AUC0-∞ in fed state
[17] - Only 7 participants contributed to AUC0-∞ in fasted state
[18] - Only 5 participants contributed to AUC0-∞ in fed state

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

SAEs were continuously monitored throughout the study from signing of the ICF through to the end of study visit. AEs (non-serious) were recorded from the time the participant had taken at least 1 dose of IMP through to the participant’s last visit.

Adverse event reporting additional description

AEs and TEAEs from all cycles of treatment were presented graphically, as deemed appropriate. These were summarized by MedDRA system organ class (SOC), preferred term (PT), and Common Terminology Criteria for Adverse Events (CTCAE) grade. Serious adverse events (SAEs) were analyzed and reported separately.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

Module 1 Part A-Cohort 1 120mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 2 240 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 3 480 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 4 360 mg OD

Reporting group description

Reporting group title

Module 1 Part A-Cohort 5 180 mg BID

Reporting group description

Reporting group title

Module 1 Part B-1 360mg OD (TNBC)

Reporting group description

In this Module 1B-1, CT7001 was administered to participants with advanced TNBC at the maximum tolerated dose (MTD) identified from Module 1A (360 mg once daily [OD]).

Reporting group title

Module 1 Part B-2 360mg OD (CRPC)

Reporting group description

In this Module 1B-2, CT7001 was administered to participants with advanced CRPC at the maximum tolerated dose (MTD) identified from Module 1A (360 mg once daily [OD]).

Reporting group title

Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)

Reporting group description

Reporting group title

Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)

Reporting group description

Reporting group title

Module 4-120 mg OD

Reporting group description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Participants treated with 120 mg CT7001 OD in this cohort.

Reporting group title

Module 4 360 mg OD

Reporting group description

Module 4 evaluated the effect of food on the PK of CT7001 using a randomized, balanced, single-dose, two-treatment (fed vs. fasting), two-period, two-sequence crossover design, followed by a continuous treatment phase. Participants treated with 360 mg CT7001 OD in this cohort.

Serious adverse events	Module 1 Part A-Cohort 1 120mg OD	Module 1 Part A-Cohort 2 240 mg OD	Module 1 Part A-Cohort 3 480 mg OD	Module 1 Part A-Cohort 4 360 mg OD	Module 1 Part A-Cohort 5 180 mg BID	Module 1 Part B-1 360mg OD (TNBC)	Module 1 Part B-2 360mg OD (CRPC)	Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)	Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)	Module 4-120 mg OD	Module 4 360 mg OD
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 6 (16.67%)	4 / 12 (33.33%)	1 / 6 (16.67%)	3 / 12 (25.00%)	3 / 8 (37.50%)	9 / 23 (39.13%)	2 / 11 (18.18%)	2 / 6 (33.33%)	8 / 25 (32.00%)	0 / 8 (0.00%)	4 / 7 (57.14%)
number of deaths (all causes)	1	1	0	0	0	2	0	0	1	0	1
number of deaths resulting from adverse events	1	1	0	0	0	2	0	0	1	0	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant neoplasm progression
subjects affected / exposed	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to central nervous system
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lung neoplasm malignant
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypotension
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Disease progression
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Lung disorder
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diaphragm muscle weakness
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea at rest
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypoxia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleural effusion
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular graft occlusion
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Atrial flutter
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Presyncope
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebrovascular accident
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cerebral haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Posterior reversible encephalopathy syndrome
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Eye disorders
Retinal detachment
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	2 / 23 (8.70%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	1 / 2	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroesophageal reflux disease
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Large intestine perforation
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diaphragmatic hernia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intra-abdominal haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	2 / 7 (28.57%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Liver injury
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skin infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Atypical pneumonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
COVID-19 pneumonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acidosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypercalcaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 1%

Non-serious adverse events	Module 1 Part A-Cohort 1 120mg OD	Module 1 Part A-Cohort 2 240 mg OD	Module 1 Part A-Cohort 3 480 mg OD	Module 1 Part A-Cohort 4 360 mg OD	Module 1 Part A-Cohort 5 180 mg BID	Module 1 Part B-1 360mg OD (TNBC)	Module 1 Part B-2 360mg OD (CRPC)	Module 2 Part A CT7001 240 mg OD + fulvestrant (Cohort 1)	Module 2 Part A CT7001 360 mg OD + fulvestrant (Cohort 2)	Module 4-120 mg OD	Module 4 360 mg OD
Total subjects affected by non serious adverse events
subjects affected / exposed	6 / 6 (100.00%)	12 / 12 (100.00%)	6 / 6 (100.00%)	12 / 12 (100.00%)	8 / 8 (100.00%)	23 / 23 (100.00%)	11 / 11 (100.00%)	6 / 6 (100.00%)	25 / 25 (100.00%)	8 / 8 (100.00%)	7 / 7 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	0	0	1	0	0	0
Tumour pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Breast cancer
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Vascular disorders
Hot flush
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	2	1	0	0	2	1	0	0
Hypertension
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Haematoma
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0
Hypotension
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Lymphoedema
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Flushing
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Surgical and medical procedures
Chest tube insertion
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Tooth repair
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
General disorders and administration site conditions
Mucosal inflammation
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	2	0	2	0	0	5	0	0
Fatigue
subjects affected / exposed	2 / 6 (33.33%)	7 / 12 (58.33%)	0 / 6 (0.00%)	6 / 12 (50.00%)	2 / 8 (25.00%)	11 / 23 (47.83%)	2 / 11 (18.18%)	2 / 6 (33.33%)	8 / 25 (32.00%)	6 / 8 (75.00%)	2 / 7 (28.57%)
occurrences all number	2	7	0	10	3	13	2	4	14	8	2
Crepitations
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	1	1	0
Oedema peripheral
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	1	0	0	3	0	0	0	0
Pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	2	0	0
Biliary tract infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Asthenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
Chills
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	2	0	0
Influenza like illness
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	1
Infusion site extravasation
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Injection site bruising
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Pyrexia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Disease progression
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Facial pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Immune system disorders
Seasonal allergy
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Prothrombin time prolonged
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Hypersensitivity
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Reproductive system and breast disorders
Menometrorrhagia
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Breast pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	1	0	0
Vulvovaginal pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	0
Breast discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Nipple exudate bloody
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Pelvic pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	2	0	0	0
Priapism
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
subjects affected / exposed	5 / 6 (83.33%)	1 / 12 (8.33%)	0 / 6 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	2 / 23 (8.70%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)
occurrences all number	5	1	0	2	1	3	1	0	0	3	0
Cough
subjects affected / exposed	1 / 6 (16.67%)	4 / 12 (33.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	3 / 8 (37.50%)	3 / 23 (13.04%)	2 / 11 (18.18%)	2 / 6 (33.33%)	1 / 25 (4.00%)	3 / 8 (37.50%)	1 / 7 (14.29%)
occurrences all number	3	4	0	0	3	3	2	2	2	3	1
Dyspnoea
subjects affected / exposed	2 / 6 (33.33%)	1 / 12 (8.33%)	1 / 6 (16.67%)	2 / 12 (16.67%)	0 / 8 (0.00%)	2 / 23 (8.70%)	2 / 11 (18.18%)	2 / 6 (33.33%)	3 / 25 (12.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	2	1	2	2	0	2	4	2	4	1	0
Pleural effusion
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	1	0	2	0	0	0	0	0
Epistaxis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	3	1	0	0	3	0	0
Oropharyngeal pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	3	0	0	2	0	0	0
Pulmonary embolism
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Dyspnoea exertional
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	1	0	0	0	0	0
Increased viscosity of upper respiratory secretion
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Rhinalgia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Hypoxia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Dyspnoea at rest
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Haemoptysis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Productive cough
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	3
Rhinorrhoea
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	3 / 25 (12.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	3	0	0
Anxiety
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	3 / 25 (12.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	3	0	0
Depressed mood
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Disorientation
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Emotional distress
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Investigations
Electrocardiogram QT prolonged
subjects affected / exposed	1 / 6 (16.67%)	2 / 12 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	2	0	2	0	0	3	0	1	0	0
Blood creatine increased
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	1	0	2	0	0	2	0	0	0	1
Aspartate aminotransferase increased
subjects affected / exposed	1 / 6 (16.67%)	1 / 12 (8.33%)	2 / 6 (33.33%)	2 / 12 (16.67%)	1 / 8 (12.50%)	1 / 23 (4.35%)	2 / 11 (18.18%)	5 / 6 (83.33%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	2	1	3	2	1	1	3	5	0	0	1
Alanine aminotransferase increased
subjects affected / exposed	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 6 (16.67%)	4 / 12 (33.33%)	1 / 8 (12.50%)	1 / 23 (4.35%)	2 / 11 (18.18%)	2 / 6 (33.33%)	5 / 25 (20.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	1	1	4	1	1	3	4	11	0	1
Neutrophil count decreased
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 23 (4.35%)	1 / 11 (9.09%)	1 / 6 (16.67%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	4	0	1	0	2	1	2	3	0	0
White blood cell count decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	1	0	0
Weight decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	2 / 8 (25.00%)	0 / 23 (0.00%)	2 / 11 (18.18%)	0 / 6 (0.00%)	5 / 25 (20.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	2	2	0	2	0	5	2	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	2	0	1	0	1	1	0	0
Hyperphosphataemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Lymph node palpable
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Blood glucose increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0
Body temperature increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	0	0	0
Blood magnesium decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Lymphocyte count decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Oxygen saturation decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Reticulocyte count increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Platelet count decreased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	2 / 11 (18.18%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	4	3	0	0	1	0
Blood urea increased
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Blood creatine phosphokinase increased
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	2	0	0	0	1	0	0	0	0	1
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	2 / 6 (33.33%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	1	1	1	0	0
Clavicle fracture
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	3	0	0	0	1	0	0
Multiple fractures
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Burn oral cavity
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Thermal burn
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Sunburn
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Humerus fracture
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Wound complication
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Rib fracture
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	1
Sinus bradycardia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	2	0	0
Atrioventricular block first degree
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0
Pericardial effusion
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Atrial fibrillation
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0
Cardiac failure
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0
Atrial flutter
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Nervous system disorders
Neuralgia
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	1	0	0	0	0	0
Dysgeusia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	1 / 11 (9.09%)	0 / 6 (0.00%)	4 / 25 (16.00%)	2 / 8 (25.00%)	1 / 7 (14.29%)
occurrences all number	0	1	0	0	0	3	2	0	4	2	1
Paraesthesia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	1	0	0	0	2	1	0	0
Headache
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 6 (33.33%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	4 / 6 (66.67%)	4 / 25 (16.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	2	1	2	0	0	17	6	2	0
Dizziness
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	4 / 25 (16.00%)	2 / 8 (25.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	2	1	0	0	1	5	2	1
Intention tremor
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Nystagmus
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Presyncope
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Ageusia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	1	0
Dyskinesia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0
Electric shock sensation
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Lethargy
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	1	0	1	0	0
Neuropathy peripheral
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	1	0
Peripheral motor neuropathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Peripheral sensory neuropathy
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Sciatica
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Syncope
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Taste disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	4 / 25 (16.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	4	0	0
Tremor
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0
Depression
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
Circadian rhythm sleep disorder
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Cluster headache
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Dysarthria
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Spinal cord compression
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 6 (16.67%)	5 / 12 (41.67%)	1 / 6 (16.67%)	2 / 12 (16.67%)	1 / 8 (12.50%)	1 / 23 (4.35%)	3 / 11 (27.27%)	1 / 6 (16.67%)	3 / 25 (12.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	5	7	1	2	2	1	4	1	12	0	1
Lymphadenopathy
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Thrombocytopenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	1 / 8 (12.50%)	1 / 23 (4.35%)	4 / 11 (36.36%)	0 / 6 (0.00%)	4 / 25 (16.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	5	5	4	5	0	6	0	0
Leukopenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	5	0	0
Lymphopenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	6	0	0
Neutropenia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0
Ear and labyrinth disorders
Hypoacusis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	0	0	0
Eye disorders
Diplopia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Dry eye
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Vision blurred
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	2	0	0
Visual impairment
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	1
Vitreous floaters
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Eye discharge
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Eye pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	6 / 6 (100.00%)	8 / 12 (66.67%)	5 / 6 (83.33%)	12 / 12 (100.00%)	6 / 8 (75.00%)	21 / 23 (91.30%)	10 / 11 (90.91%)	5 / 6 (83.33%)	23 / 25 (92.00%)	7 / 8 (87.50%)	6 / 7 (85.71%)
occurrences all number	10	11	15	27	13	67	16	14	72	17	13
Dyspepsia
subjects affected / exposed	1 / 6 (16.67%)	2 / 12 (16.67%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	2	0	1	0	0	0	0	2	0	0
Vomiting
subjects affected / exposed	4 / 6 (66.67%)	8 / 12 (66.67%)	5 / 6 (83.33%)	10 / 12 (83.33%)	7 / 8 (87.50%)	14 / 23 (60.87%)	6 / 11 (54.55%)	6 / 6 (100.00%)	17 / 25 (68.00%)	5 / 8 (62.50%)	4 / 7 (57.14%)
occurrences all number	8	30	17	15	10	32	9	8	49	13	9
Nausea
subjects affected / exposed	5 / 6 (83.33%)	9 / 12 (75.00%)	3 / 6 (50.00%)	11 / 12 (91.67%)	6 / 8 (75.00%)	22 / 23 (95.65%)	8 / 11 (72.73%)	6 / 6 (100.00%)	19 / 25 (76.00%)	7 / 8 (87.50%)	5 / 7 (71.43%)
occurrences all number	7	10	5	20	9	40	13	15	40	11	15
Abdominal pain
subjects affected / exposed	3 / 6 (50.00%)	1 / 12 (8.33%)	2 / 6 (33.33%)	5 / 12 (41.67%)	1 / 8 (12.50%)	6 / 23 (26.09%)	2 / 11 (18.18%)	2 / 6 (33.33%)	7 / 25 (28.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)
occurrences all number	3	1	2	6	1	7	2	2	10	1	1
Constipation
subjects affected / exposed	0 / 6 (0.00%)	3 / 12 (25.00%)	0 / 6 (0.00%)	4 / 12 (33.33%)	0 / 8 (0.00%)	7 / 23 (30.43%)	2 / 11 (18.18%)	2 / 6 (33.33%)	6 / 25 (24.00%)	4 / 8 (50.00%)	2 / 7 (28.57%)
occurrences all number	0	3	0	6	0	9	2	3	8	5	3
Abdominal pain upper
subjects affected / exposed	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 12 (0.00%)	1 / 8 (12.50%)	2 / 23 (8.70%)	1 / 11 (9.09%)	2 / 6 (33.33%)	6 / 25 (24.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	1	1	1	0	2	2	1	2	7	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	2	3	0	0	0	2	0	0
Dry mouth
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	1 / 23 (4.35%)	1 / 11 (9.09%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	1	1	1	1	0	2	0	0
Dysphagia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	4 / 25 (16.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	5	0	0
Abdominal discomfort
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	2	0	0	0	0	0	0	0
Mouth ulceration
subjects affected / exposed	1 / 6 (16.67%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	1	0	1	0	0	0	2	0	0
Hypoaesthesia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	2	0	0	0	0	0
Oral pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	1	1	0	0	0	0	0
Inguinal hernia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Epigastric discomfort
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Irritable bowel syndrome
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Gastritis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Rectal haemorrhage
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	1	1	0	0	0	0	0
Abdominal pain lower
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	2 / 8 (25.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	0	0	0
Abdominal distension
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)
occurrences all number	0	0	0	1	0	0	1	0	1	1	1
Lip ulceration
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Toothache
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	1
Faeces pale
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Retching
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0
Stomatitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	3 / 23 (13.04%)	0 / 11 (0.00%)	2 / 6 (33.33%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	3	0	0	8	0	2	2	0	0
Diaphragmatic hernia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Flatulence
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	1	0
Frequent bowel movements
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Gingival pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Glossitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	3	0	0
Haematochezia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Lip blister
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Lip dry
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	2	0	0
Paraesthesia oral
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0
Cheilitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Proctalgia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Duodenogastric reflux
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
Dental caries
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Hyperaesthesia teeth
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Hypoaesthesia oral
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Lip pruritus
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Hepatobiliary disorders
Jaundice
subjects affected / exposed	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0	0
Hypertransaminasaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Liver injury
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 23 (4.35%)	1 / 11 (9.09%)	1 / 6 (16.67%)	5 / 25 (20.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	1	2	1	2	5	0	1
Skin exfoliation
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	2	0	0
Dry skin
subjects affected / exposed	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	2 / 25 (8.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)
occurrences all number	0	2	0	0	0	0	0	1	2	1	1
Pruritus
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)
occurrences all number	0	0	0	2	0	0	0	0	1	1	1
Dermatitis contact
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0
Alopecia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	1	0	0	2	0	0	2	0	0
Blister
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Rash maculo-papular
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	1	0	2	0	0	0	1	0	1	0
Rash pruritic
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1
Skin ulcer
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Eczema
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Palmar-plantar erythrodysaesthesia syndrome
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Skin mass
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	2 / 8 (25.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	2	0
Rash erythematous
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Hyperhidrosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Renal and urinary disorders
Urinary incontinence
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Acute kidney injury
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Dysuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0
Haematuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	3 / 11 (27.27%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	1	0	0
Pollakiuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Proteinuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Urinary tract obstruction
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Chronic kidney disease
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2
Glycosuria
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	2 / 6 (33.33%)	2 / 12 (16.67%)	0 / 6 (0.00%)	2 / 12 (16.67%)	0 / 8 (0.00%)	1 / 23 (4.35%)	1 / 11 (9.09%)	2 / 6 (33.33%)	0 / 25 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)
occurrences all number	2	2	0	2	0	1	1	3	0	1	1
Musculoskeletal chest pain
subjects affected / exposed	1 / 6 (16.67%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	1	0	0	0	2	1	0	1	0	0
Pain in extremity
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	1 / 11 (9.09%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	2	1	0	4	0	0
Chest pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	2	0	0	0	4	0	0	0	0	0
Groin pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	2	0	0	0	0	0	1	0	0	0
Bone pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	2	0	0
Arthralgia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	2 / 11 (18.18%)	1 / 6 (16.67%)	3 / 25 (12.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	2	1	0	0	1	2	3	8	0	1
Musculoskeletal pain
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	2 / 8 (25.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	1	0	1	2	0	0	1	1	1	0
Muscle spasms
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	2	0	0
Joint swelling
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Flank pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0
Muscular weakness
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	1 / 11 (9.09%)	2 / 6 (33.33%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	1	2	1	0	0
Myalgia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1
Neck pain
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	1	0
Musculoskeletal discomfort
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0
Pain in jaw
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 6 (16.67%)	1 / 12 (8.33%)	2 / 8 (25.00%)	1 / 23 (4.35%)	1 / 11 (9.09%)	0 / 6 (0.00%)	3 / 25 (12.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	1	2	2	2	2	0	3	0	0
Bronchitis
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0
Fungal infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Tooth infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	2 / 8 (25.00%)	1 / 7 (14.29%)
occurrences all number	0	1	0	0	0	1	0	0	0	2	2
Liver function test abnormal
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Respiratory tract infection
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0
Liver abscess
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Biliary sepsis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Wound infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	2	0	0	0	0	0	0	0
Atypical pneumonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Candida infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
COVID-19
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	2	0	0
COVID-19 pneumonia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Cystitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Fungal skin infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Herpes zoster
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Laryngitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	2 / 6 (33.33%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	0
Rhinitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	1 / 6 (16.67%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	1	1	0	0
Sepsis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Vulvitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Vulvovaginal candidiasis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	0
Gingivitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Oral herpes
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	2	1	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	2 / 23 (8.70%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	2	0	0	0	0	0
Ear infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Labyrinthitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Nipple infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Oral candidiasis
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	1 / 23 (4.35%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	1	0	1	1	0	0	0	0
Skin infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Influenza
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	1	0
Device related infection
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	3	0
Pharyngitis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	1 / 23 (4.35%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	1 / 6 (16.67%)	2 / 12 (16.67%)	1 / 6 (16.67%)	3 / 12 (25.00%)	1 / 8 (12.50%)	3 / 23 (13.04%)	6 / 11 (54.55%)	2 / 6 (33.33%)	11 / 25 (44.00%)	3 / 8 (37.50%)	2 / 7 (28.57%)
occurrences all number	1	2	2	6	1	5	8	2	14	4	2
Dehydration
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	1 / 12 (8.33%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	3 / 25 (12.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	1	1	0	0	0	7	0	0
Hypocalcaemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	1 / 8 (12.50%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	4 / 25 (16.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	1	0	0	0	1	0	0	0	4	0	2
Hypoalbuminaemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	0
Hyperglycaemia
subjects affected / exposed	1 / 6 (16.67%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	2 / 11 (18.18%)	1 / 6 (16.67%)	4 / 25 (16.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	2	0	0	0	0	0	3	1	6	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	1	0	1	0	0
Cachexia
subjects affected / exposed	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	1	0
Acidosis
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Gout
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	1 / 25 (4.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0
Hypercalcaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	1 / 12 (8.33%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	1 / 6 (16.67%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	1	0	0	0	1	5	0	0
Hypokalaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	1 / 6 (16.67%)	5 / 25 (20.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	1	1	5	0	1
Hyponatraemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	4	0	0
Hypophosphataemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	3 / 11 (27.27%)	0 / 6 (0.00%)	2 / 25 (8.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	2	0	0
Diabetes mellitus inadequate control
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	1 / 11 (9.09%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0
Magnesium deficiency
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1
Diabetes mellitus
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	0 / 8 (0.00%)	1 / 7 (14.29%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Hypoglycaemia
subjects affected / exposed	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 6 (0.00%)	0 / 12 (0.00%)	0 / 8 (0.00%)	0 / 23 (0.00%)	0 / 11 (0.00%)	0 / 6 (0.00%)	0 / 25 (0.00%)	1 / 8 (12.50%)	0 / 7 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0

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Were there any global substantial amendments to the protocol? Yes

29 Sep 2017

Protocol Amendment Version 2.0, reason for amendment: • Further guidance on the MTD added • New exclusion criteria added to exclude patients who had received a live virus vaccination within 28 days of study entry • Additional rationale for the starting dose added and clarification added on the dose escalation scheme • Requirement for a pregnancy test changed from every other cycle to every cycle

28 Mar 2018

Protocol amendment Version 4.0, reason for amendment- •Clarified that if an increase in the daily dose was made this would not exceed the maximum total daily dose that had been explored and was tolerable •Requirement for a minimum of 7 days between completion of dosing in the first 21-day cycle in one cohort to the start of dosing in the subsequent cohort removed. •Clarification add as to what changes could be implemented following safety data review and agreement by the SRC, without the requirement to submit a substantial amendment to the IEC or the Regulatory Authorities. The frequency of PK sampling could also be modified based on SRC review and may include up to 3 additional PK samples of 4 mL each within any given cycle, to better characterize the individual PK profile based upon emerging PK data. Additionally, the following changes made in Version 3.0 (the protocol not implemented) were included in the Version 4.0: •Clarification of what changes could be implemented following review of the safety data by the SRC without the requirement to submit a substantial amendment •Clarification that the SRC could remove the requirement for participants to be dosed in a fasted state based on emerging pre-clinical and clinical data •Removal of the 7-day staggering interval for the second participant dosed in a cohort •PK sampling period extended to up to 168 hours and related changes to blood volumes collected •Exclusion criteria relating to prior receipt of a CDK inhibitor removed.

10 Jul 2018

Protocol amendment Version 5.0, reason for amendment- Updated details added on Module 4 to evaluate effect of food on the PK of CT7001 when given as monotherapy to participants with advanced solid malignancies (fed and fasting study).

25 Sep 2018

Protocol Amendment Version 6.0, reason for amendment •The protocol was separated out into a core protocol (Volume 1 and separate modules (Volumes 2 to 7) •Details added on Module 1B-1 (TNBC cohort) •All sections of the core protocol, including the introduction and background, were re-structured in the core protocol and updated to make it consistent with Module 1B-1 (TNBC).

06 Mar 2019

Protocol amendment Version 8.0, reason for amendment- •Wording for dose escalation in Module 2 updated to provide clarification that dose escalation must be stopped and a new substantial amendment approved if a lower dose or different dosing regimen was employed. •The Lead Biostatistician details were updated in the protocol approval signature page, along with updates to the Medical Monitor details and SAE reporting requirements. Note: Version 7.0 was not implemented ; Module 2 was removed from the main protocol and added as a separate module.

26 Mar 2019

Protocol amendment Version 9.0, reason for amendment- •Details added on Module 1B-2 (CRPC cohort) •Module 2 split into Parts A and B and details added on Part C •Introduction and background in the core protocol updated •MTD and preliminary recommended Phase 2 dose details updated •Contraception requirements updated to clarify contra-indication of some hormonal contraceptives in certain populations •Prohibited medications updated to permit participants with prostate cancer or pre/peri menopausal breast cancer to receive goserelin •Current PK/ PD, clinical and safety data updated as of 26 Nov 2018 and efficacy data updated as of per 24 Sep 2018.

30 Jan 2020

Protocol amendment Version 11.0, reason for amendment •Medical Monitor details changed to Pharmaceutical Product Development, LLC for Module 2 •Interactive web response system (IWRS) added to allocate CT7001 medication bottles to the participants •Requirement to interrupt or delay treatment due to Grade ≥4 thrombocytopenia changed to Grade ≥3 and platelet count level needed to restart treatment increased •Definition of an AESI added to the protocol, along with requirements for reporting AESIs •Overall risk/benefit assessment updated based on available non-clinical and clinical safety data as of 07 Jan 2020. The changes made in Version 10.0 (protocol not implemented) were also included in Version 11.0 •Introduction and background in the core protocol updated with latest PK/PD, clinical, efficacy data and modular status as per 10 Sep 2019 •Coagulation parameters removed from core laboratory tests •Timings of some exclusion criteria clarified •Fasting requirement for dosing removed as per SRC conclusion that food had no clinically relevant effect on the bioavailability of CT7001 •MTD and recommended Phase 2 dose of 360 mg OD taken forward to Module 4 Cohort 2, M1B-1 (TNBC and CRPC cohorts), and was also the target dose in Module 2. •Threshold for delayed dosing due to thrombocytopenia updated and level for dosing restart increased •Reference to goserelin removed and replaced with ‘LHRH agonist or, where applicable, surgical castration’ •Cannabinoids/cannabis oil added to the medications not recommended •Hair samples were added to the core biomarker analysis section and information for collection blood for CTCs and assessment of CYP and drug transporter genes added in section exploratory research.

27 Apr 2020

Protocol amendment Version 12.0, reason for amendment- The number of participants included in Module 1B-1 was increased to 30.

15 Jul 2020

Protocol amendment Version 13.0, reason for amendment •References to Module 1A solid tumor cohort have been deleted since this module was no longer being conducted •Introduction and background updated with latest clinical and efficacy data, as of 01 Jun 2020 •IWRS changed to IXRS •Exclusion criteria numbers 12 and 15 updated to clarify receipt of cytotoxic and small molecule IMP within 28 days or ≤ 5 half-lives, whichever is shorter, before the first dose of IMP •Anti-emetic guidance updated •IMP dose reduction, dose interruption or delay updated for Grade ≥ 3 anemia and treatment resumption on 240 mg OD after Grade ≥ 3 thrombocytopenia (platelet count < 50 x 109/L) added •New section added outlining the concurrent and palliative radiotherapy or surgeries that were permitted during the active treatment phase of the study •HbA1c added to the laboratory safety assessments and the requirement for a fasted glucose test added for participants with a medical history of diabetes •Requirement for blood samples for PBMCs to be used for Nanostring analyses removed from Module 1 Part B •Reference to collection of hair samples for biomarker analysis deleted •A new appendix was added to detail the sponsors actions and responses to the COVID-19 pandemic.

23 Dec 2020

Protocol Amendment Version 14.0, reason for amendment- •The international non-proprietary name of samuraciclib added •Details of Module 6 added and the MTD and recommended Phase 2 dose of 360 mg OD added throughout the module •Introduction and background updated with latest data as of 16 Nov 2020 •Permitted and/or recommended treatment provision of anti- emetic medication that should be given prophylactically for nausea and/or vomiting as indicated by the investigator and in accordance with the current DMC guidelines v1.0 dated 26 Oct 2020 •Nausea and vomiting guidelines added as an appendix

14 Jun 2021

Protocol amendment Version 15.0, reason for amendment • Introduction and background updated with latest clinical, safety and efficacy data as of 12 Apr 2021 • Definition of women not of child-bearing potential updated in inclusion criterion number 6 • Definition of a live virus updated • Changes made to permitted and recommended concomitant medications in the management of nausea, vomiting, and diarrhea. • Clarification and updates to live viruses and bacterial vaccines in prohibited medication • End of trial definition amended • Guidelines on the management of nausea, vomiting, and diarrhea updated to v2.0 dated 08 Jun 2021 • 360 mg OD confirmed as the starting dose for use in combination with fulvestrant in Module 2B.

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.

None reported

http://www.ncbi.nlm.nih.gov/pubmed/37488191

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Clinical trials

Clinical Trial Results:
A Modular, Multi-part, Multi-arm, Open-label, Phase I/IIa Study to Evaluate the Safety and Tolerability of CT7001 Alone and in Combination with Anti-cancer Treatments in Patients with Advanced Malignancies

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Primary: Number of participants with one or more Treatment Emergent Adverse Events (TEAEs)

Primary: Number of participants with one or more Treatment Emergent Adverse Events (TEAEs)

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Primary: Number of participants with Serious adverse events (SAEs)

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Primary: Incidence of Grade 3 or higher AEs reported in >1 participant

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Primary: Maximum observed plasma concentration (Cmax) of CT7001 (Module 4 only)

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Primary: Area under the plasma concentration-time curve (AUC) 0-∞ (Module 4 only)

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Clinical Trial Results: A Modular, Multi-part, Multi-arm, Open-label, Phase I/IIa Study to Evaluate the Safety and Tolerability of CT7001 Alone and in Combination with Anti-cancer Treatments in Patients with Advanced Malignancies

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Primary: Number of participants with one or more Treatment Emergent Adverse Events (TEAEs)

Primary: Number of participants with one or more Treatment Emergent Adverse Events (TEAEs)

Primary: Number of participants with Serious adverse events (SAEs)

Primary: Number of participants with Serious adverse events (SAEs)

Primary: Incidence of Grade 3 or higher AEs reported in >1 participant

Primary: Incidence of Grade 3 or higher AEs reported in >1 participant

Primary: Best Objective Response (BOR) following study treatment (Module 1 Part B-2 only)

Primary: Best Objective Response (BOR) following study treatment (Module 1 Part B-2 only)

Primary: Maximum observed plasma concentration (Cmax) of CT7001 (Module 4 only)

Primary: Maximum observed plasma concentration (Cmax) of CT7001 (Module 4 only)

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Primary: Area under the plasma concentration-time curve (AUC) 0-∞ (Module 4 only)

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Clinical Trial Results:
A Modular, Multi-part, Multi-arm, Open-label, Phase I/IIa Study to Evaluate the Safety and Tolerability of CT7001 Alone and in Combination with Anti-cancer Treatments in Patients with Advanced Malignancies