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Clinical Trial Results:
A Phase 3 Randomized Double-Blind Trial of Maintenance with Niraparib Versus Placebo in Patients with Platinum Sensitive Ovarian Cancer

Summary
EudraCT number	2013-000685-11
Trial protocol	SE DE AT GB DK IT HU ES BE PL
Global end of trial date	26 Dec 2021

Results information
Results version number	v3(current)
This version publication date	16 Jun 2023
First version publication date	01 Jan 2023
Other versions	v1 , v2
Version creation reason

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

213356

ISRCTN number

US NCT number

WHO universal trial number (UTN)

Sponsor organisation name

GSK

Sponsor organisation address

980 Great West Road, Brentford, Middlesex, United Kingdom, TW8 9GS

Public contact

GSK Response Center, GSK, 1 8664357343, GSKClinicalSupportHD@gsk.com

Scientific contact

GSK Response Center, GSK, 1 8664357343, GSKClinicalSupportHD@gsk.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

27 Mar 2023

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

26 Dec 2021

Was the trial ended prematurely?

Main objective of the trial

The primary objective of this study is to evaluate efficacy of niraparib as maintenance therapy in participants who have platinum sensitive ovarian cancer as assessed by the prolongation of progression-free survival (PFS)

Protection of trial subjects

Protocol Amendment 7 introduced less visits burden to participants, as so called “Extended Cycle Visit”: – Required in-clinic visit every cycle (28 days) optional; participants may visit the clinic every three cycles (84 days). – Option for in-home nursing visit or site local clinic/hospital except for visit every three cycles which must be performed at the site – Study assessments which can be performed by study coordinator through telephone contact include Adverse event, ConMed and Eastern Cooperative Oncology Group. – Study assessments which can be performed at the in home nursing visits, local clinic or hospital include vitals, blood draw (complete blood count, chemistry, CA-125) and dispensation of study drug Protective measures were also taken temporarily during Coronavirus disease-19 pandemic 2020/2021 by allowing most assessments done remotely, or locally; and providing study drug supply by courier to participants.

Background therapy

Evidence for comparator

Actual start date of recruitment

21 Jun 2013

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

United States: 198

Country: Number of subjects enrolled

Austria: 6

Country: Number of subjects enrolled

Belgium: 18

Country: Number of subjects enrolled

Canada: 66

Country: Number of subjects enrolled

Germany: 52

Country: Number of subjects enrolled

Denmark: 48

Country: Number of subjects enrolled

Spain: 48

Country: Number of subjects enrolled

France: 47

Country: Number of subjects enrolled

United Kingdom: 32

Country: Number of subjects enrolled

Hungary: 3

Country: Number of subjects enrolled

Israel: 18

Country: Number of subjects enrolled

Italy: 19

Country: Number of subjects enrolled

Norway: 12

Country: Number of subjects enrolled

Poland: 15

Country: Number of subjects enrolled

Sweden: 14

Worldwide total number of subjects

596

EEA total number of subjects

282

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)

384

From 65 to 84 years

212

85 years and over

Subject disposition

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Recruitment details

This was a randomized, double-blind study conducted to analyze maintenance with niraparib versus placebo in participants with ovarian cancer.

Screening details

A total of 596 participants were enrolled in the study. The results presented are based on the data cut-off date of 31 March 2021 (which aligns with the time of the study unblinding) and the post-unblinding safety data until the end of study (01-April-2021 to 26-December-2021).

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

gBRCA Niraparib

Arm description

Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Niraparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received 3x100 milligrams of niraparib as oral dose.

gBRCA Placebo

Arm description

Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received placebo matching 3x capsules as oral dose.

Non-gBRCA Niraparib

Arm description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Arm type

Experimental

Investigational medicinal product name

Niraparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received 3x100 milligrams of niraparib as oral dose.

Non-gBRCA Placebo

Arm description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received placebo matching 3x capsules as oral dose.

FE sub-study: Fasted/fed

Arm description

Participants received a single dose of 3x100 mg capsules of niraparib administered orally following a minimum 10-hour overnight fast in Period 1 followed by 300 mg capsules of niraparib administered orally as single dose in fed condition (high-fat meal) in Period 2. There was a washout period of 7 days between treatment periods.

Arm type

Experimental

Investigational medicinal product name

Niraparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received 3x100 milligrams of niraparib as oral dose.

FE sub-study: Fed/fasted

Arm description

Participants received single dose of 3x100 mg capsules of niraparib administered orally following a high-fat meal in Period 1 followed by 3x100 mg capsules of niraparib administered orally as single dose in fasted condition in Period 2. There was a washout period of 7 days between treatment periods.

Arm type

Experimental

Investigational medicinal product name

Niraparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received 3x100 milligrams of niraparib as oral dose.

QTc sub-study: Niraparib

Arm description

Participants received Niraparib 300 mg once daily orally.

Arm type

Experimental

Investigational medicinal product name

Niraparib

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Participants received 3x100 milligrams of niraparib as oral dose.

Number of subjects in period 1 ^[1]	gBRCA Niraparib	gBRCA Placebo	Non-gBRCA Niraparib	Non-gBRCA Placebo	FE sub-study: Fasted/fed	FE sub-study: Fed/fasted	QTc sub-study: Niraparib
Started	138	65	234	116	8	9	26
Completed	0	0	0	0	7	8	0
Not completed	138	65	234	116	1	1	26
Consent withdrawn by subject	20	11	30	14	-	-	4
Disease progression	-	-	-	2	-	-	-
Subject Moved to Rollover Study	6	-	9	-	-	-	-
Adverse event, non-fatal	-	-	-	-	-	1	-
Death	72	29	146	68	-	-	5
Transferred to other arm/group	-	-	-	-	1	-	-
Subject unblinded by sponsor	27	20	33	26	-	-	-
Other reasons	6	3	11	5	-	-	17
Lost to follow-up	7	2	5	1	-	-	-

Notes
[1] - The number of subjects transferring in and out of the arms in the period are not the same. It is expected the net number of transfers in and out of the arms in a period, will be zero.
Justification: Subject is transferred to another treatment group

Baseline characteristics

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Reporting group title

gBRCA Niraparib

Reporting group description

Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression.

Reporting group title

gBRCA Placebo

Reporting group description

Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression.

Reporting group title

Non-gBRCA Niraparib

Reporting group description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Reporting group title

Non-gBRCA Placebo

Reporting group description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Reporting group title

FE sub-study: Fasted/fed

Reporting group description

Reporting group title

FE sub-study: Fed/fasted

Reporting group description

Reporting group title

QTc sub-study: Niraparib

Reporting group description

Participants received Niraparib 300 mg once daily orally.

Reporting group values	gBRCA Niraparib	gBRCA Placebo	Non-gBRCA Niraparib	Non-gBRCA Placebo	FE sub-study: Fasted/fed	FE sub-study: Fed/fasted	QTc sub-study: Niraparib	Total
Number of subjects	138	65	234	116	8	9	26	596
Age Categorical
Units: Participants
<=18 years	0	0	0	0	0	0	0	0
Between 18 and 64 years	110	49	130	69	5	5	16	384
>=65 years	28	16	104	47	3	4	10	212
Sex: Female, Male
Units: Participants
Female	138	65	234	116	8	9	26	596
Male	0	0	0	0	0	0	0	0
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaska Native	1	0	0	0	0	0	1	2
Asian	2	3	10	4	0	0	1	20
Native Hawaiian or Other Pacific Islander	0	0	0	0	1	0	0	1
Black or African American	1	1	4	1	1	0	3	11
White	123	55	201	101	6	9	21	516
Unknown or Not Reported	11	6	19	10	0	0	0	46

End points

Top of page

Reporting group title

gBRCA Niraparib

Reporting group description

Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression.

Reporting group title

gBRCA Placebo

Reporting group description

Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression.

Reporting group title

Non-gBRCA Niraparib

Reporting group description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Reporting group title

Non-gBRCA Placebo

Reporting group description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Reporting group title

FE sub-study: Fasted/fed

Reporting group description

Reporting group title

FE sub-study: Fed/fasted

Reporting group description

Reporting group title

QTc sub-study: Niraparib

Reporting group description

Participants received Niraparib 300 mg once daily orally.

Subject analysis set title

non-gBRCAmut HRD+ Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Niraparib (300 mg) once daily in 28-day cycles until disease progression in participants with homologous recombination deficiency-positive (HRD+) tumors Niraparib vs. Placebo 2:1 ratio

Subject analysis set title

non-gBRCAmut HRD+ Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo once daily in 28-day cycles until disease progression patients with homologous recombination deficiency-positive (HRD+) tumors Niraparib vs. Placebo 2:1 ratio

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Niraparib (300 mg) once daily in 28-day cycles until disease progression in patients without germline BRCA mutation Niraparib vs. Placebo 2:1 ratio

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Placebo once daily in 28-day cycles until disease progression in patients without germline BRCA mutation Niraparib vs. Placebo 2:1 ratio

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Niraparib

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

non-gBRCA Placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

FE Niraparib Fasted

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received Niraparib 300 mg in fasted condition

Subject analysis set title

FE Niraparib Fed

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received Niraparib 300 mg in fed condition

Subject analysis set title

FE Niraparib Fasted

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received Niraparib 300 mg in fasted condition

Subject analysis set title

FE Niraparib Fed

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants received Niraparib 300 mg in fed condition

Subject analysis set title

gBRCA Niraparib (PSU)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants with germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression

Subject analysis set title

gBRCA Placebo (PSU)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants with germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Subject analysis set title

Non-gBRCA Niraparib (PSU)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression

Subject analysis set title

Non-gBRCA Placebo (PSU)

Subject analysis set type

Sub-group analysis

Subject analysis set description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Primary: Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer gene (BRCA) Mutation (gBRCA)

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End point title

Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer gene (BRCA) Mutation (gBRCA) ^[1]

End point description

PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. Intent-to-treat population was defined as all randomized participants with participants analyzed according to the study drug assigned via randomization. 99999 indicates Upper limit of confidence interval (CI) was not estimable as upper limits of CI for survivor function were above 0.5 (SAS PROC LIFETEST).

End point type

Primary

End point timeframe

From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years 7 months and 4 days

Notes
[1] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	138 ^[2]	65 ^[3]
Units: months
median (confidence interval 95%)	21 (12.9 to 99999)	5.5 (3.8 to 7.2)

Notes
[2] - Intent-to-treat population
[3] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001 ^[4]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.27

Confidence interval

level

95%

sides

2-sided

lower limit

0.173

upper limit

0.41

Notes
[4] - Two-sided P-value. PFS was independently evaluated in gBRCAmut cohort and non-gBRCAmut cohort.

Primary: Progression-Free Survival (PFS) in Cohort with No Germline BCRA with homologous recombination deficiency-positive (HRD+) tumors (non-gBRCAmut HRD+)

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End point title

Progression-Free Survival (PFS) in Cohort with No Germline BCRA with homologous recombination deficiency-positive (HRD+) tumors (non-gBRCAmut HRD+)

End point description

PFS was defined as the time between randomization and disease progression or death from any cause. Computed tomography or magnetic resonance imaging to assess disease progression was performed at baseline, every 8 weeks through cycle 14, and then every 12 weeks until treatment discontinuation. The objective assessment of disease progression was determined by means of central radiologic and clinical review, according to Response Evaluation Criteria in Solid Tumors (RECIST),version 1.1, which was performed in a blinded fashion. PD was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study.

End point type

Primary

End point timeframe

From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days

End point values	non-gBRCAmut HRD+ Niraparib	non-gBRCAmut HRD+ Placebo
Number of subjects analysed	106 ^[5]	56 ^[6]
Units: months
median (confidence interval 95%)	12.9 (8.1 to 15.9)	3.8 (3.5 to 5.7)

Notes
[5] - Intent-to-treat population
[6] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

non-gBRCAmut HRD+ Niraparib v non-gBRCAmut HRD+ Placebo

Number of subjects included in analysis

162

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001 ^[7]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.38

Confidence interval

level

95%

sides

2-sided

lower limit

0.243

upper limit

0.586

Notes
[7] - Two-sided P-value. PFS was independently evaluated in gBRCAmut cohort and non-gBRCAmut cohort. Hierarchical testing: HRD+ subset tested first. If HRD+ subset demonstrated statistical significance, overall non-gBRCA cohort was then tested

Primary: Progression-Free Survival (PFS) in Cohort with No Germline BRCA Mutation (non-gBRCA)

Top of page

End point title

Progression-Free Survival (PFS) in Cohort with No Germline BRCA Mutation (non-gBRCA)

End point description

End point type

Primary

End point timeframe

From date of randomization to the earliest date of disease progression or death from any cause, up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	234 ^[8]	116 ^[9]
Units: Months
median (confidence interval 95%)	9.3 (7.2 to 11.2)	3.9 (3.7 to 5.5)

Notes
[8] - Intent-to-treat population
[9] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

P-value

< 0.0001 ^[10]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.45

Confidence interval

level

95%

sides

2-sided

lower limit

0.338

upper limit

0.607

Notes
[10] - Two-sided P-value. PFS was independently evaluated in gBRCAmut cohort and non-gBRCAmut cohort. Hierarchical testing: HRD+ subset tested first. If HRD+ subset demonstrated statistical significance, overall non-gBRCA cohort was then tested.

Secondary: Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

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End point title

Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) ^[11]

End point description

The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death.

End point type

Secondary

End point timeframe

From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days

Notes
[11] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	138 ^[12]	65 ^[13]
Units: Months
median (confidence interval 95%)	19.1 (14.6 to 21.9)	8.6 (6.9 to 12.2)

Notes
[12] - Intent-to-treat population
[13] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0005 ^[14]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.57

Confidence interval

level

95%

sides

2-sided

lower limit

0.412

upper limit

0.783

Notes
[14] - Two-sided P-value.

Secondary: Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation

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End point title

Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation

End point description

The TFST was defined as the time from the date of randomization to the start date of the first subsequent anti-cancer therapy or death

End point type

Secondary

End point timeframe

From date of randomization to the earliest date of first subsequent therapy or death, up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	234 ^[15]	116 ^[16]
Units: Months
median (confidence interval 95%)	12.4 (10.9 to 14.5)	7.4 (5.9 to 8.7)

Notes
[15] - Intent-to-treat population
[16] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[17]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.58

Confidence interval

level

95%

sides

2-sided

lower limit

0.454

upper limit

0.74

Notes
[17] - Two-sided P-value.

Secondary: Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)

Top of page

End point title

Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA) ^[18]

End point description

Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment

End point type

Secondary

End point timeframe

From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days

Notes
[18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	138 ^[19]	65 ^[20]
Units: Months
median (confidence interval 95%)	20.0 (16.2 to 23.3)	9.4 (7.9 to 10.4)

Notes
[19] - Intent-to-treat population
[20] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[21]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.39

Confidence interval

level

95%

sides

2-sided

lower limit

0.268

upper limit

0.561

Notes
[21] - Two-sided P-value.

Secondary: Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)

Top of page

End point title

Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA) ^[22]

End point description

Progression-Free Survival 2 was defined as the date of randomization in the current study to the earlier date of assessment of progression on the next anti-cancer therapy following study treatment or death due to any cause. Progression was determined by the investigator via clinical and radiographic assessment using the same criteria as used in the current study.

End point type

Secondary

End point timeframe

From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days

Notes
[22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	138 ^[23]	65 ^[24]
Units: Months
median (confidence interval 95%)	29.9 (24.8 to 33.4)	22.7 (19.5 to 25.9)

Notes
[23] - Intent-to-treat population
[24] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0302 ^[25]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.7

Confidence interval

level

95%

sides

2-sided

lower limit

0.5

upper limit

0.968

Notes
[25] - Two-sided P-value.

Secondary: Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation

Top of page

End point title

Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation

End point description

Chemotherapy-Free Interval was defined as the time from the last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment

End point type

Secondary

End point timeframe

From date of last platinum therapy prior to randomization to the initiation of the next anti-cancer therapy after maintenance treatment, up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	234 ^[26]	116 ^[27]
Units: Months
median (confidence interval 95%)	13.4 (11.3 to 14.8)	8.7 (6.9 to 10.0)

Notes
[26] - Intent-to-treat population
[27] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

< 0.0001 ^[28]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.56

Confidence interval

level

95%

sides

2-sided

lower limit

0.428

upper limit

0.727

Notes
[28] - Two-sided P-value.

Secondary: Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation

Top of page

End point title

Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation

End point description

End point type

Secondary

End point timeframe

From treatment randomization to the earlier of the date of disease progression on the next anti-cancer therapy following study treatment or death due to any cause, up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	234 ^[29]	116 ^[30]
Units: Months
median (confidence interval 95%)	19.5 (17.1 to 22.3)	16.1 (13.6 to 22.8)

Notes
[29] - Intent-to-treat population
[30] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0748 ^[31]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.8

Confidence interval

level

95%

sides

2-sided

lower limit

0.627

upper limit

1.022

Notes
[31] - Two-sided P-value.

Secondary: Overall Survival in Cohort With Germline BRCA Mutation (gBRCA)

Top of page

End point title

Overall Survival in Cohort With Germline BRCA Mutation (gBRCA) ^[32]

End point description

Overall survival was defined as the date of randomization to the date of death by any cause.

End point type

Secondary

End point timeframe

From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days

Notes
[32] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	138 ^[33]	65 ^[34]
Units: Months
median (confidence interval 95%)	40.9 (34.9 to 52.9)	38.1 (27.6 to 47.3)

Notes
[33] - Intent-to-treat population
[34] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.358 ^[35]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.85

Confidence interval

level

95%

sides

2-sided

lower limit

0.606

upper limit

1.198

Notes
[35] - Two-sided P-value.

Secondary: Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

Top of page

End point title

Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA) ^[36]

End point description

TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.

End point type

Secondary

End point timeframe

From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days

Notes
[36] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	138 ^[37]	65 ^[38]
Units: Months
median (confidence interval 95%)	29.7 (23.3 to 33.4)	19.6 (14.4 to 25.5)

Notes
[37] - Intent-to-treat population
[38] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0061 ^[39]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.63

Confidence interval

level

95%

sides

2-sided

lower limit

0.451

upper limit

0.878

Notes
[39] - Two-sided P-value.

Secondary: Overall Survival in Cohort With No Germline BRCA Mutation

Top of page

End point title

Overall Survival in Cohort With No Germline BRCA Mutation

End point description

Overall survival was defined as the date of randomization to the date of death by any cause.

End point type

Secondary

End point timeframe

From treatment randomization to date of death by any cause, up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	234 ^[40]	116 ^[41]
Units: Months
median (confidence interval 95%)	31.0 (27.8 to 35.6)	34.8 (27.9 to 41.4)

Notes
[40] - Intent-to-treat population
[41] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.6868 ^[42]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

1.06

Confidence interval

level

95%

sides

2-sided

lower limit

0.813

upper limit

1.369

Notes
[42] - Two-sided P-value.

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6

Top of page

End point title

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6 ^[43]

End point description

Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participantsrespond to their symptom experience over the past 7 days using a 5-point Likert scale score from “not at all” (0) to “very much” (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)

Notes
[43] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	95 ^[44]	36 ^[45]
Units: Scores on a scale
arithmetic mean (standard deviation)	0.5 ± 3.77	-0.5 ± 4.27

Notes
[44] - Intent-to-treat population
[45] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4

Top of page

End point title

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4 ^[46]

End point description

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)

Notes
[46] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	109 ^[47]	43 ^[48]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.1 ± 4.07	-0.3 ± 3.88

Notes
[47] - Intent-to-treat population
[48] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2

Top of page

End point title

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2 ^[49]

End point description

Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from “not at all” (0) to “very much” (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)

Notes
[49] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	114 ^[50]	55 ^[51]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.8 ± 4.58	-0.3 ± 3.19

Notes
[50] - Intent-to-treat population
[51] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation

Top of page

End point title

Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation

End point description

TSST was defined as the date of randomization to the earlier of the start date of second follow-up anti-cancer treatment or death.

End point type

Secondary

End point timeframe

From the date of randomization to the start date of the second subsequent anti-cancer therapy, up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	234 ^[52]	116 ^[53]
Units: Months
median (confidence interval 95%)	20.3 (18.0 to 23.4)	16.7 (14.9 to 21.3)

Notes
[52] - Intent-to-treat population
[53] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.1674 ^[54]

Method

Logrank

Parameter type

Hazard ratio (HR)

Point estimate

0.84

Confidence interval

level

95%

sides

2-sided

lower limit

0.654

upper limit

1.077

Notes
[54] - Two-sided P-value.

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4

Top of page

End point title

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4

End point description

Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from “not at all” (0) to “very much” (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	150 ^[55]	77 ^[56]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.7 ± 4.16	-0.9 ± 4.23

Notes
[55] - Intent-to-treat population
[56] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at post-progression

Top of page

End point title

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at post-progression ^[57]

End point description

Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from “not at all” (0) to “very much” (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Cycle 1 Day 1, Each cycle was of 28 days) and up to 7 years, 7 months and 4 days

Notes
[57] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
Justification: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	80 ^[58]	37 ^[59]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.751 ± 4.4342	-1.324 ± 4.5034

Notes
[58] - Intent-to-treat population
[59] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2

Top of page

End point title

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2

End point description

Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from “not at all” (0) to “very much” (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	181 ^[60]	97 ^[61]
Units: Scores on a scale
arithmetic mean (standard deviation)	-1.0 ± 3.79	-0.3 ± 2.84

Notes
[60] - Intent-to-treat population
[61] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6

Top of page

End point title

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6

End point description

Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from “not at all” (0) to “very much” (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	124 ^[62]	50 ^[63]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.2 ± 3.76	-0.9 ± 3.43

Notes
[62] - Intent-to-treat population
[63] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4

Top of page

End point title

Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4 ^[64]

End point description

EQ-5D-5L is a well-validated, general preference-based, health-related Quality of Life (QoL) instrument. The EQ-5D-5L encompasses 5 domains, asking participants to rate their perceived health state today on the following dimensions: Mobility, Self-Care, Usual Activities, Pain/Discomfort, and Anxiety/Depression. Each domain has 5 possible levels: "no problems" (Level 1), "slight problems" (Level 2), "moderate problems" (Level 3), "severe problems" (Level 4), and "extreme problems" (Level 5). Responses for 5 dimensions together formed a 5-figure description of health state (e.g.11111 indicates no problems in all 5 dimensions). Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value.Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)

Notes
[64] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	113 ^[65]	44 ^[66]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.010 ± 0.1225	-0.035 ± 0.1156

Notes
[65] - Intent-to-treat population
[66] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6

Top of page

End point title

Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6 ^[67]

End point description

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)

Notes
[67] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	99 ^[68]	36 ^[69]
Units: Scores on a scale
arithmetic mean (standard deviation)	0.002 ± 0.1116	-0.004 ± 0.1463

Notes
[68] - Intent-to-treat population
[69] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2

Top of page

End point title

Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2 ^[70]

End point description

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)

Notes
[70] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	118 ^[71]	59 ^[72]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.008 ± 0.1092	-0.008 ± 0.1354

Notes
[71] - Intent-to-treat population
[72] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at post-progression

Top of page

End point title

Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at post-progression

End point description

Functional Assessment of Cancer Therapy-Ovarian Symptom Index is a validated, 8-item measure of symptom response to treatment for ovarian cancer. Participants respond to their symptom experience over the past 7 days using a 5-point Likert scale score from “not at all” (0) to “very much” (4). The total score was calculated by multiplying the sum of all items scored by 8 and dividing the result by the number of responses. The total symptom index was calculated as the total of the 8 scores, ranging from 0 ("severely symptomatic") to 32 ("asymptomatic"). A positive change from Baseline indicates improvement. Baseline was latest non-missing pre-dose assessment on or before randomization date. Change from Baseline was calculated by subtracting the Baseline value from the post-dose visit value. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	146 ^[73]	82 ^[74]
Units: Scores on a scale
arithmetic mean (standard deviation)	-2.595 ± 5.5700	-1.801 ± 4.0290

Notes
[73] - Intent-to-treat population
[74] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at post-progression

Top of page

End point title

Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at post-progression

End point description

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	149 ^[75]	84 ^[76]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.047 ± 0.1355	-0.050 ± 0.1351

Notes
[75] - Intent-to-treat population
[76] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6

Top of page

End point title

Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6

End point description

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 6 (Each cycle was of 28 days)

End point values	non-gBRCA Placebo	non-gBRCA Niraparib
Number of subjects analysed	50 ^[77]	127 ^[78]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.011 ± 0.0949	0.005 ± 0.1097

Notes
[77] - Intent-to-treat population
[78] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4

Top of page

End point title

Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4

End point description

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 4 (Each cycle was of 28 days)

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	155 ^[79]	80 ^[80]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.004 ± 0.1077	-0.014 ± 0.0870

Notes
[79] - Intent-to-treat population
[80] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at post-progression

Top of page

End point title

Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at post-progression ^[81]

End point description

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and up to 7 years, 7 months and 4 days

Notes
[81] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	81 ^[82]	38 ^[83]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.041 ± 0.1192	-0.013 ± 0.1580

Notes
[82] - Intent-to-treat population
[83] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2

Top of page

End point title

Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2

End point description

End point type

Secondary

End point timeframe

Baseline (Pre-dose on Day 1) and at Cycle 2 (Each cycle was of 28 days)

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	185 ^[84]	96 ^[85]
Units: Scores on a scale
arithmetic mean (standard deviation)	-0.007 ± 0.1013	-0.011 ± 0.1015

Notes
[84] - Intent-to-treat population
[85] - Intent-to-treat population

No statistical analyses for this end point

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Baseline

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Baseline ^[86]

End point description

A Neuropathy Questionnaire measures the participant's symptom experience over the past 7 days using a 5-point Likert scale of “not at all” (0) to “very much” (4). There are 2 items that ask if the participant’s feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. The Neuropathy Questionnaire was used to determine the chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant’s QoL. Two thresholds were used. For the first, a participant was determined to have CIPN if a score greater than 0 (“not at all”) was recorded for either item. For the second, CIPN was assigned if a participant recorded a score greater than 1 (“a little bit”). Baseline was latest non-missing pre-dose assessment on or before randomization date.

End point type

Secondary

End point timeframe

At Baseline

Notes
[86] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	138 ^[87]	65 ^[88]
Units: Participants
Feet, 0-Not at all	47	26
Feet, 1-A little bit	32	12
Feet, 2-Somewhat	24	9
Feet, 3-Quite a bit	21	10
Feet, 4-Very much	9	6
Hands, 0-Not at all	80	37
Hands, 1-A little bit	28	13
Hands, 2-Somewhat	8	6
Hands, 3-Quite a bit	14	5
Hands, 4-Very much	3	2

Notes
[87] - Intent-to-treat population
[88] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8794

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

203

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7969

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 2

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 2 ^[89]

End point description

A Neuropathy Questionnaire measures participant's symptom experience over past 7 days using 5-point Likert scale of “not at all” (0) to “very much” (4). There are 2 items that ask if participant’s feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. Neuropathy Questionnaire was used to determine chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant’s QoL. Two thresholds were used. For first, participant was determined to have CIPN if a score greater than 0 (“not at all”) was recorded for either item. For second, CIPN was assigned if participant recorded a score greater than 1 (“a little bit”). Only those participants with data available at indicated time points were analyzed

End point type

Secondary

End point timeframe

At Cycle 2 (Each cycle was of 28 days)

Notes
[89] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	132 ^[90]	64 ^[91]
Units: Participants
Feet, 0-Not at all	48	25
Feet, 1-A little bit	22	5
Feet, 2-Somewhat	17	15
Feet, 3-Quite a bit	20	10
Feet, 4-Very much	8	3
Hands, 0-Not at all	73	31
Hands, 1-A little bit	19	16
Hands, 2-Somewhat	13	6
Hands, 3-Quite a bit	7	2
Hands, 4-Very much	3	2

Notes
[90] - Intent-to-treat population
[91] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2399

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

196

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4584

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 4

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 4 ^[92]

End point description

End point type

Secondary

End point timeframe

At Cycle 4 (Each cycle was of 28 days)

Notes
[92] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	120 ^[93]	54 ^[94]
Units: Participants
Feet, 0-Not at all	47	20
Feet, 1-A little bit	22	6
Feet, 2-Somewhat	20	7
Feet, 3-Quite a bit	15	8
Feet, 4-Very much	6	2
Hands, 0-Not at all	70	29
Hands, 1-A little bit	18	6
Hands, 2-Somewhat	16	3
Hands, 3-Quite a bit	4	4
Hands, 4-Very much	2	1

Notes
[93] - Intent-to-treat population
[94] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

174

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.4705

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

174

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8566

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 6

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 6 ^[95]

End point description

End point type

Secondary

End point timeframe

At Cycle 6 (Each cycle was of 28 days)

Notes
[95] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	105 ^[96]	41 ^[97]
Units: Participants
Feet, 0-Not at all	44	17
Feet, 1-A little bit	17	5
Feet, 2-Somewhat	13	7
Feet, 3-Quite a bit	15	5
Feet, 4-Very much	9	2
Hands, 0-Not at all	54	21
Hands, 1-A little bit	25	8
Hands, 2-Somewhat	10	4
Hands, 3-Quite a bit	6	2
Hands, 4-Very much	2	1

Notes
[96] - Intent-to-treat population
[97] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

146

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9923

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

146

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.8521

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at post-progression

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at post-progression ^[98]

End point description

End point type

Secondary

End point timeframe

Up to 7 years, 7 months and 4 days

Notes
[98] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo
Number of subjects analysed	104 ^[99]	49 ^[100]
Units: Participants
Feet, 0-Not at all	31	15
Feet, 1-A little bit	20	9
Feet, 2-Somewhat	7	3
Feet, 3-Quite a bit	15	7
Feet, 4-Very much	7	3
Hands, 0-Not at all	44	26
Hands, 1-A little bit	18	4
Hands, 2-Somewhat	8	3
Hands, 3-Quite a bit	7	4
Hands, 4-Very much	3	0

Notes
[99] - Intent-to-treat population
[100] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.3518

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

gBRCA Niraparib v gBRCA Placebo

Number of subjects included in analysis

153

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9997

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Baseline

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Baseline

End point description

End point type

Secondary

End point timeframe

At Baseline

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	234 ^[101]	116 ^[102]
Units: Participants
Feet, 0-Not at all	71	40
Feet, 1-A little bit	58	26
Feet, 2-Somewhat	37	16
Feet, 3-Quite a bit	43	21
Feet, 4-Very much	18	9
Hands, 0-Not at all	120	48
Hands, 1-A little bit	56	37
Hands, 2-Somewhat	28	12
Hands, 3-Quite a bit	15	11
Hands, 4-Very much	8	2

Notes
[101] - Intent-to-treat population
[102] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9367

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

350

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2502

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Cycle 2

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Cycle 2

End point description

End point type

Secondary

End point timeframe

At Cycle 2 (Each cycle was of 28 days)

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	212 ^[103]	113 ^[104]
Units: Participants
Feet, 0-Not at all	69	32
Feet, 1-A little bit	39	17
Feet, 2-Somewhat	30	22
Feet, 3-Quite a bit	34	18
Feet, 4-Very much	9	8
Hands, 0-Not at all	100	44
Hands, 1-A little bit	38	24
Hands, 2-Somewhat	20	19
Hands, 3-Quite a bit	17	5
Hands, 4-Very much	4	3

Notes
[103] - Intent-to-treat population
[104] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

325

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.164

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

325

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5037

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Cycle 4

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Cycle 4

End point description

A Neuropathy Questionnaire measures participant's symptom experience over past 7 days using 5-point Likert scale of “not at all” (0) to “very much” (4). There are 2 items that ask if participant’s feet (item 1) or hands (item 2) feel numb or have prickling/tingling feelings. Neuropathy Questionnaire was used to determine chemotherapy-induced peripheral neuropathy (CIPN) status of each participant as well as provide an anchor for interpreting the impact of CIPN on participant’s QoL. Two thresholds were used. For first, participant was determined to have CIPN if a score greater than 0 (“not at all”) was recorded for either item. For second, CIPN was assigned if participant recorded a score greater than 1 (“a little bit”). Change from Baseline was calculated as on-treatment visit value minus Baseline value. Baseline was latest non-missing pre-dose assessment on or before randomization date.Only those participants with data available at indicated time points were analyzed.

End point type

Secondary

End point timeframe

At Cycle 4 (Each cycle was of 28 days)

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	181 ^[105]	95 ^[106]
Units: Participants
Feet, 0-Not at all	54	31
Feet, 1-A little bit	37	16
Feet, 2-Somewhat	34	17
Feet, 3-Quite a bit	20	11
Feet, 4-Very much	9	5
Hands, 0-Not at all	89	43
Hands, 1-A little bit	29	21
Hands, 2-Somewhat	14	10
Hands, 3-Quite a bit	14	3
Hands, 4-Very much	6	1

Notes
[105] - Intent-to-treat population
[106] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.247

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

276

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.9599

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Cycle 6

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Cycle 6

End point description

End point type

Secondary

End point timeframe

At Cycle 6 (Each cycle was of 28 days)

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	144 ^[107]	56 ^[108]
Units: Participants
Feet, 0-Not at all	43	16
Feet, 1-A little bit	29	10
Feet, 2-Somewhat	30	11
Feet, 3-Quite a bit	18	9
Feet, 4-Very much	5	5
Hands, 0-Not at all	68	29
Hands, 1-A little bit	30	10
Hands, 2-Somewhat	13	6
Hands, 3-Quite a bit	9	5
Hands, 4-Very much	3	0

Notes
[107] - Intent-to-treat population
[108] - Intent-to-treat population

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Hands

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.7459

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Statistical analysis description

Analysis for gBRCA Niraparib vs gBRCA Placebo-Feet

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

200

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.5921

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at post-progression

Top of page

End point title

Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at post-progression

End point description

End point type

Secondary

End point timeframe

Up to 7 years, 7 months and 4 days

End point values	non-gBRCA Niraparib	non-gBRCA Placebo
Number of subjects analysed	185 ^[109]	105 ^[110]
Units: Participants
Feet, 0-Not at all	57	32
Feet, 1-A little bit	45	12
Feet, 2-Somewhat	23	16
Feet, 3-Quite a bit	19	16
Feet, 4-Very much	5	8
Hands, 0-Not at all	88	48
Hands, 1-A little bit	35	15
Hands, 2-Somewhat	13	9
Hands, 3-Quite a bit	7	10
Hands, 4-Very much	3	1

Notes
[109] - Intent-to-treat population
[110] - Intent-to-treat population

Statistical Analysis 1

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.2798

Method

Pearson's Chi-squared test

Confidence interval

Statistical Analysis 1

Comparison groups

non-gBRCA Niraparib v non-gBRCA Placebo

Number of subjects included in analysis

290

Analysis specification

Pre-specified

Analysis type

superiority

P-value

= 0.0259

Method

Pearson's Chi-squared test

Confidence interval

Secondary: Number of participants with non-serious adverse events (AEs) and serious AEs (SAEs)

Top of page

End point title

Number of participants with non-serious adverse events (AEs) and serious AEs (SAEs) ^[111]

End point description

An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. Data presented for this outcome measure is based on the data cut-off date of 31-March-2021, which aligns with the time of the study unblinding. Safety Population consisted of all participants who ingested any amount of study drug.

End point type

Secondary

End point timeframe

Up to 7 years, 7 months and 6 days

Notes
[111] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	gBRCA Niraparib	gBRCA Placebo	Non-gBRCA Niraparib	Non-gBRCA Placebo
Number of subjects analysed	136 ^[112]	65 ^[113]	231 ^[114]	114 ^[115]
Units: Participants
Non-serious AEs	136	62	231	110
SAEs	51	9	76	20

Notes
[112] - Safety Population
[113] - Safety Population
[114] - Safety Population
[115] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with non-serious AEs and SAEs (Post-study unblinding)

Top of page

End point title

Number of participants with non-serious AEs and SAEs (Post-study unblinding)

End point description

An AE is any untoward medical occurrence that occurs in a participants or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that at any dose which results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not serious adverse events were considered as non serious adverse events. The data is presented for post-study unblinding duration 01-Apr-2021 to 26-Dec-2021

End point type

Secondary

End point timeframe

Up to 8 months, 26 days

End point values	gBRCA Niraparib (PSU)	gBRCA Placebo (PSU)	Non-gBRCA Niraparib (PSU)	Non-gBRCA Placebo (PSU)
Number of subjects analysed	22 ^[116]	8 ^[117]	31 ^[118]	13 ^[119]
Units: Participants
Non-serious AEs	0	0	0	0
SAEs	0	0	0	0

Notes
[116] - Safety Population
[117] - Safety Population
[118] - Safety Population
[119] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with non-serious AEs and SAEs in QTc sub-study

Top of page

End point title

Number of participants with non-serious AEs and SAEs in QTc sub-study ^[120]

End point description

End point type

Secondary

End point timeframe

Up to 5 years 10 months and 22 days

Notes
[120] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	QTc sub-study: Niraparib
Number of subjects analysed	26 ^[121]
Units: Participants
Non-serious AEs	24
SAEs	12

Notes
[121] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with non-serious AEs and SAEs in FE sub-study

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End point title

Number of participants with non-serious AEs and SAEs in FE sub-study

End point description

End point type

Secondary

End point timeframe

Up to 2 years 3 months and 11 days

End point values	FE Niraparib Fasted	FE Niraparib Fed
Number of subjects analysed	16 ^[122]	16 ^[123]
Units: Participants
Non-serious AEs	4	6
SAEs	1	0

Notes
[122] - Safety Population
[123] - Safety Population

No statistical analyses for this end point

Secondary: Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC[0-last]) following administration of Niraparib (FE sub-study)

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End point title

Area under the plasma concentration-time curve from time 0 to the last quantifiable concentration (AUC[0-last]) following administration of Niraparib (FE sub-study)

End point description

Blood samples were collected at indicated time points to analyze the AUC(0-last) of niraparib. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose

End point values	FE Niraparib Fasted	FE Niraparib Fed
Number of subjects analysed	16 ^[124]	15
Units: Nanograms*hour per milliliter
arithmetic mean (standard deviation)	28638.1 ± 17911.86	27186.4 ± 14111.37

Notes
[124] - Pharmacokinetic population

Statistical Analysis 1

Comparison groups

FE Niraparib Fasted v FE Niraparib Fed

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Ratio of Least square mean

Point estimate

1.068

Confidence interval

level

90%

sides

2-sided

lower limit

0.978

upper limit

1.166

Secondary: Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC[0-infinity]) following administration of Niraparib (FE sub-study)

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End point title

Area under the plasma concentration-time curve from time 0 extrapolated to infinity (AUC[0-infinity]) following administration of Niraparib (FE sub-study)

End point description

Blood samples were collected at indicated time points to analyze AUC(0-infinity) of niraparib. Pharmacokinetic population consisted of all participants who received at least one dose of study drug, with sufficient data available to calculate parameters. Only those participants with data available at the specified time points were analyzed.

End point type

Secondary

End point timeframe

Pre-dose and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose

End point values	FE Niraparib Fasted	FE Niraparib Fed
Number of subjects analysed	15 ^[125]	14 ^[126]
Units: Nanograms*hour per milliliter
arithmetic mean (standard deviation)	29016.1 ± 18405.23	31194 ± 16894.88

Notes
[125] - Pharmacokinetic population
[126] - Pharmacokinetic population

Statistical Analysis 1

Comparison groups

FE Niraparib Fasted v FE Niraparib Fed

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Ratio of Least square mean

Point estimate

1.1

Confidence interval

level

90%

sides

2-sided

lower limit

0.997

upper limit

1.216

Secondary: Terminal elimination half-life (t1/2) following administration of Niraparib (FE sub-study)

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End point title

Terminal elimination half-life (t1/2) following administration of Niraparib (FE sub-study)

End point description

Blood samples were collected at indicated time points to analyze the t1/2 of niraparib. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose

End point values	FE Niraparib Fasted	FE Niraparib Fed
Number of subjects analysed	16 ^[127]	14 ^[128]
Units: Hour
arithmetic mean (standard deviation)	50.5 ± 17.87	47.9 ± 17.54

Notes
[127] - Pharmacokinetic population
[128] - Pharmacokinetic population

No statistical analyses for this end point

Secondary: Maximum observed plasma concentration (Cmax) following administration of Niraparib (FE sub-study)

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End point title

Maximum observed plasma concentration (Cmax) following administration of Niraparib (FE sub-study)

End point description

Blood samples were collected at indicated time points to analyze the maximum observed plasma concentration of niraparib. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose

End point values	FE Niraparib Fasted	FE Niraparib Fed
Number of subjects analysed	16 ^[129]	15
Units: Nanograms per milliliter
arithmetic mean (standard deviation)	803.7 ± 403.35	582.1 ± 228.57

Notes
[129] - Pharmacokinetic population

Statistical Analysis 1

Comparison groups

FE Niraparib Fasted v FE Niraparib Fed

Number of subjects included in analysis

Analysis specification

Pre-specified

Analysis type

Method

Parameter type

Ratio of Least square mean

Point estimate

0.785

Confidence interval

level

90%

sides

2-sided

lower limit

0.695

upper limit

0.886

Secondary: Time to reach maximum (tmax) following administration of Niraparib (FE sub-study)

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End point title

Time to reach maximum (tmax) following administration of Niraparib (FE sub-study)

End point description

Blood samples were collected at indicated time points to analyze the tmax of niraparib. Only those participants with data available at the indicated time points were analyzed.

End point type

Secondary

End point timeframe

Pre-dose (Day -1) and at 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, 72, 96, 120 hours post dose

End point values	FE Niraparib Fasted	FE Niraparib Fed
Number of subjects analysed	16 ^[130]	15
Units: Hour
median (full range (min-max))	3.1 (1.7 to 6.1)	6.1 (1.2 to 23)

Notes
[130] - Pharmacokinetic population

No statistical analyses for this end point

Secondary: Number of participants with maximum post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) greater than pre-specified thresholds

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End point title

Number of participants with maximum post-Baseline QT Interval Corrected by Fridericia's Formula (QTcF) greater than pre-specified thresholds ^[131]

End point description

12-lead electrocardiogram was obtained at indicated time points using an automated electrocardiogram machine that measured QTcF interval. The number of participants with maximum post-Baseline ECG value exceeding the following limits have been reported: QTcF interval >450 and <= 480 milliseconds (msec) and >500 msec.

End point type

Secondary

End point timeframe

At Baseline (Cycle 1 Day 1, each cycle was of 28 days)

Notes
[131] - 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: This endpoint is only reporting on a subset of the arms that are contained in the baseline period

End point values	QTc sub-study: Niraparib
Number of subjects analysed	26 ^[132]
Units: Participants
>450 msec	2
>480 msec	0
>500 msec	0

Notes
[132] - Safety Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

All-cause mortality, non-serious AEs (non-SAEs) and SAEs were collected up to 8 years, 6 months and 6 days

Adverse event reporting additional description

Safety Population was used to assess SAEs and non-SAEs, which comprised of all participants who ingested any amount of study drug. The data is presented in separate arms for adverse events before unblinding (data cut-off date of 31-March-2021) and post-study unblinding until the end of study (01-April-2021 to 26-December-2021).

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

23.0

Reporting group title

gBRCA Niraparib

Reporting group description

Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression.

Reporting group title

gBRCA Placebo

Reporting group description

Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression

Reporting group title

Non-gBRCA Niraparib

Reporting group description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression.

Reporting group title

Non-gBRCA Placebo

Reporting group description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression

Reporting group title

FE Niraparib Fasted

Reporting group description

Participants received Niraparib 300 mg in fasted condition

Reporting group title

Non-gBRCA Placebo (PSU)

Reporting group description

Participants without germline BRCA mutation received matching placebo once daily orally in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 1-Apr-2021 to 26-Dec-2021.

Reporting group title

QTc sub-study: Niraparib

Reporting group description

Participants received Niraparib 300 mg once daily orally.

Reporting group title

gBRCA Niraparib (PSU)

Reporting group description

Participants with germline breast cancer gene (gBRCA) mutation received oral dose of niraparib 300 milligrams (mg) once daily in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 1-Apr-2021 to 26-Dec-2021

Reporting group title

gBRCA Placebo (PSU)

Reporting group description

Participants with germline BRCA mutation received oral dose of placebo matching niraparib once daily in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 1-Apr-2021 to 26-Dec-2021.

Reporting group title

Non-gBRCA Niraparib (PSU)

Reporting group description

Participants without germline BRCA mutation received oral dose of niraparib 300 mg once daily orally in 28-day cycles until disease progression. This arm presents data for post-study unblinding duration 1-Apr-2021 to 26-Dec-2021.

Reporting group title

FE Niraparib Fed

Reporting group description

Participants received Niraparib 300 mg in fed condition

Serious adverse events	gBRCA Niraparib	gBRCA Placebo	Non-gBRCA Niraparib	Non-gBRCA Placebo	FE Niraparib Fasted	Non-gBRCA Placebo (PSU)	QTc sub-study: Niraparib	gBRCA Niraparib (PSU)	gBRCA Placebo (PSU)	Non-gBRCA Niraparib (PSU)	FE Niraparib Fed
Total subjects affected by serious adverse events
subjects affected / exposed	51 / 136 (37.50%)	9 / 65 (13.85%)	76 / 231 (32.90%)	20 / 114 (17.54%)	1 / 16 (6.25%)	0 / 13 (0.00%)	12 / 26 (46.15%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
number of deaths (all causes)	72	29	146	68	0	0	5	0	0	0	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to central nervous system
subjects affected / exposed	1 / 136 (0.74%)	1 / 65 (1.54%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Myelodysplastic syndrome
subjects affected / exposed	5 / 136 (3.68%)	1 / 65 (1.54%)	2 / 231 (0.87%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	5 / 5	0 / 1	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute myeloid leukaemia
subjects affected / exposed	6 / 136 (4.41%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	6 / 6	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	2 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute erythroid leukaemia
subjects affected / exposed	0 / 136 (0.00%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metastases to peritoneum
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Undifferentiated sarcoma
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Squamous cell carcinoma
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intraductal proliferative breast lesion
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ovarian cancer recurrent
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Breast cancer
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vascular disorders
Hypertensive crisis
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Peripheral artery thrombosis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Non-cardiac chest pain
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Mucosal inflammation
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	2 / 136 (1.47%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General physical health deterioration
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Disease progression
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	2 / 231 (0.87%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactoid reaction
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Breast disorder
subjects affected / exposed	0 / 136 (0.00%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Pleural effusion
subjects affected / exposed	1 / 136 (0.74%)	1 / 65 (1.54%)	2 / 231 (0.87%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Acute pulmonary oedema
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dyspnoea
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory disorder
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pleuritic pain
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Asthma
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonitis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Psychiatric disorders
Suicide attempt
subjects affected / exposed	0 / 136 (0.00%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Behaviour disorder
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anxiety
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hallucination
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Depression
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Product issues
Thrombosis in device
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Investigations
Neutrophil count decreased
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Troponin increased
subjects affected / exposed	0 / 136 (0.00%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Platelet count decreased
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	2 / 231 (0.87%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transaminases increased
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Injury, poisoning and procedural complications
Hip fracture
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Incisional hernia
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Post procedural discomfort
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transfusion reaction
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Procedural complication
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Product use complaint
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cardiac disorders
Cardiac failure
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tachycardia
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Angina pectoris
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sinus tachycardia
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pericardial effusion
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Coronary artery stenosis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nervous system disorders
Depressed level of consciousness
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Syncope
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Transient ischaemic attack
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Blood and lymphatic system disorders
Thrombocytopenia
subjects affected / exposed	18 / 136 (13.24%)	0 / 65 (0.00%)	23 / 231 (9.96%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	3 / 26 (11.54%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	38 / 38	0 / 0	36 / 36	0 / 0	0 / 0	0 / 0	9 / 9	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancytopenia
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	2 / 231 (0.87%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	3 / 3	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Neutropenia
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Anaemia
subjects affected / exposed	4 / 136 (2.94%)	0 / 65 (0.00%)	13 / 231 (5.63%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	6 / 6	0 / 0	15 / 15	0 / 0	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Febrile neutropenia
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Small intestinal obstruction
subjects affected / exposed	3 / 136 (2.21%)	0 / 65 (0.00%)	6 / 231 (2.60%)	4 / 114 (3.51%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0	0 / 7	0 / 5	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ascites
subjects affected / exposed	2 / 136 (1.47%)	0 / 65 (0.00%)	0 / 231 (0.00%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Constipation
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	3 / 231 (1.30%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 3	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain upper
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	1 / 231 (0.43%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nausea
subjects affected / exposed	1 / 136 (0.74%)	2 / 65 (3.08%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 2	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus paralytic
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pancreatitis
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Intestinal obstruction
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Subileus
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	2 / 231 (0.87%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal hernia
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal pain lower
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Impaired gastric emptying
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Malignant gastrointestinal obstruction
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Obstruction gastric
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Vomiting
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	2 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Oesophagitis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Ileus
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abdominal distension
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholestasis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatic failure
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Nephrolithiasis
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hydronephrosis
subjects affected / exposed	0 / 136 (0.00%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract obstruction
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal failure
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthropathy
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Bronchitis
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Erysipelas
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 136 (0.74%)	1 / 65 (1.54%)	2 / 231 (0.87%)	1 / 114 (0.88%)	1 / 16 (6.25%)	0 / 13 (0.00%)	1 / 26 (3.85%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 2	0 / 1	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infection
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	3 / 231 (1.30%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	1 / 4	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pyelonephritis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Empyema
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Device related infection
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Wound infection
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Tracheobronchitis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	1 / 231 (0.43%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hypomagnesaemia
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Type 2 diabetes mellitus
subjects affected / exposed	1 / 136 (0.74%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Decreased appetite
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

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

Non-serious adverse events	gBRCA Niraparib	gBRCA Placebo	Non-gBRCA Niraparib	Non-gBRCA Placebo	FE Niraparib Fasted	Non-gBRCA Placebo (PSU)	QTc sub-study: Niraparib	gBRCA Niraparib (PSU)	gBRCA Placebo (PSU)	Non-gBRCA Niraparib (PSU)	FE Niraparib Fed
Total subjects affected by non serious adverse events
subjects affected / exposed	136 / 136 (100.00%)	62 / 65 (95.38%)	231 / 231 (100.00%)	110 / 114 (96.49%)	4 / 16 (25.00%)	0 / 13 (0.00%)	24 / 26 (92.31%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	6 / 16 (37.50%)
Vascular disorders
Deep vein thrombosis
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0
Hypertension
subjects affected / exposed	38 / 136 (27.94%)	5 / 65 (7.69%)	46 / 231 (19.91%)	4 / 114 (3.51%)	0 / 16 (0.00%)	0 / 13 (0.00%)	4 / 26 (15.38%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	123	6	207	5	0	0	4	0	0	0	0
Hot flush
subjects affected / exposed	10 / 136 (7.35%)	3 / 65 (4.62%)	24 / 231 (10.39%)	6 / 114 (5.26%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	11	3	43	8	0	0	0	0	0	0	0
General disorders and administration site conditions
Pain
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0
Fatigue
subjects affected / exposed	66 / 136 (48.53%)	19 / 65 (29.23%)	110 / 231 (47.62%)	38 / 114 (33.33%)	0 / 16 (0.00%)	0 / 13 (0.00%)	13 / 26 (50.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	1 / 16 (6.25%)
occurrences all number	134	37	189	53	0	0	20	0	0	0	1
Catheter site pain
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	1 / 16 (6.25%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Asthenia
subjects affected / exposed	27 / 136 (19.85%)	3 / 65 (4.62%)	36 / 231 (15.58%)	13 / 114 (11.40%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	75	3	81	17	0	0	0	0	0	0	0
Oedema peripheral
subjects affected / exposed	12 / 136 (8.82%)	2 / 65 (3.08%)	15 / 231 (6.49%)	6 / 114 (5.26%)	0 / 16 (0.00%)	0 / 13 (0.00%)	5 / 26 (19.23%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	15	3	23	10	0	0	5	0	0	0	0
Pyrexia
subjects affected / exposed	11 / 136 (8.09%)	4 / 65 (6.15%)	16 / 231 (6.93%)	7 / 114 (6.14%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	1 / 16 (6.25%)
occurrences all number	17	5	23	8	0	0	0	0	0	0	1
Influenza like illness
subjects affected / exposed	8 / 136 (5.88%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	11	1	0	0	0	0	0	0	0	0	0
Mucosal inflammation
subjects affected / exposed	7 / 136 (5.15%)	1 / 65 (1.54%)	19 / 231 (8.23%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	9	1	23	2	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	26 / 136 (19.12%)	2 / 65 (3.08%)	42 / 231 (18.18%)	8 / 114 (7.02%)	1 / 16 (6.25%)	0 / 13 (0.00%)	4 / 26 (15.38%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	36	4	60	9	1	0	6	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Dysphonia
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	1 / 16 (6.25%)
occurrences all number	0	0	0	0	0	0	0	0	0	0	1
Dyspnoea
subjects affected / exposed	23 / 136 (16.91%)	3 / 65 (4.62%)	49 / 231 (21.21%)	12 / 114 (10.53%)	0 / 16 (0.00%)	0 / 13 (0.00%)	4 / 26 (15.38%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	34	4	62	14	0	0	4	0	0	0	0
Epistaxis
subjects affected / exposed	7 / 136 (5.15%)	0 / 65 (0.00%)	12 / 231 (5.19%)	4 / 114 (3.51%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	9	0	15	4	0	0	0	0	0	0	0
Oropharyngeal pain
subjects affected / exposed	11 / 136 (8.09%)	2 / 65 (3.08%)	16 / 231 (6.93%)	3 / 114 (2.63%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	19	2	21	4	0	0	0	0	0	0	0
Psychiatric disorders
Insomnia
subjects affected / exposed	26 / 136 (19.12%)	6 / 65 (9.23%)	67 / 231 (29.00%)	10 / 114 (8.77%)	0 / 16 (0.00%)	0 / 13 (0.00%)	3 / 26 (11.54%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	36	7	88	11	0	0	3	0	0	0	0
Anxiety
subjects affected / exposed	12 / 136 (8.82%)	7 / 65 (10.77%)	21 / 231 (9.09%)	5 / 114 (4.39%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	27	11	27	5	0	0	0	0	0	0	0
Depression
subjects affected / exposed	9 / 136 (6.62%)	2 / 65 (3.08%)	14 / 231 (6.06%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	14	3	21	1	0	0	0	0	0	0	0
Investigations
White blood cell count decreased
subjects affected / exposed	20 / 136 (14.71%)	5 / 65 (7.69%)	22 / 231 (9.52%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	42	14	64	0	0	0	5	0	0	0	0
Platelet count decreased
subjects affected / exposed	34 / 136 (25.00%)	1 / 65 (1.54%)	45 / 231 (19.48%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	3 / 26 (11.54%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	85	1	132	2	0	0	8	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	23 / 136 (16.91%)	3 / 65 (4.62%)	31 / 231 (13.42%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	4 / 26 (15.38%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	64	5	79	2	0	0	6	0	0	0	0
Blood creatinine increased
subjects affected / exposed	11 / 136 (8.09%)	3 / 65 (4.62%)	15 / 231 (6.49%)	3 / 114 (2.63%)	1 / 16 (6.25%)	0 / 13 (0.00%)	4 / 26 (15.38%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	29	4	32	3	1	0	6	0	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	13 / 231 (5.63%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	19	1	0	0	0	0	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	7 / 136 (5.15%)	0 / 65 (0.00%)	15 / 231 (6.49%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	15	0	27	2	0	0	0	0	0	0	0
Alanine aminotransferase increased
subjects affected / exposed	7 / 136 (5.15%)	0 / 65 (0.00%)	13 / 231 (5.63%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	10	0	21	4	0	0	0	0	0	0	0
Gamma-glutamyltransferase increased
subjects affected / exposed	7 / 136 (5.15%)	3 / 65 (4.62%)	20 / 231 (8.66%)	5 / 114 (4.39%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	17	3	48	9	0	0	2	0	0	0	0
Weight decreased
subjects affected / exposed	9 / 136 (6.62%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	15	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Fall
subjects affected / exposed	7 / 136 (5.15%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	10	0	0	0	0	0	0	0	0	0	0
Contusion
subjects affected / exposed	10 / 136 (7.35%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	12	0	0	0	0	0	0	0	0	0	0
Cardiac disorders
Atrial fibrillation
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	1 / 16 (6.25%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Palpitations
subjects affected / exposed	14 / 136 (10.29%)	1 / 65 (1.54%)	27 / 231 (11.69%)	4 / 114 (3.51%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	19	1	35	4	0	0	0	0	0	0	0
Tachycardia
subjects affected / exposed	11 / 136 (8.09%)	1 / 65 (1.54%)	14 / 231 (6.06%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	13	1	20	1	0	0	2	0	0	0	0
Nervous system disorders
Neuropathy peripheral
subjects affected / exposed	13 / 136 (9.56%)	4 / 65 (6.15%)	14 / 231 (6.06%)	8 / 114 (7.02%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	17	4	19	9	0	0	2	0	0	0	0
Headache
subjects affected / exposed	52 / 136 (38.24%)	7 / 65 (10.77%)	52 / 231 (22.51%)	14 / 114 (12.28%)	0 / 16 (0.00%)	0 / 13 (0.00%)	5 / 26 (19.23%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	76	12	97	21	0	0	7	0	0	0	0
Dizziness
subjects affected / exposed	26 / 136 (19.12%)	7 / 65 (10.77%)	43 / 231 (18.61%)	9 / 114 (7.89%)	0 / 16 (0.00%)	0 / 13 (0.00%)	4 / 26 (15.38%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	39	14	53	12	0	0	5	0	0	0	0
Amnesia
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	3 / 26 (11.54%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	0	0
Dysgeusia
subjects affected / exposed	12 / 136 (8.82%)	1 / 65 (1.54%)	14 / 231 (6.06%)	3 / 114 (2.63%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	1 / 16 (6.25%)
occurrences all number	13	1	18	3	0	0	0	0	0	0	1
Peripheral sensory neuropathy
subjects affected / exposed	7 / 136 (5.15%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	7	0	0	0	0	0	0	0	0	0	0
Paraesthesia
subjects affected / exposed	11 / 136 (8.09%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	31	1	0	0	0	0	0	0	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	74 / 136 (54.41%)	5 / 65 (7.69%)	111 / 231 (48.05%)	7 / 114 (6.14%)	1 / 16 (6.25%)	0 / 13 (0.00%)	12 / 26 (46.15%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	259	5	328	11	1	0	23	0	0	0	0
Neutropenia
subjects affected / exposed	24 / 136 (17.65%)	3 / 65 (4.62%)	42 / 231 (18.18%)	3 / 114 (2.63%)	0 / 16 (0.00%)	0 / 13 (0.00%)	10 / 26 (38.46%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	77	7	128	14	0	0	19	0	0	0	0
Thrombocytopenia
subjects affected / exposed	73 / 136 (53.68%)	2 / 65 (3.08%)	93 / 231 (40.26%)	4 / 114 (3.51%)	0 / 16 (0.00%)	0 / 13 (0.00%)	13 / 26 (50.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	226	3	256	4	0	0	36	0	0	0	0
Leukopenia
subjects affected / exposed	11 / 136 (8.09%)	4 / 65 (6.15%)	17 / 231 (7.36%)	5 / 114 (4.39%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	38	6	52	17	0	0	0	0	0	0	0
Eye disorders
Dry eye
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	1 / 16 (6.25%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	1	0	0	0	0	0	0
Gastrointestinal disorders
Constipation
subjects affected / exposed	56 / 136 (41.18%)	12 / 65 (18.46%)	96 / 231 (41.56%)	23 / 114 (20.18%)	0 / 16 (0.00%)	0 / 13 (0.00%)	9 / 26 (34.62%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	1 / 16 (6.25%)
occurrences all number	105	14	163	30	0	0	12	0	0	0	1
Ascites
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0
Abdominal pain lower
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0
Abdominal pain
subjects affected / exposed	34 / 136 (25.00%)	17 / 65 (26.15%)	63 / 231 (27.27%)	39 / 114 (34.21%)	0 / 16 (0.00%)	0 / 13 (0.00%)	7 / 26 (26.92%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	50	24	93	50	0	0	8	0	0	0	0
Stomatitis
subjects affected / exposed	5 / 136 (3.68%)	4 / 65 (6.15%)	11 / 231 (4.76%)	7 / 114 (6.14%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	5	4	18	11	0	0	2	0	0	0	0
Flatulence
subjects affected / exposed	7 / 136 (5.15%)	3 / 65 (4.62%)	12 / 231 (5.19%)	9 / 114 (7.89%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	9	3	17	10	0	0	2	0	0	0	0
Nausea
subjects affected / exposed	106 / 136 (77.94%)	23 / 65 (35.38%)	168 / 231 (72.73%)	41 / 114 (35.96%)	0 / 16 (0.00%)	0 / 13 (0.00%)	13 / 26 (50.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	205	46	304	59	0	0	16	0	0	0	0
Diarrhoea
subjects affected / exposed	40 / 136 (29.41%)	15 / 65 (23.08%)	44 / 231 (19.05%)	23 / 114 (20.18%)	1 / 16 (6.25%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	71	28	76	34	2	0	2	0	0	0	0
Vomiting
subjects affected / exposed	57 / 136 (41.91%)	10 / 65 (15.38%)	74 / 231 (32.03%)	21 / 114 (18.42%)	0 / 16 (0.00%)	0 / 13 (0.00%)	10 / 26 (38.46%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	1 / 16 (6.25%)
occurrences all number	96	13	126	31	0	0	11	0	0	0	1
Abdominal pain upper
subjects affected / exposed	17 / 136 (12.50%)	9 / 65 (13.85%)	24 / 231 (10.39%)	9 / 114 (7.89%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	26	12	36	17	0	0	0	0	0	0	0
Abdominal distension
subjects affected / exposed	4 / 136 (2.94%)	6 / 65 (9.23%)	23 / 231 (9.96%)	15 / 114 (13.16%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	6	7	29	17	0	0	0	0	0	0	0
Dyspepsia
subjects affected / exposed	23 / 136 (16.91%)	10 / 65 (15.38%)	22 / 231 (9.52%)	9 / 114 (7.89%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	37	11	25	10	0	0	0	0	0	0	0
Dry mouth
subjects affected / exposed	19 / 136 (13.97%)	2 / 65 (3.08%)	19 / 231 (8.23%)	5 / 114 (4.39%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	38	5	27	6	0	0	0	0	0	0	0
Haemorrhoids
subjects affected / exposed	7 / 136 (5.15%)	2 / 65 (3.08%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	7	2	0	0	0	0	0	0	0	0	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	22 / 231 (9.52%)	4 / 114 (3.51%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	25	4	0	0	0	0	0	0	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	14 / 136 (10.29%)	1 / 65 (1.54%)	16 / 231 (6.93%)	5 / 114 (4.39%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	16	1	20	5	0	0	2	0	0	0	0
Photosensitivity reaction
subjects affected / exposed	11 / 136 (8.09%)	0 / 65 (0.00%)	25 / 231 (10.82%)	1 / 114 (0.88%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	13	0	37	1	0	0	2	0	0	0	0
Petechiae
subjects affected / exposed	9 / 136 (6.62%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	10	0	0	0	0	0	0	0	0	0	0
Pruritus
subjects affected / exposed	12 / 136 (8.82%)	3 / 65 (4.62%)	5 / 231 (2.16%)	8 / 114 (7.02%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	13	3	5	8	0	0	0	0	0	0	0
Alopecia
subjects affected / exposed	15 / 136 (11.03%)	6 / 65 (9.23%)	20 / 231 (8.66%)	8 / 114 (7.02%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	17	6	21	9	0	0	0	0	0	0	0
Dry skin
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	18 / 231 (7.79%)	5 / 114 (4.39%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	30	7	0	0	0	0	0	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	7 / 136 (5.15%)	1 / 65 (1.54%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	11	1	0	0	0	0	0	0	0	0	0
Musculoskeletal and connective tissue disorders
Joint swelling
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	3 / 26 (11.54%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	3	0	0	0	0
Muscle spasms
subjects affected / exposed	16 / 136 (11.76%)	2 / 65 (3.08%)	14 / 231 (6.06%)	5 / 114 (4.39%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	24	2	15	5	0	0	0	0	0	0	0
Pain in extremity
subjects affected / exposed	19 / 136 (13.97%)	4 / 65 (6.15%)	16 / 231 (6.93%)	13 / 114 (11.40%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	27	4	19	14	0	0	0	0	0	0	0
Back pain
subjects affected / exposed	29 / 136 (21.32%)	9 / 65 (13.85%)	33 / 231 (14.29%)	16 / 114 (14.04%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	40	9	38	38	0	0	0	0	0	0	0
Arthralgia
subjects affected / exposed	29 / 136 (21.32%)	10 / 65 (15.38%)	27 / 231 (11.69%)	14 / 114 (12.28%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	44	11	40	20	0	0	0	0	0	0	0
Myalgia
subjects affected / exposed	15 / 136 (11.03%)	6 / 65 (9.23%)	21 / 231 (9.09%)	12 / 114 (10.53%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	18	7	24	13	0	0	0	0	0	0	0
Musculoskeletal pain
subjects affected / exposed	11 / 136 (8.09%)	2 / 65 (3.08%)	12 / 231 (5.19%)	3 / 114 (2.63%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	14	2	23	3	0	0	0	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	8 / 231 (3.46%)	7 / 114 (6.14%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	9	11	0	0	0	0	0	0	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	20 / 136 (14.71%)	6 / 65 (9.23%)	26 / 231 (11.26%)	5 / 114 (4.39%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	25	11	40	5	0	0	2	0	0	0	0
Bronchitis
subjects affected / exposed	6 / 136 (4.41%)	4 / 65 (6.15%)	15 / 231 (6.49%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	8	4	19	2	0	0	0	0	0	0	0
Sinusitis
subjects affected / exposed	10 / 136 (7.35%)	1 / 65 (1.54%)	15 / 231 (6.49%)	2 / 114 (1.75%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	13	1	19	2	0	0	0	0	0	0	0
Upper respiratory tract infection
subjects affected / exposed	15 / 136 (11.03%)	3 / 65 (4.62%)	14 / 231 (6.06%)	4 / 114 (3.51%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	18	5	18	5	0	0	0	0	0	0	0
Nasopharyngitis
subjects affected / exposed	21 / 136 (15.44%)	4 / 65 (6.15%)	29 / 231 (12.55%)	11 / 114 (9.65%)	0 / 16 (0.00%)	0 / 13 (0.00%)	0 / 26 (0.00%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	33	7	40	17	0	0	0	0	0	0	0
Metabolism and nutrition disorders
Decreased appetite
subjects affected / exposed	30 / 136 (22.06%)	9 / 65 (13.85%)	67 / 231 (29.00%)	18 / 114 (15.79%)	1 / 16 (6.25%)	0 / 13 (0.00%)	6 / 26 (23.08%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	49	12	94	22	1	0	6	0	0	0	0
Dehydration
subjects affected / exposed	0 / 136 (0.00%)	0 / 65 (0.00%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	0	0	0	0	0	0	2	0	0	0	0
Hyperglycaemia
subjects affected / exposed	7 / 136 (5.15%)	5 / 65 (7.69%)	0 / 231 (0.00%)	0 / 114 (0.00%)	0 / 16 (0.00%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	8	10	0	0	0	0	2	0	0	0	0
Hypomagnesaemia
subjects affected / exposed	15 / 136 (11.03%)	8 / 65 (12.31%)	18 / 231 (7.79%)	6 / 114 (5.26%)	1 / 16 (6.25%)	0 / 13 (0.00%)	2 / 26 (7.69%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	0 / 16 (0.00%)
occurrences all number	40	18	28	14	1	0	2	0	0	0	0
Hypokalaemia
subjects affected / exposed	11 / 136 (8.09%)	5 / 65 (7.69%)	15 / 231 (6.49%)	4 / 114 (3.51%)	1 / 16 (6.25%)	0 / 13 (0.00%)	4 / 26 (15.38%)	0 / 22 (0.00%)	0 / 8 (0.00%)	0 / 31 (0.00%)	1 / 16 (6.25%)
occurrences all number	14	10	26	5	1	0	5	0	0	0	1

More information

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Were there any global substantial amendments to the protocol? Yes

03 May 2013

Protocol amendment 01: Addition of defined clinical criteria for disease progression, clarification of definition of platinum sensitivity.

09 Apr 2014

Protocol amendment 03: Clarified the following: -assignment of participants to cohort based on Myriad Breast Cancer gene (BRCA) test, -exclusion for immunocompromised participants, -approach to dose modification and discontinuation due to hematologic events. Added Cycle 1 visit for complete blood count (CBC) to allow early detection of hematologic abnormalities

04 Dec 2014

Protocol amendment 04: Addition of centralized homologous recombination deficiency (HRD) testing and associated end points and sample size changes. Clarifying that dose modifications could be made at any time for intolerable toxicity

11 Sep 2015

Protocol amendment 05: Clarification of exclusion criteria of corrected QT interval (QTc)-prolonging medications. Updated guidance on monitoring and following participants for potential risk for myelodysplastic syndrome (MDS)/ acute myeloid leukemia (AML). Clarifying that progression is not considered an adverse event (AE).

09 Mar 2016

Protocol amendment 06: Clarification of HRD+ definition and primary endpoint, addition of secondary objectives, and removal of an interim analysis.

31 May 2017

Protocol amendment 07: Alignment with unblinding standard operating procedure (SOP) and updated standard niraparib safety language for AEs, serious AEs (SAEs), and adverse events of specific interests (AESIs) reporting. Addition of primary analysis data to replace Phase 1 data. Additional guidance for blood pressure monitoring. Introduction of Extended Visit Cycle to minimize participant burden.

29 Jan 2019

Protocol amendment 08: Clarifying survival assessment and decreasing data collection burden in follow-up. Alignment of safety language with updated niraparib risk management plan and General Data Protection Regulation

Were there any global interruptions to the trial? No

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

None reported

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Clinical trials

Clinical Trial Results: A Phase 3 Randomized Double-Blind Trial of Maintenance with Niraparib Versus Placebo in Patients with Platinum Sensitive Ovarian Cancer

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer gene (BRCA) Mutation (gBRCA)

Primary: Progression-Free Survival (PFS) in Cohort With Germline BReast CAncer gene (BRCA) Mutation (gBRCA)

Primary: Progression-Free Survival (PFS) in Cohort with No Germline BCRA with homologous recombination deficiency-positive (HRD+) tumors (non-gBRCAmut HRD+)

Primary: Progression-Free Survival (PFS) in Cohort with No Germline BCRA with homologous recombination deficiency-positive (HRD+) tumors (non-gBRCAmut HRD+)

Primary: Progression-Free Survival (PFS) in Cohort with No Germline BRCA Mutation (non-gBRCA)

Primary: Progression-Free Survival (PFS) in Cohort with No Germline BRCA Mutation (non-gBRCA)

Secondary: Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Time to First Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation

Secondary: Time to First Subsequent Therapy in Cohort With No Germline BRCA Mutation

Secondary: Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Chemotherapy-Free Interval in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Progression-Free Survival 2 in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation

Secondary: Chemotherapy-Free Interval in Cohort With No Germline BRCA Mutation

Secondary: Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation

Secondary: Progression-Free Survival 2 in Cohort With No Germline BRCA Mutation

Secondary: Overall Survival in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Overall Survival in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Time to Second Subsequent Therapy in Cohort With Germline BRCA Mutation (gBRCA)

Secondary: Overall Survival in Cohort With No Germline BRCA Mutation

Secondary: Overall Survival in Cohort With No Germline BRCA Mutation

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 6

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 4

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at Cycle 2

Secondary: Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation

Secondary: Time to Second Subsequent Therapy in Cohort With No Germline BRCA Mutation

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 4

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at post-progression

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With Germline BRCA at post-progression

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 2

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at Cycle 6

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 4

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at Cycle 6

Secondary: Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2

Secondary: Change From Baseline in European Quality of Life Scale, 5-Dimensions (EQ-5D-5L) in Cohort With Germline BRCA at Cycle 2

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at post-progression

Secondary: Change From Baseline in Functional Assessment of Cancer Therapy-Ovarian Symptom Index in Cohort With no Germline BRCA at post-progression

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at post-progression

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at post-progression

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 6

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 4

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at post-progression

Secondary: Change From Baseline in EQ-5D-5L in Cohort With Germline BRCA at post-progression

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2

Secondary: Change From Baseline in EQ-5D-5L in Cohort With no Germline BRCA at Cycle 2

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Baseline

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Baseline

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 2

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 2

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 4

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 4

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 6

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at Cycle 6

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at post-progression

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With Germline BRCA at post-progression

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Baseline

Secondary: Number of participants with response to Neuropathy questionnaire in Cohort With no Germline BRCA at Baseline

Clinical Trial Results:
A Phase 3 Randomized Double-Blind Trial of Maintenance with Niraparib Versus Placebo in Patients with Platinum Sensitive Ovarian Cancer