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Clinical Trial Results:
A PHASE 1/2 OPEN LABEL, MULTICENTER STUDY TO ASSESS THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND ANTI-TUMOR ACTIVITY OF ZN-C5 ALONE AND IN COMBINATION WITH PALBOCICLIB IN SUBJECTS WITH ESTROGEN-RECEPTOR POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR-2 NEGATIVE ADVANCED BREAST CANCER

Summary
EudraCT number	2018-001364-27
Trial protocol	CZ LT BG HU
Global end of trial date	22 Dec 2022

Results information
Results version number	v2(current)
This version publication date	29 Aug 2024
First version publication date	02 May 2024
Other versions	v1
Version creation reason	Correction of full data set Consistent with CT.gov posting.

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

ZN-c5-001

ISRCTN number

US NCT number

NCT03560531

WHO universal trial number (UTN)

Sponsor organisation name

Zeno Alpha Inc.

Sponsor organisation address

10275 Science Center Drive, Suite 200, San Diego, California, United States,

Public contact

Regulatory Head, Zeno Alpha, Inc., , +1 (858) 263-4333, RegLeads@zentalis.com

Scientific contact

Head of Regulatory, Zeno Alpha, Inc., , +1 (858) 263-4333, RegLeads@zentalis.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

22 Dec 2022

Is this the analysis of the primary completion data?

Yes

Primary completion date

26 Apr 2022

Global end of trial reached?

Yes

Global end of trial date

22 Dec 2022

Was the trial ended prematurely?

Main objective of the trial

Phase 1 • Monotherapy Dose Escalation: Determine a maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) for ZN-c5 as a monotherapy • Monotherapy Expansion: Investigate the safety and tolerability of ZN-c5 as a monotherapy in subjects with Estrogen Receptor (ER) positive, Human Epidermal Growth Factor Receptor-2 (HER2) negative advanced breast cancer • Combination Dose Escalation: Determine an MTD or RP2D for ZN-c5 when administered in combination with palbociclib Phase 2 • Monotherapy Phase 2: Determine preliminary anti-tumor efficacy [Clinical Benefit Rate (CBR)] for ZN-c5 as a monotherapy • Combination Phase 2: Determine preliminary anti-tumor efficacy (CBR) for ZN-c5 when administered in combination with palbociclib

Protection of trial subjects

This study was conducted in accordance with the ethical principles of Good Clinical Practice, according to the International Conference on Harmonization Guidelines.

Background therapy

Evidence for comparator

Actual start date of recruitment

30 Nov 2018

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 109

Country: Number of subjects enrolled

European Union: 72

Worldwide total number of subjects

181

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)

105

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study was initiated on 30 November 2018 and completed on 22 December 2022 (last participant last visit). 29 centers in Belarus, Bosnia and Herzegovina, the Czech Republic, Hungary, Lithuania, Russia, Serbia, Ukraine, and the United States enrolled the participants.

Screening details

Subjects received study drug once daily for 28-days cycle. At the same time some subjects could also receive the study drug twice daily. The study also has End-of-Treatment visit; 30 day safety follow up and disease assessment and long term follow up for every 12 weeks.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Non-randomised - controlled

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Phase 1 (Monotherapy): ZN-c5 50 mg QD

Arm description

Participants who received ZN-c5 50 mg once daily (QD) in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Phase 1 (Monotherapy): ZN-c5 75 mg QD

Arm description

Participants who received ZN-c5 75 mg QD in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Phase 1 (Monotherapy): ZN-c5 100 mg QD

Arm description

Participants who received ZN-c5 100 mg QD in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Phase 1 (Monotherapy): ZN-c5 75 mg BID

Arm description

Participants who received ZN-c5 75 mg twice daily (BID) in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Phase 1 (Monotherapy): ZN-c5 150 mg QD

Arm description

Participants who received ZN-c5 150 mg QD in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Phase 1 (Monotherapy): ZN-c5 150 mg BID

Arm description

Participants who received ZN-c5 150 mg BID in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Phase 1 (Monotherapy): ZN-c5 300 mg QD

Arm description

Participants who received ZN-c5 300 mg QD in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Phase 2 (Monotherapy): ZN-c5 50 mg QD

Arm description

Participants who received ZN-c5 50 mg QD in Phase 2 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Phase 1 (Combination Therapy): ZNc5 25mg QD + Palbociclib

Arm description

Participants who received ZN-c5 25 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Investigational medicinal product name

Palbociclib

Investigational medicinal product code

Other name

IBRANCE®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Palbociclib was dosed orally at 125 mg QD for 21 consecutive days, followed by 7 days off treatment to comprise a complete cycle of 28 days.

Phase 1 (Combination Therapy): ZNc5 25mg BID + Palbociclib

Arm description

Participants who received ZN-c5 25 mg BID along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Investigational medicinal product name

Palbociclib

Investigational medicinal product code

Other name

IBRANCE®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Palbociclib was dosed orally at 125 mg QD for 21 consecutive days, followed by 7 days off treatment to comprise a complete cycle of 28 days.

Phase 1 (Combination Therapy): ZNc5 50mg QD + Palbociclib

Arm description

Participants who received ZN-c5 50 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Investigational medicinal product name

Palbociclib

Investigational medicinal product code

Other name

IBRANCE®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Palbociclib was dosed orally at 125 mg QD for 21 consecutive days, followed by 7 days off treatment to comprise a complete cycle of 28 days.

Phase 1 (Combination Therapy): ZNc5 50mg BID + Palbociclib

Arm description

Participants who received ZN-c5 50 mg BID along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Investigational medicinal product name

Palbociclib

Investigational medicinal product code

Other name

IBRANCE®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Palbociclib was dosed orally at 125 mg QD for 21 consecutive days, followed by 7 days off treatment to comprise a complete cycle of 28 days.

Phase 1 (Combination Therapy): ZNc5 100mg QD + Palbociclib

Arm description

Participants who received ZN-c5 100 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Investigational medicinal product name

Palbociclib

Investigational medicinal product code

Other name

IBRANCE®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Palbociclib was dosed orally at 125 mg QD for 21 consecutive days, followed by 7 days off treatment to comprise a complete cycle of 28 days.

Phase 1 (Combination Therapy): ZNc5 150mg QD + Palbociclib

Arm description

Participants who received ZN-c5 150 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Arm type

Experimental

Investigational medicinal product name

ZN-c5

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Dose escalation cohorts are planned to determine MTD or RP2D of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Investigational medicinal product name

Palbociclib

Investigational medicinal product code

Other name

IBRANCE®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Palbociclib was dosed orally at 125 mg QD for 21 consecutive days, followed by 7 days off treatment to comprise a complete cycle of 28 days.

Number of subjects in period 1	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Combination Therapy): ZNc5 25mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 25mg BID + Palbociclib	Phase 1 (Combination Therapy): ZNc5 50mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 50mg BID + Palbociclib	Phase 1 (Combination Therapy): ZNc5 100mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 150mg QD + Palbociclib
Started	16	3	3	6	15	3	10	75	10	5	18	2	12	3
Completed	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Not completed	16	3	3	6	15	3	10	75	10	5	18	2	12	3
Study end per-protocol	1	1	2	-	1	-	-	-	-	-	-	-	-	-
Consent withdrawn by subject	1	-	-	-	-	-	-	3	2	-	-	-	2	-
Death	4	1	1	2	6	1	4	8	1	3	2	-	4	1
Early study termination by sponsor	9	-	-	4	8	2	5	64	7	2	16	2	6	2
Lost to follow-up	1	1	-	-	-	-	1	-	-	-	-	-	-	-

Baseline characteristics

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Reporting group title

Phase 1 (Monotherapy): ZN-c5 50 mg QD

Reporting group description

Participants who received ZN-c5 50 mg once daily (QD) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 75 mg QD

Reporting group description

Participants who received ZN-c5 75 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 100 mg QD

Reporting group description

Participants who received ZN-c5 100 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 75 mg BID

Reporting group description

Participants who received ZN-c5 75 mg twice daily (BID) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 150 mg QD

Reporting group description

Participants who received ZN-c5 150 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 150 mg BID

Reporting group description

Participants who received ZN-c5 150 mg BID in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 300 mg QD

Reporting group description

Participants who received ZN-c5 300 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 2 (Monotherapy): ZN-c5 50 mg QD

Reporting group description

Participants who received ZN-c5 50 mg QD in Phase 2 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 25mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 25 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 25mg BID + Palbociclib

Reporting group description

Participants who received ZN-c5 25 mg BID along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 50mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 50 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 50mg BID + Palbociclib

Reporting group description

Participants who received ZN-c5 50 mg BID along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 100mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 100 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 150mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 150 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Combination Therapy): ZNc5 25mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 25mg BID + Palbociclib	Phase 1 (Combination Therapy): ZNc5 50mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 50mg BID + Palbociclib	Phase 1 (Combination Therapy): ZNc5 100mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 150mg QD + Palbociclib	Total
Number of subjects	16	3	3	6	15	3	10	75	10	5	18	2	12	3	181
Age categorical
Units: Subjects
In utero	0	0	0	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	0	0	0
Newborns (0-27 days)	0	0	0	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	0	0	0
Children (2-11 years)	0	0	0	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	0	0	0
Adults (18-64 years)	11	3	3	3	10	2	5	39	6	3	8	2	8	2	105
From 65-84 years	5	0	0	3	5	1	4	35	4	2	10	0	4	1	74
85 years and over	0	0	0	0	0	0	1	1	0	0	0	0	0	0	2
Gender categorical
Units: Subjects
Female	16	3	3	6	15	3	10	75	10	5	18	2	11	3	180
Male	0	0	0	0	0	0	0	0	0	0	0	0	1	0	1
Race
Units: Subjects
American Indian or Alaska Native	0	0	0	0	0	0	0	0	0	0	0	1	0	0	1
Asian	2	0	0	1	0	0	0	0	0	0	0	0	0	0	3
Native Hawaiian or Other Pacific Islander	0	0	0	0	0	0	0	0	1	0	0	0	0	0	1
Black or African American	1	0	0	0	1	0	0	0	1	0	0	0	2	0	5
White	12	3	3	5	12	3	9	74	8	5	17	1	10	3	165
More than one race	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
Unknown or Not Reported	1	0	0	0	2	0	1	1	0	0	1	0	0	0	6
Region of Enrollment
Units: Subjects
United States	8	3	3	6	15	3	8	13	10	5	18	2	12	3	109
Europe	8	0	0	0	0	0	2	62	0	0	0	0	0	0	72

End points

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Reporting group title

Phase 1 (Monotherapy): ZN-c5 50 mg QD

Reporting group description

Participants who received ZN-c5 50 mg once daily (QD) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 75 mg QD

Reporting group description

Participants who received ZN-c5 75 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 100 mg QD

Reporting group description

Participants who received ZN-c5 100 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 75 mg BID

Reporting group description

Participants who received ZN-c5 75 mg twice daily (BID) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 150 mg QD

Reporting group description

Participants who received ZN-c5 150 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 150 mg BID

Reporting group description

Participants who received ZN-c5 150 mg BID in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 300 mg QD

Reporting group description

Participants who received ZN-c5 300 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 2 (Monotherapy): ZN-c5 50 mg QD

Reporting group description

Participants who received ZN-c5 50 mg QD in Phase 2 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 25mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 25 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 25mg BID + Palbociclib

Reporting group description

Participants who received ZN-c5 25 mg BID along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 50mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 50 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 50mg BID + Palbociclib

Reporting group description

Participants who received ZN-c5 50 mg BID along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 100mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 100 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 150mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 150 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Primary: Clinical Benefit Rate for ZN-c5 as a Monotherapy

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End point title

Clinical Benefit Rate for ZN-c5 as a Monotherapy ^[1] ^[2]

End point description

CBR is defined as the number of participants who have at least one confirmed response of complete response (CR) or partial response (PR) (only if participant has measurable disease), or stable disease (SD) >= 24 weeks (or non- CR/non-progressive disease (PD) >=24 weeks for participants with non-measurable disease) prior to any evidence of progression. Full Analysis Set consisted of all participants who received >=1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints.

End point type

Primary

End point timeframe

24 weeks

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistical analysis was performed for the primary end point.
[2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: Participants	7	0	1	1	4	1	5	38

No statistical analyses for this end point

Primary: Best Overall Response (BOR) for ZN-c5 as a Monotherapy

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End point title

Best Overall Response (BOR) for ZN-c5 as a Monotherapy ^[3] ^[4]

End point description

Best overall response was summarized categorically based on the four RECIST categories: CR, PR, SD and PD. Full Analysis Set consisted of all participants who received ≥1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints.

End point type

Primary

End point timeframe

24 Weeks

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Only descriptive statistical analysis was performed for the primary end point.
[4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: Participants
CR	0	0	0	0	0	0	0	0
PR	0	0	0	0	1	0	1	3
SD	13	1	1	6	10	3	7	50
SD ≥24 weeks	7	0	1	1	3	1	4	35
8 weeks < SD <24 weeks	6	1	0	5	7	2	3	15
PD	3	2	2	0	4	0	1	19
Non-Responders (NR)	0	0	0	0	0	0	1	3
Not Evaluable (NE)	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 2 Months

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End point title

Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 2 Months ^[5]

End point description

PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 2 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. The Tumor Response-Evaluable Set includes all participants in the full analysis set with at least 1 evaluable postbaseline response assessment using RECIST 1.1.

End point type

Secondary

End point timeframe

2 months

Notes
[5] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	9	72
Units: percentage of participants
number (confidence interval 95%)	87.1 (57.3 to 96.6)	66.7 (5.4 to 94.5)	33.3 (0.9 to 77.4)	100.0 (100.0 to 100.0)	73.3 (43.6 to 89.1)	100.0 (100.0 to 100.0)	87.5 (38.7 to 98.1)	77.8 (66.3 to 85.7)

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 4 Months

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End point title

Monotherapy Only: Percentage of Participants With Progression-Free Survival at 4 Months ^[6]

End point description

PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 4 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. The Tumor Response-Evaluable Set includes all participants in the full analysis set with at least 1 evaluable postbaseline response assessment using RECIST 1.1. Only participants with data collected at Month 4 are reported.

End point type

Secondary

End point timeframe

4 months

Notes
[6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	0 ^[7]	3	6	15	3	9	72
Units: percentage of participants
number (confidence interval 95%)	73.7 (44.1 to 89.2)	( to )	33.3 (0.9 to 77.4)	33.3 (4.6 to 67.6)	50.3 (22.6 to 72.8)	100.0 (100.0 to 100.0)	62.5 (22.9 to 86.1)	60.8 (48.5 to 71.0)

Notes
[7] - No participants analyzed.

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 6 Months

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End point title

Monotherapy Only: Percentage of Participants With Progression-Free Survival at 6 Months ^[8]

End point description

PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 6 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. The Tumor Response-Evaluable Set includes all participants in the full analysis set with at least 1 evaluable postbaseline response assessment using RECIST 1.1. Only participants with data collected at Month 6 are reported.

End point type

Secondary

End point timeframe

6 months

Notes
[8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	0 ^[9]	3	6	15	3	9	72
Units: percentage of participants
number (confidence interval 95%)	64.5 (33.6 to 83.8)	( to )	33.3 (0.9 to 77.4)	16.7 (0.8 to 51.7)	33.5 (10.8 to 58.4)	66.7 (5.4 to 94.5)	50.0 (15.2 to 77.5)	50.3 (38.1 to 61.3)

Notes
[9] - No participants analyzed.

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 8 Months

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End point title

Monotherapy Only: Percentage of Participants With Progression-Free Survival at 8 Months ^[10]

End point description

PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 8 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. The Tumor Response-Evaluable Set includes all participants in the full analysis set with at least 1 evaluable postbaseline response assessment using RECIST 1.1. Only participants with data collected at Month 8 are reported. -9999 and 9999= The 95% confidence internal data was not determined as no participants with PFS at Month 8.

End point type

Secondary

End point timeframe

8 months

Notes
[10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	0 ^[11]	3	6	15	3	9	72
Units: percentage of participants
number (confidence interval 95%)	64.5 (33.6 to 83.8)	( to )	0.0 (-9999 to 9999)	16.7 (0.8 to 51.7)	16.8 (2.7 to 41.2)	66.7 (5.4 to 94.5)	37.5 (8.7 to 67.4)	44.2 (32.3 to 55.5)

Notes
[11] - No participants analyzed.

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months

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End point title

Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months ^[12]

End point description

PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 10 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. The Tumor Response-Evaluable Set includes all participants in the full analysis set with at least 1 evaluable postbaseline response assessment using RECIST 1.1. Only participants with data collected at Month 10 are reported. -9999 and 9999= The 95% confidence internal data was not determined as no participants with PFS at Month 10.

End point type

Secondary

End point timeframe

10 months

Notes
[12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	0 ^[13]	3	6	15	3	9	72
Units: percentage of participants
number (confidence interval 95%)	55.2 (25.2 to 77.5)	( to )	0.0 (-9999 to 9999)	16.7 (0.8 to 51.7)	16.8 (2.7 to 41.2)	0.0 (-9999 to 9999)	12.5 (0.7 to 42.3)	35.9 (24.6 to 47.3)

Notes
[13] - No participants analyzed.

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 12 Months

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End point title

Monotherapy Only: Percentage of Participants With Progression-Free Survival at 12 Months ^[14]

End point description

PFS is defined as the time (in months) from the date of first dosing until the date of objective PD (as defined by RECIST version 1.1) or death (by any cause in the absence of progression), whichever occurs earlier. Kaplan-Meier estimates at 12 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. The Tumor Response-Evaluable Set includes all participants in the full analysis set with at least 1 evaluable postbaseline response assessment using RECIST 1.1. Only participants with data collected at Month 12 are reported. -9999 and 9999= The 95% confidence internal data was not determined as no participants with PFS at Month 12.

End point type

Secondary

End point timeframe

12 months

Notes
[14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	0 ^[15]	3	6	15	3	9	72
Units: percentage of participants
number (confidence interval 95%)	27.6 (6.9 to 53.9)	( to )	0.0 (-9999 to 9999)	16.7 (0.8 to 51.7)	16.8 (2.7 to 41.2)	0.0 (-9999 to 9999)	12.5 (0.7 to 42.3)	26.2 (15.8 to 37.8)

Notes
[15] - No participants analyzed.

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 2 Months

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End point title

Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 2 Months ^[16]

End point description

OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 2 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. Full Analysis Set consisted of all participants who received ≥1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints.

End point type

Secondary

End point timeframe

2 months

Notes
[16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: percentage of participants
number (confidence interval 95%)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	98.7 (90.9 to 99.8)

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 4 Months

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End point title

Monotherapy Only: Percentage of Participants With Overall Survival at 4 Months ^[17]

End point description

OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 4 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. Full Analysis Set consisted of all participants who received ≥1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints.

End point type

Secondary

End point timeframe

4 months

Notes
[17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: percentage of participants
number (confidence interval 95%)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	90.0 (47.3 to 98.5)	97.3 (89.6 to 99.3)

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 6 Months

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End point title

Monotherapy Only: Percentage of Participants With Overall Survival at 6 Months ^[18]

End point description

OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 6 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. Full Analysis Set consisted of all participants who received ≥1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints

End point type

Secondary

End point timeframe

6 months

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: percentage of participants
number (confidence interval 95%)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	90.0 (47.3 to 98.5)	97.3 (89.6 to 99.3)

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 8 Months

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End point title

Monotherapy Only: Percentage of Participants With Overall Survival at 8 Months ^[19]

End point description

OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 8 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. Full Analysis Set consisted of all participants who received ≥1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints.

End point type

Secondary

End point timeframe

8 months

Notes
[19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: percentage of participants
number (confidence interval 95%)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	90.0 (47.3 to 98.5)	94.0 (84.8 to 97.7)

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 10 Months

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End point title

Monotherapy Only: Percentage of Participants With Overall Survival at 10 Months ^[20]

End point description

OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 10 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. Full Analysis Set consisted of all participants who received ≥1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints.

End point type

Secondary

End point timeframe

10 months

Notes
[20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: percentage of participants
number (confidence interval 95%)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	83.3 (27.3 to 97.5)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	90.0 (47.3 to 98.5)	90.0 (78.8 to 95.4)

No statistical analyses for this end point

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 12 Months

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End point title

Monotherapy Only: Percentage of Participants With Overall Survival at 12 Months ^[21]

End point description

OS is defined as the time from the date of enrollment to the date of death from any cause. Kaplan-Meier estimates at 12 months and their confidence intervals are calculated with the log-log transformation methodology of Kalbfleisch and Prentice. Full Analysis Set consisted of all participants who received ≥1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints.

End point type

Secondary

End point timeframe

12 months

Notes
[21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: percentage of participants
number (confidence interval 95%)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	83.3 (27.3 to 97.5)	100.0 (100.0 to 100.0)	100.0 (100.0 to 100.0)	90.0 (47.3 to 98.5)	84.2 (69.8 to 92.1)

No statistical analyses for this end point

Secondary: Objective Response Rate (ORR) for ZN-c5 as a Monotherapy

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End point title

Objective Response Rate (ORR) for ZN-c5 as a Monotherapy ^[22]

End point description

ORR is defined as the number of participants with measurable disease who have at least 1 confirmed response of CR or PR prior to any evidence of progression (as defined by RECIST v1.1). Full Analysis Set consisted of all participants who received ≥1 dose of study drug and was used in the analyses of participant characteristics and efficacy endpoints.

End point type

Secondary

End point timeframe

24 weeks

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: Only reporting groups in which participants received monotherapy were evaluated for this end point.

End point values	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD
Number of subjects analysed	16	3	3	6	15	3	10	75
Units: participants	0	0	0	0	1	0	1	3

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

12 months

Adverse event reporting additional description

For the safety analysis, Phase 1 Monotherapy group was combined with Phase 2 Monotherapy group.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

25.1

Reporting group title

Phase 1 (Monotherapy): ZN-c5 50 mg QD

Reporting group description

Participants who received ZN-c5 50 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 75 mg QD

Reporting group description

Participants who received ZN-c5 75 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 100 mg QD

Reporting group description

Participants who received ZN-c5 100 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 75 mg BID

Reporting group description

Participants who received ZN-c5 75 mg BID in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 150 mg QD

Reporting group description

Participants who received ZN-c5 150 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 150 mg BID

Reporting group description

Participants who received ZN-c5 150 mg BID in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Monotherapy): ZN-c5 300 mg QD

Reporting group description

Participants who received ZN-c5 300 mg QD in Phase 1 were included in this arm.

Reporting group title

Phase 2 (Monotherapy): ZN-c5 50 mg QD

Reporting group description

Participants who received ZN-c5 50 mg QD in Phase 2 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 25mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 25 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 25mg BID + Palbociclib

Reporting group description

Participants who received ZN-c5 25 mg BID along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 50mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 50 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 50mg BID + Palbociclib

Reporting group description

Participants who received ZN-c5 50 mg BID along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 100mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 100 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Reporting group title

Phase 1 (Combination Therapy): ZNc5 150mg QD + Palbociclib

Reporting group description

Participants who received ZN-c5 150 mg QD along with Palbociclib (IBRANCE®) in Phase 1 were included in this arm.

Phase 1 (Monotherapy): ZN-c5 50 mg QD

Phase 1 (Monotherapy): ZN-c5 75 mg QD

Phase 1 (Monotherapy): ZN-c5 100 mg QD

Phase 1 (Monotherapy): ZN-c5 75 mg BID

Phase 1 (Monotherapy): ZN-c5 150 mg QD

Phase 1 (Monotherapy): ZN-c5 150 mg BID

Phase 1 (Monotherapy): ZN-c5 300 mg QD

Phase 2 (Monotherapy): ZN-c5 50 mg QD

Phase 1 (Combination Therapy): ZNc5 25mg QD + Palbociclib

Phase 1 (Combination Therapy): ZNc5 25mg BID + Palbociclib

Phase 1 (Combination Therapy): ZNc5 50mg QD + Palbociclib

Phase 1 (Combination Therapy): ZNc5 50mg BID + Palbociclib

Phase 1 (Combination Therapy): ZNc5 100mg QD + Palbociclib

Phase 1 (Combination Therapy): ZNc5 150mg QD + Palbociclib

Total subjects affected by serious adverse events

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

1 / 6 (16.67%)

2 / 15 (13.33%)

0 / 3 (0.00%)

2 / 10 (20.00%)

9 / 75 (12.00%)

4 / 10 (40.00%)

1 / 5 (20.00%)

2 / 18 (11.11%)

0 / 2 (0.00%)

2 / 12 (16.67%)

1 / 3 (33.33%)

number of deaths (all causes)

number of deaths resulting from adverse events

Injury, poisoning and procedural complications

Femur fracture

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Foot fracture

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Spinal fracture

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Vascular disorders

Embolism

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 18 (5.56%)

0 / 2 (0.00%)

0 / 12 (0.00%)

1 / 3 (33.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

Cardiac disorders

Cardiac disorder

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Nervous system disorders

Aphasia

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Headache

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ischaemic stroke

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 18 (5.56%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Transient ischaemic attack

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

1 / 6 (16.67%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

General disorders and administration site conditions

Pyrexia

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Immune system disorders

Drug hypersensitivity

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Gastrointestinal disorders

Abdominal pain

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Ascites

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Respiratory, thoracic and mediastinal disorders

Dyspnoea

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

2 / 10 (20.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pleural effusion

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

2 / 75 (2.67%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 2

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumothorax

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

1 / 12 (8.33%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pulmonary embolism

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 75 (1.33%)

0 / 10 (0.00%)

0 / 5 (0.00%)

1 / 18 (5.56%)

0 / 2 (0.00%)

0 / 12 (0.00%)

1 / 3 (33.33%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 1

0 / 0

0 / 1

deaths causally related to treatment / all

0 / 0

1 / 1

0 / 0

Renal and urinary disorders

Acute kidney injury

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Calculus urinary

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Musculoskeletal and connective tissue disorders

Arthalgia

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

1 / 3 (33.33%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Back pain

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

1 / 5 (20.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Infections and infestations

COVID-19

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 3 (0.00%)

0 / 10 (0.00%)

2 / 75 (2.67%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

0 / 2

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Cellulitis

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

1 / 15 (6.67%)

0 / 3 (0.00%)

0 / 10 (0.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Device related infection

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

1 / 10 (10.00%)

0 / 75 (0.00%)

0 / 10 (0.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

Pneumonia

subjects affected / exposed

0 / 16 (0.00%)

0 / 3 (0.00%)

0 / 6 (0.00%)

0 / 15 (0.00%)

0 / 3 (0.00%)

0 / 10 (0.00%)

1 / 75 (1.33%)

1 / 10 (10.00%)

0 / 5 (0.00%)

0 / 18 (0.00%)

0 / 2 (0.00%)

0 / 12 (0.00%)

0 / 3 (0.00%)

occurrences causally related to treatment / all

0 / 0

0 / 1

0 / 0

deaths causally related to treatment / all

0 / 0

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

Non-serious adverse events	Phase 1 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg QD	Phase 1 (Monotherapy): ZN-c5 100 mg QD	Phase 1 (Monotherapy): ZN-c5 75 mg BID	Phase 1 (Monotherapy): ZN-c5 150 mg QD	Phase 1 (Monotherapy): ZN-c5 150 mg BID	Phase 1 (Monotherapy): ZN-c5 300 mg QD	Phase 2 (Monotherapy): ZN-c5 50 mg QD	Phase 1 (Combination Therapy): ZNc5 25mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 25mg BID + Palbociclib	Phase 1 (Combination Therapy): ZNc5 50mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 50mg BID + Palbociclib	Phase 1 (Combination Therapy): ZNc5 100mg QD + Palbociclib	Phase 1 (Combination Therapy): ZNc5 150mg QD + Palbociclib
Total subjects affected by non serious adverse events
subjects affected / exposed	15 / 16 (93.75%)	3 / 3 (100.00%)	3 / 3 (100.00%)	6 / 6 (100.00%)	14 / 15 (93.33%)	3 / 3 (100.00%)	10 / 10 (100.00%)	55 / 75 (73.33%)	10 / 10 (100.00%)	5 / 5 (100.00%)	18 / 18 (100.00%)	2 / 2 (100.00%)	12 / 12 (100.00%)	3 / 3 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Cancer pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	1	1	0	0	0	0	0	0
Endometrial cancer
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Malignant pleural effusion
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Metastases to skin
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Vascular disorders
Hot flush
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	3 / 15 (20.00%)	0 / 3 (0.00%)	3 / 10 (30.00%)	2 / 75 (2.67%)	1 / 10 (10.00%)	1 / 5 (20.00%)	4 / 18 (22.22%)	1 / 2 (50.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	2	3	0	3	2	1	1	4	1	0	1
Hypertension
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	4 / 15 (26.67%)	0 / 3 (0.00%)	1 / 10 (10.00%)	3 / 75 (4.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	4	0	1	3	1	0	1	0	0	0
Hypotension
subjects affected / exposed	1 / 16 (6.25%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	1 / 75 (1.33%)	2 / 10 (20.00%)	0 / 5 (0.00%)	3 / 18 (16.67%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	0	1	1	1	2	0	3	0	0	0
Haematoma
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Lymphoedema
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	1	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	4 / 16 (25.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 6 (33.33%)	3 / 15 (20.00%)	1 / 3 (33.33%)	3 / 10 (30.00%)	6 / 75 (8.00%)	5 / 10 (50.00%)	2 / 5 (40.00%)	10 / 18 (55.56%)	0 / 2 (0.00%)	3 / 12 (25.00%)	2 / 3 (66.67%)
occurrences all number	4	1	0	2	3	1	3	6	5	2	10	0	3	2
Asthenia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	7 / 75 (9.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	7	0	0	0	0	0	0
Oedema peripheral
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 75 (2.67%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	2 / 12 (16.67%)	1 / 3 (33.33%)
occurrences all number	1	0	0	1	0	0	0	2	0	0	1	0	2	1
Pyrexia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	2	0	1	0	0	0	1	0	2	0
Chest pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 75 (4.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	3	0	0	0	0	0	0
Chills
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	1	0	1	0
Localised oedema
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Malaise
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Medical device site erythema
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Non-cardiac chest pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	1	0	0	0	0	0	1	0	0	0	0
Pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	1	1	0	0	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Reproductive system and breast disorders
Breast pain
subjects affected / exposed	1 / 16 (6.25%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 75 (2.67%)	0 / 10 (0.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	1	0	1	0	2	0	0	2	0	0	0
Vaginal discharge
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 75 (2.67%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	1	1	0	2	1	0	0	0	0	0
Breast necrosis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Pelvic pain
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0	0	0	0	0
Premature menopause
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Uterine haemorrhage
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Vaginal haemorrhage
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Vulva cyst
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Vulvovaginal dryness
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Vulvovaginal pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Vulvovaginal pruritus
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	2 / 16 (12.50%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	4 / 18 (22.22%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	0	0	0	2	0	1	0	0	1	4	1	0	0
Dyspnoea
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	7 / 75 (9.33%)	2 / 10 (20.00%)	1 / 5 (20.00%)	3 / 18 (16.67%)	0 / 2 (0.00%)	2 / 12 (16.67%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	2	0	1	7	2	1	3	0	2	1
Oropharyngeal pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	1 / 2 (50.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	1	0	1	0	0	0	2	1	1	0
Rhinitis allergic
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	1	1	0	0	1	0	0	0	1	0
Acute respiratory failure
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Dysphonia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Epistaxis
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	1	0	1	0	0	0
Haemoptysis
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Hiccups
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Mediastinal mass
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Nasal congestion
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Pleural effusion
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 75 (4.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	3	1	0	1	0	0	0
Pleuritic pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pneumonitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Pneumothorax
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	1	0
Productive cough
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	1	0	0	0
Pulmonary embolism
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Sinus disorder
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Upper-airway cough syndrome
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Wheezing
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	1 / 15 (6.67%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	6 / 18 (33.33%)	1 / 2 (50.00%)	1 / 12 (8.33%)	1 / 3 (33.33%)
occurrences all number	0	0	0	2	1	0	1	0	1	0	6	1	1	1
Anxiety
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	1	0	1	0	0	0	2	0	1	0
Affect lability
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	1	0
Delirium
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Depression
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Irritability
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0	1	0	0	0
Libido increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Mania
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Investigations
ALT increased
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 15 (13.33%)	1 / 3 (33.33%)	2 / 10 (20.00%)	6 / 75 (8.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	1 / 2 (50.00%)	2 / 12 (16.67%)	0 / 3 (0.00%)
occurrences all number	1	0	0	1	2	1	2	6	2	1	0	1	2	0
AST increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	1 / 3 (33.33%)	1 / 10 (10.00%)	7 / 75 (9.33%)	1 / 10 (10.00%)	2 / 5 (40.00%)	4 / 18 (22.22%)	0 / 2 (0.00%)	2 / 12 (16.67%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	2	1	1	7	1	2	4	0	2	1
Blood cholesterol increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	1 / 3 (33.33%)	1 / 10 (10.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	2 / 5 (40.00%)	4 / 18 (22.22%)	0 / 2 (0.00%)	2 / 12 (16.67%)	1 / 3 (33.33%)
occurrences all number	0	0	0	1	1	1	1	1	0	2	4	0	2	1
Blood creatinine increased
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	1 / 10 (10.00%)	6 / 75 (8.00%)	5 / 10 (50.00%)	1 / 5 (20.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	1	0	1	6	5	1	2	0	2	0
GGT increased
subjects affected / exposed	3 / 16 (18.75%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 15 (20.00%)	2 / 3 (66.67%)	2 / 10 (20.00%)	11 / 75 (14.67%)	1 / 10 (10.00%)	1 / 5 (20.00%)	1 / 18 (5.56%)	1 / 2 (50.00%)	2 / 12 (16.67%)	0 / 3 (0.00%)
occurrences all number	3	0	0	1	3	2	2	11	1	1	1	1	2	0
Lymphocyte count decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	1 / 3 (33.33%)	2 / 10 (20.00%)	3 / 75 (4.00%)	5 / 10 (50.00%)	1 / 5 (20.00%)	6 / 18 (33.33%)	1 / 2 (50.00%)	3 / 12 (25.00%)	2 / 3 (66.67%)
occurrences all number	0	0	0	1	1	1	2	3	5	1	6	1	3	2
Neutrophil count decreased
subjects affected / exposed	0 / 16 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	8 / 10 (80.00%)	3 / 5 (60.00%)	14 / 18 (77.78%)	1 / 2 (50.00%)	7 / 12 (58.33%)	3 / 3 (100.00%)
occurrences all number	0	1	0	1	1	0	0	0	8	3	14	1	7	3
Platelet count decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 15 (13.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	5 / 18 (27.78%)	0 / 2 (0.00%)	4 / 12 (33.33%)	1 / 3 (33.33%)
occurrences all number	0	0	0	1	2	0	0	0	2	1	5	0	4	1
White blood cell count decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 15 (20.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	2 / 75 (2.67%)	7 / 10 (70.00%)	3 / 5 (60.00%)	14 / 18 (77.78%)	1 / 2 (50.00%)	11 / 12 (91.67%)	2 / 3 (66.67%)
occurrences all number	0	0	0	1	3	1	1	2	7	3	14	1	11	2
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 16 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	1 / 3 (33.33%)	0 / 10 (0.00%)	7 / 75 (9.33%)	0 / 10 (0.00%)	1 / 5 (20.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	2	1	0	7	0	1	2	0	0	0
Electrocardiogram QT prolonged
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	6 / 75 (8.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	6	0	1	0	0	0	0
Weight decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	1 / 3 (33.33%)	0 / 10 (0.00%)	4 / 75 (5.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	1	0	4	1	0	1	0	1	0
Activated partial thromboplastin time prolonged
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0	1	0	0	0
Blood bicarbonate increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Blood bilirubin increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Blood phosphorus increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Blood urea increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	0	0	0	0
C-reactive protein increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
CD4 lymphocytes decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Carbohydrate antigen 27.29 increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 75 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	2	0	0	0	0	0
Carcinoembryonic antigen increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	1	0	0	0	0	0
International normalised ratio increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 75 (2.67%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	0	1	0	0	0
Low density lipoprotein increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Monocyte count decreased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Platelet count increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Tumour marker increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Weight increased
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	2	0	0	1
Breast injury
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Eye contusion
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Fall
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	2	0	0	0	0	1	0	0	0	0	1
Procedural pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	1	0
Rib fracture
subjects affected / exposed	0 / 16 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Skin abrasion
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Skin laceration
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Thermal burn
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Tooth injury
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Upper limb fracture
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Wound
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Cardiac disorders
Sinus tachycardia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	3 / 75 (4.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	2	0	1	3	0	0	0	0	0	0
Arrhythmia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Palpitations
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0	0	0	0	0
Pericarditis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Sinus bradycardia
subjects affected / exposed	2 / 16 (12.50%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	1	0	0	0	0	0	0
Nervous system disorders
Dizziness
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	2 / 10 (20.00%)	0 / 5 (0.00%)	3 / 18 (16.67%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	2	0	0	1	2	0	3	0	0	0
Headache
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	4 / 15 (26.67%)	1 / 3 (33.33%)	3 / 10 (30.00%)	3 / 75 (4.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	3 / 12 (25.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1	1	4	1	3	3	1	0	2	0	3	1
Anosmia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Carotid artery stenosis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Dysgeusia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Hyperaesthesia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Memory impairment
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	1	0	0	0
Muscle spasticity
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Myoclonus
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Neuropathy peripheral
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Paraesthesia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	1	1	0	0	1	0	0	0	0	0	1
Peripheral sensory neuropathy
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Sciatica
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Syncope
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Transient ischaemic attack
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 15 (20.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	5 / 75 (6.67%)	5 / 10 (50.00%)	2 / 5 (40.00%)	12 / 18 (66.67%)	1 / 2 (50.00%)	5 / 12 (41.67%)	2 / 3 (66.67%)
occurrences all number	0	0	0	1	3	1	2	5	5	2	12	1	5	2
Neutropenia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	6 / 75 (8.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	6	0	0	0	0	0	0
Lymphadenopathy
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Pancytopenia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Ear and labyrinth disorders
Ear discomfort
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Ear pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	1	0	0	0
Middle ear inflammation
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Tinnitus
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Vertigo
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Eye disorders
Diplopia
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Dry eye
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Eyelid function disorder
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Ocular hyperaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Photopsia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Uveitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Vision blurred
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Visual field defect
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Gastrointestinal disorders
Constipation
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	2 / 15 (13.33%)	1 / 3 (33.33%)	0 / 10 (0.00%)	2 / 75 (2.67%)	1 / 10 (10.00%)	1 / 5 (20.00%)	4 / 18 (22.22%)	0 / 2 (0.00%)	1 / 12 (8.33%)	1 / 3 (33.33%)
occurrences all number	0	0	1	0	2	1	0	2	1	1	4	0	1	1
Diarrhoea
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 15 (20.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	7 / 75 (9.33%)	1 / 10 (10.00%)	2 / 5 (40.00%)	3 / 18 (16.67%)	0 / 2 (0.00%)	2 / 12 (16.67%)	1 / 3 (33.33%)
occurrences all number	1	0	0	1	3	1	1	7	1	2	3	0	2	1
Dyspepsia
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	1 / 3 (33.33%)	1 / 10 (10.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	4 / 18 (22.22%)	0 / 2 (0.00%)	4 / 12 (33.33%)	1 / 3 (33.33%)
occurrences all number	1	0	0	0	2	1	1	0	1	0	4	0	4	1
Nausea
subjects affected / exposed	2 / 16 (12.50%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 6 (33.33%)	6 / 15 (40.00%)	2 / 3 (66.67%)	4 / 10 (40.00%)	6 / 75 (8.00%)	3 / 10 (30.00%)	3 / 5 (60.00%)	6 / 18 (33.33%)	0 / 2 (0.00%)	4 / 12 (33.33%)	2 / 3 (66.67%)
occurrences all number	2	1	0	2	6	2	4	6	3	3	6	0	4	2
Stomatitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	3 / 18 (16.67%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	1	0	0	0	1	1	3	0	0	1
Vomiting
subjects affected / exposed	1 / 16 (6.25%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	3 / 15 (20.00%)	2 / 3 (66.67%)	2 / 10 (20.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	1	1	0	0	3	2	2	0	1	1	2	0	1	0
Abdominal pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	2 / 3 (66.67%)	1 / 10 (10.00%)	4 / 75 (5.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	1 / 3 (33.33%)
occurrences all number	0	0	0	1	0	2	1	4	0	0	0	0	1	1
Abdominal distension
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	1
Abdominal pain upper
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	0	0	0	0
Dry mouth
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Enterocolitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Flatulence
subjects affected / exposed	0 / 16 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0	0	0	0	0
Frequent bowel movements
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	1	0	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	0
Lip swelling
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Mouth ulceration
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Oesophageal pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Oral pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	1	0	0	0
Toothache
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 75 (2.67%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	2	0	1	0	0	0	0
Hepatobiliary disorders
Hepatic pain
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Rash maculo-papular
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	3 / 10 (30.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	1 / 12 (8.33%)	2 / 3 (66.67%)
occurrences all number	0	0	0	1	0	0	0	1	3	0	2	0	1	2
Alopecia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	2	0	1	0
Pruritus
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	2 / 10 (20.00%)	2 / 5 (40.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	1	0	0	1	2	2	0	0	0	0
Blister
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Dermatitis acneiform
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Dermatitis contact
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	1	0	0	0
Hyperhidrosis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Hypertrichosis
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Night sweats
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	0	0
Onychoclasis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Psoriasis
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	0	0	0	0	0
Rash
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	1	0	0	0	0	0	1	0	0	0
Rosacea
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Skin hyperpigmentation
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Skin lesion
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	1
Skin mass
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0	0	0	0	0
Renal and urinary disorders
Proteinuria
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	1	0	0	1
Dysuria
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	0	0	0	0	0	0	0
Haematuria
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Micturition urgency
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	1	0	0	0	0	0	0
Nephrolithiasis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	1 / 2 (50.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	1	0	0
Urinary incontinence
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Urinary retention
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Urinary tract pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	1	0	0	0	0	0	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Goitre
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	2 / 16 (12.50%)	0 / 3 (0.00%)	1 / 3 (33.33%)	2 / 6 (33.33%)	3 / 15 (20.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	4 / 75 (5.33%)	0 / 10 (0.00%)	2 / 5 (40.00%)	9 / 18 (50.00%)	0 / 2 (0.00%)	4 / 12 (33.33%)	1 / 3 (33.33%)
occurrences all number	2	0	1	2	3	1	2	4	0	2	9	0	4	1
Back pain
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	2 / 15 (13.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	5 / 75 (6.67%)	0 / 10 (0.00%)	2 / 5 (40.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	1	1	2	0	1	5	0	2	2	0	0	0
Myalgia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	4 / 18 (22.22%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	1	1	1	0	0	0	0	0	4	0	0	1
Pain in extremity
subjects affected / exposed	1 / 16 (6.25%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 15 (13.33%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	3 / 18 (16.67%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	1	0	1	2	0	1	0	1	0	3	0	0	0
Bone pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 15 (13.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	4 / 75 (5.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	2	0	0	4	1	0	0	0	1	0
Flank pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	1	0	2	0	0	0
Muscle spasms
subjects affected / exposed	0 / 16 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0	1	0	2	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 16 (0.00%)	1 / 3 (33.33%)	0 / 3 (0.00%)	2 / 6 (33.33%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	1	0	2	0	0	0	1	0	0	0	0	0	0
Arthritis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Chest wall mass
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Muscle fatigue
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Muscular weakness
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	1	0	0	0	1	1	0	0	0
Musculoskeletal pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	1	0	0	0	0	0	0	0	0	0
Musculoskeletal stiffness
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Neck pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	1	0	0	0	0	1	0	1	0
Osteonecrosis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Osteonecrosis of jaw
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pain in jaw
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	1	1	0	0	0
Plantar fasciitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	1 / 3 (33.33%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	0	1
Sacral pain
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	1	0	0	0	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 75 (4.00%)	3 / 10 (30.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	3	3	0	2	0	0	0
COVID-19
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	8 / 75 (10.67%)	1 / 10 (10.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	2 / 12 (16.67%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	1	0	0	8	1	0	1	0	2	0
Upper respiratory tract infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	2	0	0	0	1	0	2	0	1	0
Catheter site infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Cellulitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	1	0	0	0	0	0
Conjunctivitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Cystitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Device related infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	1	0
Diverticulitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	1 / 3 (33.33%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	1	0	1	0	0	0	0	0	0
Gastrointestinal infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 75 (2.67%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	2	0	0	0	0	0	0
Otitis media
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Pneumonia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	1	0	0	0	1	0
Rash pustular
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Sepsis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0	0	0	0	0
Sinusitis
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	1 / 2 (50.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	0	0	0	1	1	0
Skin infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	2	0	0	0
Tooth infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1	0	0	0
Vaginal infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0	0	0	1	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	3 / 15 (20.00%)	1 / 3 (33.33%)	2 / 10 (20.00%)	0 / 75 (0.00%)	3 / 10 (30.00%)	1 / 5 (20.00%)	3 / 18 (16.67%)	1 / 2 (50.00%)	5 / 12 (41.67%)	0 / 3 (0.00%)
occurrences all number	1	0	0	1	3	1	2	0	3	1	3	1	5	0
Hypertriglyceridaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	2 / 15 (13.33%)	1 / 3 (33.33%)	2 / 10 (20.00%)	0 / 75 (0.00%)	2 / 10 (20.00%)	1 / 5 (20.00%)	5 / 18 (27.78%)	0 / 2 (0.00%)	3 / 12 (25.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	2	1	2	0	2	1	5	0	3	0
Hypoalbuminaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	2 / 10 (20.00%)	1 / 75 (1.33%)	2 / 10 (20.00%)	0 / 5 (0.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	2	1	2	0	2	0	1	0
Hypocalcaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 15 (13.33%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 75 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	4 / 18 (22.22%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	2	1	0	0	2	0	4	0	0	0
Hypokalaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	5 / 10 (50.00%)	0 / 5 (0.00%)	4 / 18 (22.22%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	1	0	5	0	4	0	0	0
Hyponatraemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	2 / 6 (33.33%)	2 / 15 (13.33%)	0 / 3 (0.00%)	2 / 10 (20.00%)	1 / 75 (1.33%)	3 / 10 (30.00%)	1 / 5 (20.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	2	2	0	2	1	3	1	2	0	1	0
Hypophosphataemia
subjects affected / exposed	0 / 16 (0.00%)	2 / 3 (66.67%)	0 / 3 (0.00%)	0 / 6 (0.00%)	3 / 15 (20.00%)	1 / 3 (33.33%)	0 / 10 (0.00%)	0 / 75 (0.00%)	2 / 10 (20.00%)	0 / 5 (0.00%)	4 / 18 (22.22%)	1 / 2 (50.00%)	2 / 12 (16.67%)	0 / 3 (0.00%)
occurrences all number	0	2	0	0	3	1	0	0	2	0	4	1	2	0
Decreased appetite
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	1 / 3 (33.33%)	1 / 10 (10.00%)	4 / 75 (5.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	1	1	4	0	0	1	0	1	0
Hypercalcaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	1 / 3 (33.33%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	3 / 75 (4.00%)	1 / 10 (10.00%)	1 / 5 (20.00%)	2 / 18 (11.11%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	1	0	0	0	0	3	1	1	2	0	0	0
Hypoglycaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	2 / 15 (13.33%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	2	0	0	0	0	0	1	0	0	0
Hypomagnesaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	3 / 15 (20.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	1 / 75 (1.33%)	0 / 10 (0.00%)	0 / 5 (0.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	3	0	0	1	0	0	1	0	1	0
Dehydration
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	1 / 10 (10.00%)	0 / 75 (0.00%)	1 / 10 (10.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	1	0	1	0	0	0	1	0
Glucose tolerance impaired
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	0	0	1	0
Gout
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	0 / 5 (0.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0	0	0	0
Hyperkalaemia
subjects affected / exposed	0 / 16 (0.00%)	0 / 3 (0.00%)	0 / 3 (0.00%)	1 / 6 (16.67%)	1 / 15 (6.67%)	0 / 3 (0.00%)	0 / 10 (0.00%)	2 / 75 (2.67%)	0 / 10 (0.00%)	1 / 5 (20.00%)	1 / 18 (5.56%)	0 / 2 (0.00%)	0 / 12 (0.00%)	0 / 3 (0.00%)
occurrences all number	0	0	0	1	1	0	0	2	0	1	1	0	0	0
Hyperphosphataemia
subjects affected / exposed	1 / 16 (6.25%)	0 / 3 (0.00%)	0 / 3 (0.00%)	0 / 6 (0.00%)	0 / 15 (0.00%)	0 / 3 (0.00%)	0 / 10 (0.00%)	0 / 75 (0.00%)	0 / 10 (0.00%)	1 / 5 (20.00%)	0 / 18 (0.00%)	0 / 2 (0.00%)	1 / 12 (8.33%)	0 / 3 (0.00%)
occurrences all number	1	0	0	0	0	0	0	0	0	1	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

09 Apr 2018

EudraCT number added and investigator prompt removed from title page.

12 Jul 2018

The language throughout the protocol clarified, updated and streamlined to improve flow and readability.

25 Jun 2019

The study design updated.

14 Feb 2020

The study design updated.

14 Sep 2020

The study design updated.

20 Apr 2021

The clarification for Phase 2 assessment, food intake and abbreviated Pharmacokinetic sampling updated.

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.

In the Phase 2 Monotherapy efficacy analysis, efficacy was to be determined by the CBR, combining results with similar treatment groups. Phase 1 Monotherapy group was combined with Phase 2 Monotherapy group. Phase 2 Combination part was not initiated

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Clinical Benefit Rate for ZN-c5 as a Monotherapy

Primary: Clinical Benefit Rate for ZN-c5 as a Monotherapy

Primary: Best Overall Response (BOR) for ZN-c5 as a Monotherapy

Primary: Best Overall Response (BOR) for ZN-c5 as a Monotherapy

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 2 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival (PFS) at 2 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 4 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 4 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 6 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 6 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 8 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 8 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 10 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 12 Months

Secondary: Monotherapy Only: Percentage of Participants With Progression-Free Survival at 12 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 2 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival (OS) at 2 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 4 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 4 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 6 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 6 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 8 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 8 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 10 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 10 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 12 Months

Secondary: Monotherapy Only: Percentage of Participants With Overall Survival at 12 Months

Secondary: Objective Response Rate (ORR) for ZN-c5 as a Monotherapy

Secondary: Objective Response Rate (ORR) for ZN-c5 as a Monotherapy

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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