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Clinical Trial Results:
A phase 3, double-blind, randomized, placebo-controlled study to assess the safety and efficacy of a single oral administration of nolasiban to improve pregnancy rates following In vitro Fertilization (IVF) or Intra-cytoplasmic Sperm Injection (ICSI) in Day 3 and Day 5 fresh embryo transfer cycles (IMPLANT 2)

Summary
EudraCT number	2016-004266-25
Trial protocol	CZ DE DK BE HU EE ES FI PL
Global end of trial date	19 Feb 2019

Results information
Results version number	v1(current)
This version publication date	22 Jan 2020
First version publication date	22 Jan 2020
Other versions

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

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Trial information

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Sponsor protocol code

16-OBE001-005

ISRCTN number

US NCT number

NCT03081208

WHO universal trial number (UTN)

Sponsor organisation name

ObsEva SA

Sponsor organisation address

12 Chemin des Aulx, Plan-Les-Ouates, Switzerland, 1228

Public contact

Clinical Trial Director, ObsEva S.A., 41 0225523840, clinicaltrials@obseva.ch

Scientific contact

Clinical Trial Director, ObsEva S.A., 41 0225523840, clinicaltrials@obseva.ch

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

23 Jan 2019

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

19 Feb 2019

Was the trial ended prematurely?

Main objective of the trial

The primary objective is to confirm the efficacy of a single oral 900 mg dose of nolasiban to increase the ongoing clinical pregnancy rate at 10 weeks post-embryo transfer (ET) day.

Protection of trial subjects

This study was to be performed in accordance with the protocol, with the ethical principles that have their origin in the Declaration of Helsinki, with the International Council for Harmonization (ICH) Harmonized Tripartite Guideline for Good Clinical Practice (GCP), with the European Union Clinical Trial Directive, and with all applicable local laws and regulations. Before initiation of the study at a given site, written approval of the protocol, the Informed Consent Form (ICF), and any information presented to potential subjects had to be obtained from the appropriate Independent Ethics Committee (IEC).

Background therapy

Subjects in this study were undergoing controlled ovarian hyperstimulation (COH) in preparation for IVF/ICSI according to the clinical center’s practice, following a gonadotropin releasing hormone (GnRH) antagonist protocol. Final follicular maturation was to be performed with one administration of human chorionic gonadotropin (hCG), and luteal support was to be provided using vaginal micronized natural P4 at 600 mg daily (or local alternative if not available) starting from the morning after oocyte pick-up (OPU) until at least the Week 6 visit (for subjects with positive pregnancy test at the Week 2 visit).

Evidence for comparator

Actual start date of recruitment

08 Mar 2017

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Number of subjects enrolled per country

Country: Number of subjects enrolled

Poland: 217

Country: Number of subjects enrolled

Spain: 52

Country: Number of subjects enrolled

Belgium: 13

Country: Number of subjects enrolled

Czech Republic: 241

Country: Number of subjects enrolled

Denmark: 43

Country: Number of subjects enrolled

Estonia: 17

Country: Number of subjects enrolled

Finland: 11

Country: Number of subjects enrolled

Germany: 9

Country: Number of subjects enrolled

Hungary: 176

Worldwide total number of subjects

779

EEA total number of subjects

779

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)

779

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

First patient screened: 08Mar2017 Last patient completed: 04Jan2018 Last neonatal follow-up data: 06Sep2018 Last infant follow-up data: 23Jan2019 Study conducted at 43 study sites in 9 countries [Czech Rep (8), Poland (6), Hungary (4), Spain (8), Denmark (4), Belgium (4), Estonia (2), Germany (4) and Finland (3)].

Screening details

A total of 1103 potential subjects were screened, of whom 779 were randomized. One randomized subject who was randomized to nolasiban in the D5 subgroup was found to be ineligible for the study and did not receive study treatment. Consequently, this subject was not included in the Full Analysis Set (FAS). Therefore, the FAS included 778 subject.

Period 1 title

Treatment Period

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst

Blinding implementation details

As soon as the last subject completed the last scheduled visit up to Week 10 and all data up to this visit were entered into the clinical database, cleaned, and locked, the treatment groups were unblinded to the sponsor, and the results up to the Week 10 visit were analyzed and described in a CSR. However Subjects and investigators remained blinded until the end of the 6-month infant follow-up.

Are arms mutually exclusive

Yes

nolasiban 900mg (overall Day 3 and Day 5)

Arm description

A single oral dose of 900 mg nolasiban was administered to the subject at the investigational site about 4 hours prior to the single embryo transfer (SET).

Arm type

Experimental

Investigational medicinal product name

nolasiban

Investigational medicinal product code

OBE001

Other name

Pharmaceutical forms

Dispersible tablet

Routes of administration

Oral use

Dosage and administration details

On the day of SET, subjects received a single oral dose of 900 mg nolasiban dispersed in water approximately 4 hours prior to the transfer procedure.

placebo (overall Day 3 and Day 5)

Arm description

A single oral dose of matching placebo was administered to the subject at the investigational site about 4 hours prior to the SET.

Arm type

Placebo

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet

Routes of administration

Oral use

Dosage and administration details

On the day of SET, subjects received a single oral dose of matching placebo, dispersed in water approximately 4 hours prior to the transfer procedure.

Number of subjects in period 1 ^[1]	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)
Started	388	390
Week 10	388	390
Completed	388	390

Notes
[1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
Justification: Subject 110331 was not treated because she did not meet eligibility criterion no. 9.

Period 2 title

Follow-up Period 1

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Blinding implementation details

As soon as the last subject completed Week 10 and the database was locked, the treatment groups were unblinded to the Sponsor. Subjects and investigators remained blinded until the end of the 6-month infant follow-up period 2

Are arms mutually exclusive

Yes

Follow-up 1 - nolasiban overall Day 3 and Day 5

Arm description

All Women Follow-Up (AWFU) Set: All subjects, treated with nolasiban, who took part in the pregnancy outcome follow-up. This was the analysis set for the analysis of pregnancy outcome data.

Arm type

Experimental

Investigational medicinal product name

nolasiban

Investigational medicinal product code

OBE001

Other name

Pharmaceutical forms

Dispersible tablet

Routes of administration

Oral use

Dosage and administration details

On the day of SET, subjects received a single oral dose of 900 mg nolasiban dispersed in water approximately 4 hours prior to the transfer procedure.

Follow-up 1 - placebo overall Day 3 and Day 5

Arm description

All Women Follow-Up (AWFU) Set: All subjects, receiving placebo, who took part in the pregnancy outcome follow-up. This was the analysis set for the analysis of pregnancy outcome data. Note: Subject 120505 (SET D3, was randomized to nolasiban but received placebo. This subject gave birth to 1 live infant.

Arm type

Placebo

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet

Routes of administration

Oral use

Dosage and administration details

On the day of SET, subjects received a single oral dose of matching placebo, dispersed in water approximately 4 hours prior to the transfer procedure.

Number of subjects in period 2	Follow-up 1 - nolasiban overall Day 3 and Day 5	Follow-up 1 - placebo overall Day 3 and Day 5
Started	388	390
Completed	137	112
Not completed	251	279
Not pregnant	250	279
Transferred to other arm/group	1	-
Joined	0	1
Transferred in from other group/arm	-	1

Period 3 title

Follow-up Period 2

Is this the baseline period?

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor

Blinding implementation details

Are arms mutually exclusive

Yes

Follow-up 2 - nolasiban overall Day 3 and Day 5

Arm description

The AI Analysis Set consists of all infants (whose mothers were treated with nolasiban) assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Arm type

Experimental

Investigational medicinal product name

nolasiban

Investigational medicinal product code

OBE001

Other name

Pharmaceutical forms

Dispersible tablet

Routes of administration

Oral use

Dosage and administration details

On the day of SET, subjects received a single oral dose of 900 mg nolasiban dispersed in water approximately 4 hours prior to the transfer procedure.

Follow-up 2 - placebo overall Day 3 and Day 5

Arm description

The All Infant (AI) Analysis Set consists of all infants (whose mothers received placebo) assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Arm type

Placebo

Investigational medicinal product name

placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Dispersible tablet

Routes of administration

Oral use

Dosage and administration details

On the day of SET, subjects received a single oral dose of matching placebo, dispersed in water approximately 4 hours prior to the transfer procedure.

Number of subjects in period 3	Follow-up 2 - nolasiban overall Day 3 and Day 5	Follow-up 2 - placebo overall Day 3 and Day 5
Started	137	112
Completed	136	109
Not completed	6	5
Pregnancy interruption	1	-
In utero death	-	2
spontaneous abortion	2	-
therapeutic abortion	-	1
Lost to follow-up	3	1
Pregnancy termination	-	1
Joined	5	2
twins	5	2

Baseline characteristics

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Reporting group title

nolasiban 900mg (overall Day 3 and Day 5)

Reporting group description

A single oral dose of 900 mg nolasiban was administered to the subject at the investigational site about 4 hours prior to the single embryo transfer (SET).

Reporting group title

placebo (overall Day 3 and Day 5)

Reporting group description

A single oral dose of matching placebo was administered to the subject at the investigational site about 4 hours prior to the SET.

Reporting group values	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)	Total
Number of subjects	388	390	778
Age categorical
Units: Subjects
Adults (18-64 years)	388	390	778
Not recorded	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	31.1 ± 3.3	31.4 ± 3.2	-
Gender categorical
Units: Subjects
Female	388	390	778

Subject analysis set title

Day 3 Single Embryo Transfer nolasiban

Subject analysis set type

Full analysis

Subject analysis set description

subjects treated with 900 mg nolasiban 4hr before single embryo transfer (SET) on Day 3

Subject analysis set title

Day 3 Single Embryo Transfer placebo

Subject analysis set type

Full analysis

Subject analysis set description

subjects receiving placebo 4hr before single embryo transfer (SET) on Day 3 .

Subject analysis set title

Day 5 Single Embryo Transfer nolasiban

Subject analysis set type

Full analysis

Subject analysis set description

subjects treated with 900 mg nolasiban 4hr before single embryo transfer (SET) on Day 5

Subject analysis set title

Day 5 Single Embryo Transfer placebo

Subject analysis set type

Full analysis

Subject analysis set description

subjects receiving placebo 4hr before single embryo transfer (SET) on Day 5

Subject analysis set title

Safety Analysis: Day 3 Single Embryo Transfer placebo

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: Day 3 Single Embryo Transfer nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: Day 5 Single Embryo Transfer placebo

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: Day 5 Single Embryo Transfer nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: overall Day 3 and Day 5 SET - placebo

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: overall Day 3 and Day 5 SET - nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

AWFU - Day 3 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Day 3 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Overall Day 3 and Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Overall Day 3 and Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-Up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AF - Day 3 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - Day 3 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - overall Day 3 and Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - overall Day 3 and Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AI - Day 3 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - Day 3 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - overall Day 3 and Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - overall Day 3 and Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AIFU - overall Day 3 and Day 5 - nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received nolasiban on either Day 3 or Day 5 Embryo transfers

Subject analysis set title

AIFU - overall Day 3 and Day 5 - placebo

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received placebo on either Day 3 or Day 5 Embryo transfers

Subject analysis set title

AIFU - Day 3 nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received nolasiban on Day 3 Embryo transfer

Subject analysis set title

AIFU - Day 3 placebo

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received placebo on Day 3 Embryo transfer

Subject analysis set title

AIFU - Day 5 nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received nolasiban on Day 5 Embryo transfer

Subject analysis set title

AIFU - Day 5 placebo

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received placebo on Day 5 Embryo transfer

Day 3 Single Embryo Transfer nolasiban

Day 3 Single Embryo Transfer placebo

Day 5 Single Embryo Transfer nolasiban

Day 5 Single Embryo Transfer placebo

Safety Analysis: Day 3 Single Embryo Transfer placebo

Safety Analysis: Day 3 Single Embryo Transfer nolasiban

Safety Analysis: Day 5 Single Embryo Transfer placebo

Safety Analysis: Day 5 Single Embryo Transfer nolasiban

Safety Analysis: overall Day 3 and Day 5 SET - placebo

Safety Analysis: overall Day 3 and Day 5 SET - nolasiban

AWFU - Day 3 SET placebo

AWFU - Day 3 SET nolasiban

AWFU - Day 5 SET placebo

AWFU - Day 5 SET nolasiban

AWFU - Overall Day 3 and Day 5 SET placebo

AWFU - Overall Day 3 and Day 5 SET nolasiban

AF - Day 3 SET placebo

AF - Day 3 SET nolasiban

AF - Day 5 SET placebo

AF - Day 5 SET nolasiban

AF - overall Day 3 and Day 5 SET placebo

AF - overall Day 3 and Day 5 SET nolasiban

AI - Day 3 SET placebo

AI - Day 3 SET nolasiban

AI - Day 5 SET placebo

AI - Day 5 SET nolasiban

AI - overall Day 3 and Day 5 SET placebo

AI - overall Day 3 and Day 5 SET nolasiban

AIFU - overall Day 3 and Day 5 - nolasiban

AIFU - overall Day 3 and Day 5 - placebo

AIFU - Day 3 nolasiban

AIFU - Day 3 placebo

AIFU - Day 5 nolasiban

AIFU - Day 5 placebo

Number of subjects

194

196

195

193

196

194

391

387

112

137

110

136

109

136

124

Units: Subjects

Adults (18-64 years)

194

196

Not recorded

Units: years

arithmetic mean (standard deviation)

31.1 ± 3.2

31.4 ± 3.3

31.1 ± 3.3

31.3 ± 3.2

31.2 ± 3.1

31.1 ± 3.5

31.5 ± 3.4

31.1 ± 3.3

31.4 ± 3.3

31.1 ± 3.3

Units: Subjects

Female

194

196

End points

Top of page

Reporting group title

nolasiban 900mg (overall Day 3 and Day 5)

Reporting group description

A single oral dose of 900 mg nolasiban was administered to the subject at the investigational site about 4 hours prior to the single embryo transfer (SET).

Reporting group title

placebo (overall Day 3 and Day 5)

Reporting group description

A single oral dose of matching placebo was administered to the subject at the investigational site about 4 hours prior to the SET.

Reporting group title

Follow-up 1 - nolasiban overall Day 3 and Day 5

Reporting group description

All Women Follow-Up (AWFU) Set: All subjects, treated with nolasiban, who took part in the pregnancy outcome follow-up. This was the analysis set for the analysis of pregnancy outcome data.

Reporting group title

Follow-up 1 - placebo overall Day 3 and Day 5

Reporting group description

Reporting group title

Follow-up 2 - nolasiban overall Day 3 and Day 5

Reporting group description

The AI Analysis Set consists of all infants (whose mothers were treated with nolasiban) assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Reporting group title

Follow-up 2 - placebo overall Day 3 and Day 5

Reporting group description

The All Infant (AI) Analysis Set consists of all infants (whose mothers received placebo) assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

Day 3 Single Embryo Transfer nolasiban

Subject analysis set type

Full analysis

Subject analysis set description

subjects treated with 900 mg nolasiban 4hr before single embryo transfer (SET) on Day 3

Subject analysis set title

Day 3 Single Embryo Transfer placebo

Subject analysis set type

Full analysis

Subject analysis set description

subjects receiving placebo 4hr before single embryo transfer (SET) on Day 3 .

Subject analysis set title

Day 5 Single Embryo Transfer nolasiban

Subject analysis set type

Full analysis

Subject analysis set description

subjects treated with 900 mg nolasiban 4hr before single embryo transfer (SET) on Day 5

Subject analysis set title

Day 5 Single Embryo Transfer placebo

Subject analysis set type

Full analysis

Subject analysis set description

subjects receiving placebo 4hr before single embryo transfer (SET) on Day 5

Subject analysis set title

Safety Analysis: Day 3 Single Embryo Transfer placebo

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: Day 3 Single Embryo Transfer nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: Day 5 Single Embryo Transfer placebo

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: Day 5 Single Embryo Transfer nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: overall Day 3 and Day 5 SET - placebo

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

Safety Analysis: overall Day 3 and Day 5 SET - nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

The Safety Analysis Set consists of all randomized subjects who received study medication (analyzed by treatment received)

Subject analysis set title

AWFU - Day 3 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Day 3 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Overall Day 3 and Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AWFU - Overall Day 3 and Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Women Follow-Up (AWFU) Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up.

Subject analysis set title

AF - Day 3 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - Day 3 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - overall Day 3 and Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AF - overall Day 3 and Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Fetuses (AF) Set consists of all fetuses for whom data from the Pregnancy Outcome and Neonatal Health form were available.

Subject analysis set title

AI - Day 3 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - Day 3 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - overall Day 3 and Day 5 SET placebo

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AI - overall Day 3 and Day 5 SET nolasiban

Subject analysis set type

Sub-group analysis

Subject analysis set description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Subject analysis set title

AIFU - overall Day 3 and Day 5 - nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received nolasiban on either Day 3 or Day 5 Embryo transfers

Subject analysis set title

AIFU - overall Day 3 and Day 5 - placebo

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received placebo on either Day 3 or Day 5 Embryo transfers

Subject analysis set title

AIFU - Day 3 nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received nolasiban on Day 3 Embryo transfer

Subject analysis set title

AIFU - Day 3 placebo

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received placebo on Day 3 Embryo transfer

Subject analysis set title

AIFU - Day 5 nolasiban

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received nolasiban on Day 5 Embryo transfer

Subject analysis set title

AIFU - Day 5 placebo

Subject analysis set type

Safety analysis

Subject analysis set description

All infants entered into the 6-month infant follow-up (AIFU) whose mothers received placebo on Day 5 Embryo transfer

Primary: Number of women pregnant at 10 weeks post-SET

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End point title

Number of women pregnant at 10 weeks post-SET

End point description

End point type

Primary

End point timeframe

10 weeks after embryo transfer

End point values	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)	Day 3 Single Embryo Transfer nolasiban	Day 3 Single Embryo Transfer placebo	Day 5 Single Embryo Transfer nolasiban	Day 5 Single Embryo Transfer placebo
Number of subjects analysed	388	390	194	194	194	196
Units: number of pregnant women
pregnant at week 10	138	111	49	43	89	68
not pregnant at week 10	250	279	145	151	105	128

OPR 10 Weeks Post-SET – Overall D3/D5: Main Model

Statistical analysis description

Ongoing Pregnancy Rate 10 Weeks Post-SET – Overall D3/D5: Main Model (FAS)

Comparison groups

nolasiban 900mg (overall Day 3 and Day 5) v placebo (overall Day 3 and Day 5)

Number of subjects included in analysis

778

Analysis specification

Pre-specified

Analysis type

other ^[1]

P-value

= 0.031 ^[2]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.43

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

1.99

Notes
[1] - The primary analysis of the primary efficacy endpoint was performed on the overall D3/D5 FAS by fitting an exact logistic regression model with treatment as the independent variable, the day of transfer (SET D3 or SET D5) as a covariate, and the clinical site as a stratum.
[2] - p-value calculated based on exact conditional distribution.

OPR 10 Weeks Post-SET Day 3

Statistical analysis description

Ongoing Pregnancy Rate 10 Weeks Post-SET Day 3 of Embryo Transfer Using the Main Model (FAS)

Comparison groups

Day 3 Single Embryo Transfer nolasiban v Day 3 Single Embryo Transfer placebo

Number of subjects included in analysis

388

Analysis specification

Pre-specified

Analysis type

other ^[3]

P-value

= 0.477 ^[4]

Method

Regression, Linear

Parameter type

Odds ratio (OR)

Point estimate

1.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.96

Notes
[3] - Odds ratio and 95% CI estimated using a stratified exact logistic regression model with fixed effect for treatment group and site as a stratification factor.
[4] - p-value calculated based on exact conditional distribution.

OPR 10 Weeks Post-SET Day 5

Statistical analysis description

Ongoing Pregnancy Rate 10 Weeks Post-SET on Day 5 Embryo of Transfer Using the Main Model (FAS)

Comparison groups

Day 5 Single Embryo Transfer nolasiban v Day 5 Single Embryo Transfer placebo

Number of subjects included in analysis

390

Analysis specification

Pre-specified

Analysis type

other ^[5]

P-value

= 0.034 ^[6]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.59

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

2.47

Notes
[5] - Odds ratio and 95% CI estimated using a stratified exact logistic regression model with fixed effect for treatment group and site as a stratification factor.
[6] - p-value calculated based on exact conditional distribution.

Primary: Percentage of women pregnant at week 10 post-SET

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End point title

Percentage of women pregnant at week 10 post-SET

End point description

Intra-uterine pregnancy with fetal heartbeat at 10 weeks post-SET day.

End point type

Primary

End point timeframe

Pregnant 10 weeks after single embryo transfer (SET)

End point values	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)	Day 3 Single Embryo Transfer nolasiban	Day 3 Single Embryo Transfer placebo	Day 5 Single Embryo Transfer nolasiban	Day 5 Single Embryo Transfer placebo
Number of subjects analysed	388	390	194 ^[7]	194 ^[8]	194 ^[9]	196 ^[10]
Units: percent
number (not applicable)	35.6	28.5	25.3	22.2	45.9	34.7

Notes
[7] - for statistical values see previous table for Day 3 ET
[8] - for statistical values see previous table for Day 3 ET
[9] - for statistical values see previous table for Day 5 ET
[10] - for statistical values see previous table for Day 5 ET

% OPR 10 Weeks Post-SET Day 3

Comparison groups

Day 3 Single Embryo Transfer nolasiban v Day 3 Single Embryo Transfer placebo

Number of subjects included in analysis

388

Analysis specification

Pre-specified

Analysis type

other ^[11]

P-value

= 0.477

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.19

Confidence interval

level

95%

sides

2-sided

lower limit

0.73

upper limit

1.96

Notes
[11] - Separate exact logistic regression models for the SET D3 and the SET D5 transfer groups were also performed. The ongoing pregnancy rate 10 weeks post-SET by day of transfer is presented for the FAS. This analysis uses a similar stratified exact logistic regression analysis except that day is no longer a covariate since SET D3 and SET D5 are analyzed separately.

% OPR 10 Weeks Post-SET Day 5

Statistical analysis description

Separate exact logistic regression models for the SET D3 and the SET D5 transfer groups were also performed. The ongoing pregnancy rate 10 weeks post-SET by day of transfer is presented for the FAS. This analysis uses a similar stratified exact logistic regression analysis except that day is no longer a covariate since SET D3 and SET D5 are analyzed separately.

Comparison groups

Day 5 Single Embryo Transfer nolasiban v Day 5 Single Embryo Transfer placebo

Number of subjects included in analysis

390

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.034

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.59

Confidence interval

level

95%

sides

2-sided

lower limit

1.02

upper limit

2.47

Secondary: Number of Live births after 24 weeks of gestation

Top of page

End point title

Number of Live births after 24 weeks of gestation

End point description

All subjects who took part in the pregnancy outcome follow-up, analyzed according to treatment received (used for the analysis of pregnancy outcome data for the subjects).

End point type

Secondary

End point timeframe

After 24 weeks of gestation

End point values	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)	Day 3 Single Embryo Transfer nolasiban	Day 3 Single Embryo Transfer placebo	Day 5 Single Embryo Transfer nolasiban	Day 5 Single Embryo Transfer placebo
Number of subjects analysed	388	390	194	194	194	196
Units: Number of live births
Live Birth Rate - YES	135	108	48	43	87	65
Live birth Rate - NO	253	282	146	151	107	131

Live Birth Rate - Overall D3/D5

Statistical analysis description

Key Secondary Efficacy Endpoint: Live Birth Rate – Loss to Follow- Up Assigned as a Positive Response (FAS). (Results assuming a negative response in case of loss to follow-up were consistent with those assuming a positive response in case of loss to follow-up. A total of 4 subjects were lost to follow-up, 1 in the placebo group and 3 in the nolasiban group; consequently, differences between the analyses using different imputation methods for these subjects were minimal)

Comparison groups

nolasiban 900mg (overall Day 3 and Day 5) v placebo (overall Day 3 and Day 5)

Number of subjects included in analysis

778

Analysis specification

Pre-specified

Analysis type

other ^[12]

P-value

= 0.025 ^[13]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.44

Confidence interval

level

95%

sides

2-sided

lower limit

1.03

upper limit

Notes
[12] - The key secondary efficacy endpoint was performed on the overall D3/D5 FAS by fitting an exact logistic regression model with treatment as the independent variable, the day of transfer (SET D3 or SET D5) as a covariate, and the clinical site as a stratum.
[13] - p-value calculated based on exact conditional distribution.

Live Birth Rate - D3 only

Statistical analysis description

Day 3 only Embryo transfer

Comparison groups

Day 3 Single Embryo Transfer nolasiban v Day 3 Single Embryo Transfer placebo

Number of subjects included in analysis

388

Analysis specification

Pre-specified

Analysis type

other ^[14]

P-value

= 0.552 ^[15]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.16

Confidence interval

level

95%

sides

2-sided

lower limit

0.71

upper limit

1.91

Notes
[14] - Odds ratio and 95% CI estimated using logistic regression model with fixed effects for treatment group and site as a stratification factor.
[15] - p-value calculated based on exact conditional distribution.

Live Birth Rate - D5 only

Comparison groups

Day 5 Single Embryo Transfer nolasiban v Day 5 Single Embryo Transfer placebo

Number of subjects included in analysis

390

Analysis specification

Pre-specified

Analysis type

other ^[16]

P-value

= 0.025 ^[17]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

1.64

Confidence interval

level

95%

sides

2-sided

lower limit

1.05

upper limit

2.56

Notes
[16] - Day 5 only embryo transfer
[17] - p-value calculated based on exact conditional distribution.

Secondary: Percentage of Live Birth after 24 weeks gestation

Top of page

End point title

Percentage of Live Birth after 24 weeks gestation

End point description

End point type

Secondary

End point timeframe

After 24 weeks gestation

End point values	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)	Day 3 Single Embryo Transfer nolasiban	Day 3 Single Embryo Transfer placebo	Day 5 Single Embryo Transfer nolasiban	Day 5 Single Embryo Transfer placebo
Number of subjects analysed	388	390	194 ^[18]	194 ^[19]	194 ^[20]	196 ^[21]
Units: Percentage of live birth
number (not applicable)
Live Birth Rate -YES	34.8	27.7	24.7	22.2	44.8	33.2
Live Birth Rate - NO	65.2	72.3	75.3	77.8	55.2	66.8

Notes
[18] - for statistical values see previous table for Day 3 ET
[19] - for statistical values see previous table for Day 3 ET
[20] - for statistical values see previous table for Day 5 ET
[21] - for statistical values see previous table for Day 5 ET

No statistical analyses for this end point

Secondary: Miscarriage Rate between Week 10 and Week 24 gestation

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End point title

Miscarriage Rate between Week 10 and Week 24 gestation

End point description

A miscarriage was defined as any pregnancy loss prior to 24 weeks. In the overall D3/D5 group and the SET D5 subgroup, rates of miscarriage between Week 2 and Week 24 were numerically lower for nolasiban than for placebo (23% vs. 30% and 18% vs. 28% respectively); treatment difference was less evident in the SET D3 subgroup (30% for nolasiban vs. 34% for placebo).

End point type

Secondary

End point timeframe

Miscarriages reported in this table are those occurring post-Week 10 database lock.

End point values	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)	Day 3 Single Embryo Transfer nolasiban	Day 3 Single Embryo Transfer placebo	Day 5 Single Embryo Transfer nolasiban	Day 5 Single Embryo Transfer placebo
Number of subjects analysed	388 ^[22]	390 ^[23]	194	194	194	196
Units: Number of miscarriages
No. of Subjects pregnant at Wk 2	175	155	69	65	106	90
Miscarriages between W10 and W24 - YES	3	3	1	0	2	3
Miscarriages between W10 and W24 - NO	172	152	68	65	104	87
Total Miscarriages from W2 to W24 - YES	40	47	21	22	19	25
Total Miscarriages from W2 to W24 - NO	135	108	48	43	87	65

Notes
[22] - For miscarriage rates, the denominator is the number of subjects deemed pregnant at 14 days
[23] - For miscarriage rates, the denominator is the number of subjects deemed pregnant at 14 days

No statistical analyses for this end point

Secondary: Neonatal outcomes - AI Set

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End point title

Neonatal outcomes - AI Set

End point description

Analysis of neonatal health data: Overall, 116 (47%) infants were male and 129 (53%) were female (nolasiban: 67 [49%] and 69 [51%]; placebo: 49 [45%] and 60 [55%]). Mean (standard deviation [SD]) gestational age at birth: 38.20 (2.82) wks in nolasiban group and 38.75 (1.92) wks in placebo group. At delivery, mean (SD) weight: 3136.9 (689.7) g in nolasiban group and 3173.9 (517.2) g in placebo group; mean (SD) height: 50.44 (4.55) cm in nolasiban group and 50.88 (3.74) cm in placebo group; and mean (SD) head circumference: 33.70 (2.19) cm in nolasiban group and 34.29 (1.56) cm in placebo group. Mean (SD) Apgar scores: 9.01 (1.50) in nolasiban group and 9.09 (1.28) in placebo group at 1 min, and 9.61 (0.84) and 9.65 (0.76) respectively at 5 mins. Congenital anomalies were present at birth in 5 (4%) infants in nolasiban group and in 4 (4%) in placebo group. Neonatal illnesses were present in 14 (10%) infants in nolasiban group compared to 26 (24%) in placebo

End point type

Secondary

End point timeframe

All Infants (AI) Set: AIs assessed at birth and/or at least 28 days post-delivery and/or who had AEs recorded.

End point values	Follow-up 1 - nolasiban overall Day 3 and Day 5	Follow-up 1 - placebo overall Day 3 and Day 5
Number of subjects analysed	136	109
Units: Number of infants
Sex - Male	67	49
Sex - Female	69	60
Congenital anomaly (at delivery)	5	4
Neonatal illness (at delivery)	14	26
Breastfeeding (at least 28 days after delivery)	111	91
Admission to intensive care at least 28d post-del	9	9
neonatal morbidities - at least 28d post-del	26	29
jaundice	18	20
respiratory distress syndrome	8	10
difficulty in breathing	11	2
difficulty in thermoregulation	6	0
bronchopulmonary dysplasia	3	0

No statistical analyses for this end point

Other pre-specified: Ages and Stages Questionnaires (ASQ-3) Abnormal Scores

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End point title

Ages and Stages Questionnaires (ASQ-3) Abnormal Scores

End point description

Subjects were invited to complete the Ages and Stages Questionnaire-3 (ASQ-3) at 6 months after birth, corrected for gestational age at birth (i.e., at 6 months after the expected term date). Abnormal scores were defined in the ASQ-3 User Guide as domain scores below the following cut-offs: 29.65 points for communication, 25.14 points for fine motor, 22.25 points for gross motor, 25.34 points for personal-social, and 27.72 points for problem-solving.

End point type

Other pre-specified

End point timeframe

To evaluate infant development outcomes 6 months after birth

End point values	AIFU - overall Day 3 and Day 5 - nolasiban	AIFU - overall Day 3 and Day 5 - placebo	AIFU - Day 3 nolasiban	AIFU - Day 3 placebo	AIFU - Day 5 nolasiban	AIFU - Day 5 placebo
Number of subjects analysed	103 ^[24]	88 ^[25]	38	35 ^[26]	65 ^[27]	53 ^[28]
Units: Number of infants below the cut-off
Communication	2	0	1	0	1	0
Fine Motor	19	18	7	8	12	10
Gross Motor	21	20	10	8	11	12
Personal-Social	17	9	5	4	12	5
Problem-Solving	12	3	1	2	11	1
Overall	43	33	14	13	29	20

Notes
[24] - 101 subjects for Personal-Social
[25] - 87 subjects: Communication + Gross Motor 86 subjects: Problem-Solving 85 subjects: Fine Motor
[26] - 34 subjects: Communication 33 subjects: Problem-Solving
[27] - 63 subjects: Personal-Social
[28] - 52 subjects: Gross Motor 50 subjects: Fine Motor

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

TEAEs occurring in subjects or fetuses from the day of study drug administration until 28 days after delivery

Adverse event reporting additional description

AEs were collected up to 4 wks after last visit date or after date of discontinuation. SAEs in relation to pregnancy + birth were reported until end of study. In case of early study discontinuation, any SAEs were reported up to 4 wks post-treatment admin or up to last study visit, should discontinuation occur after 4 wk post-treatment period

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.0

Reporting group title

nolasiban 900mg (overall Day 3 and Day 5)

Reporting group description

A single oral dose of 900 mg nolasiban was administered to the subject at the investigational site about 4 hours prior to the single embryo transfer (SET).

Reporting group title

placebo (overall Day 3 and Day 5)

Reporting group description

A single oral dose of matching placebo was administered to the subject at the investigational site about 4 hours prior to the SET.

Reporting group title

SET Day 5 - nolasiban

Reporting group description

Reporting group title

SET Day 5 - placebo

Reporting group description

Reporting group title

SET Day 3 - nolasiban

Reporting group description

Reporting group title

SET Day 3 - placebo

Reporting group description

Reporting group title

All Women Follow-up Set - overall Day 3 and Day 5 - nolasiban

Reporting group description

AWFU Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up

Reporting group title

All Women Follow-up Set - overall Day 3 and Day 5 - placebo

Reporting group description

AWFU Set consists of all subjects who took part in the pregnancy outcome follow-up, including the 4 subjects who were lost to follow-up

Reporting group title

All infant set - overall Day 3 and Day 5 - nolasiban

Reporting group description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Reporting group title

All infant set - overall Day 3 and Day 5 - placebo

Reporting group description

The All Infant (AI) Analysis Set consists of all infants assessed at birth and/or at least 28 days post-delivery and/or who had adverse events recorded.

Serious adverse events	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)	SET Day 5 - nolasiban	SET Day 5 - placebo	SET Day 3 - nolasiban	SET Day 3 - placebo	All Women Follow-up Set - overall Day 3 and Day 5 - nolasiban	All Women Follow-up Set - overall Day 3 and Day 5 - placebo	All infant set - overall Day 3 and Day 5 - nolasiban	All infant set - overall Day 3 and Day 5 - placebo
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 387 (1.03%)	9 / 391 (2.30%)	2 / 194 (1.03%)	7 / 196 (3.57%)	2 / 193 (1.04%)	2 / 195 (1.03%)	5 / 137 (3.65%)	5 / 112 (4.46%)	6 / 136 (4.41%)	5 / 109 (4.59%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Anaesthetic complication pulmonary
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital, familial and genetic disorders
Trisomy 13
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Turner's syndrome
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Foetal growth restriction
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
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
Atrioventricular septal defect
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
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
Choledochal cyst
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
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
Congenital foot malformation
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	1 / 109 (0.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Congenital genital malformation female
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	1 / 109 (0.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cryptorchism
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	1 / 109 (0.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Heart disease congenital
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
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
Polydactyly
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	1 / 109 (0.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Renal aplasia
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
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
Ventricular septal defect
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
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
Surgical and medical procedures
Abortion induced
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Ectopic pregnancy
subjects affected / exposed	1 / 387 (0.26%)	4 / 391 (1.02%)	0 / 194 (0.00%)	3 / 196 (1.53%)	1 / 193 (0.52%)	1 / 195 (0.51%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 4	0 / 0	0 / 3	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Abortion spontaneous
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	2 / 137 (1.46%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 2	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian hyperstimulation syndrome
subjects affected / exposed	2 / 387 (0.52%)	0 / 391 (0.00%)	2 / 194 (1.03%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	2 / 137 (1.46%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0	0 / 2	0 / 0	0 / 0	0 / 0	0 / 2	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
Adnexal torsion
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Uterine malposition
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain lower
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Meconium ileus
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
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
Infections and infestations
Appendicitis
subjects affected / exposed	0 / 387 (0.00%)	2 / 391 (0.51%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 2	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchiolitis
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	1 / 109 (0.92%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
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

Frequency threshold for reporting non-serious adverse events: 0%

Non-serious adverse events	nolasiban 900mg (overall Day 3 and Day 5)	placebo (overall Day 3 and Day 5)	SET Day 5 - nolasiban	SET Day 5 - placebo	SET Day 3 - nolasiban	SET Day 3 - placebo	All Women Follow-up Set - overall Day 3 and Day 5 - nolasiban	All Women Follow-up Set - overall Day 3 and Day 5 - placebo	All infant set - overall Day 3 and Day 5 - nolasiban	All infant set - overall Day 3 and Day 5 - placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	97 / 387 (25.06%)	101 / 391 (25.83%)	61 / 194 (31.44%)	56 / 196 (28.57%)	36 / 193 (18.65%)	45 / 195 (23.08%)	46 / 137 (33.58%)	43 / 112 (38.39%)	3 / 136 (2.21%)	1 / 109 (0.92%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0
Vascular disorders
Hypertension
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	2	0	0	0	2	0	0	0	0
Vasodilatation
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Extremity necrosis
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Surgical and medical procedures
Oocyte harvest
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Cervix cerclage procedure
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Abortion induced
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Pregnancy, puerperium and perinatal conditions
Biochemical pregnancy
subjects affected / exposed	13 / 387 (3.36%)	21 / 391 (5.37%)	5 / 194 (2.58%)	9 / 196 (4.59%)	8 / 193 (4.15%)	12 / 195 (6.15%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	13	21	5	9	8	12	0	0	0	0
Abortion missed
subjects affected / exposed	19 / 387 (4.91%)	9 / 391 (2.30%)	11 / 194 (5.67%)	6 / 196 (3.06%)	8 / 193 (4.15%)	3 / 195 (1.54%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	19	9	11	6	8	3	0	1	0	0
Abortion spontaneous
subjects affected / exposed	6 / 387 (1.55%)	14 / 391 (3.58%)	1 / 194 (0.52%)	6 / 196 (3.06%)	5 / 193 (2.59%)	8 / 195 (4.10%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	6	14	1	6	5	8	0	0	0	0
Haemorrhage in pregnancy
subjects affected / exposed	4 / 387 (1.03%)	5 / 391 (1.28%)	3 / 194 (1.55%)	2 / 196 (1.02%)	1 / 193 (0.52%)	3 / 195 (1.54%)	4 / 137 (2.92%)	3 / 112 (2.68%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	5	5	3	2	2	3	5	3	0	0
Abortion threatened
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	1 / 137 (0.73%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	0	0	1	1	1	0	0
Blighted ovum
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	1	0	0	0	0	0	0
Abortion incomplete
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0
Imminent abortion
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Subchorionic haematoma
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	2	0	2	0	0	0	2	0	0
Vomiting in pregnancy
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Foetal growth restriction
subjects affected / exposed	2 / 387 (0.52%)	0 / 391 (0.00%)	2 / 194 (1.03%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	2 / 137 (1.46%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	2	0	2	0	0	0	2	0	0	0
Placenta praevia
subjects affected / exposed	5 / 387 (1.29%)	2 / 391 (0.51%)	4 / 194 (2.06%)	1 / 196 (0.51%)	1 / 193 (0.52%)	1 / 195 (0.51%)	5 / 137 (3.65%)	2 / 112 (1.79%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	5	2	4	1	1	1	5	2	0	0
Polyhydramnios
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0
Cervical incompetence
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Premature separation of placenta
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0
Threatened labour
subjects affected / exposed	1 / 387 (0.26%)	2 / 391 (0.51%)	1 / 194 (0.52%)	1 / 196 (0.51%)	0 / 193 (0.00%)	1 / 195 (0.51%)	1 / 137 (0.73%)	2 / 112 (1.79%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	2	1	1	0	1	1	2	0	0
General disorders and administration site conditions
Asthenia
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Feeling hot
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Pain
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Immune system disorders
Drug hypersensitivity
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Reproductive system and breast disorders
Vaginal haemorrhage
subjects affected / exposed	9 / 387 (2.33%)	12 / 391 (3.07%)	7 / 194 (3.61%)	7 / 196 (3.57%)	2 / 193 (1.04%)	5 / 195 (2.56%)	5 / 137 (3.65%)	9 / 112 (8.04%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	9	17	7	11	2	6	5	12	0	0
Ovarian hyperstimulation syndrome
subjects affected / exposed	2 / 387 (0.52%)	4 / 391 (1.02%)	1 / 194 (0.52%)	2 / 196 (1.02%)	1 / 193 (0.52%)	2 / 195 (1.03%)	2 / 137 (1.46%)	4 / 112 (3.57%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	4	4	2	2	2	2	4	4	0	0
Pelvic pain
subjects affected / exposed	4 / 387 (1.03%)	4 / 391 (1.02%)	2 / 194 (1.03%)	3 / 196 (1.53%)	2 / 193 (1.04%)	1 / 195 (0.51%)	2 / 137 (1.46%)	3 / 112 (2.68%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	5	5	2	4	3	1	2	3	0	0
Uterine pain
subjects affected / exposed	2 / 387 (0.52%)	4 / 391 (1.02%)	1 / 194 (0.52%)	4 / 196 (2.04%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	2	4	1	4	1	0	1	1	0	0
Dysmenorrhoea
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Dyspareunia
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Haematosalpinx
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0
Uterine haematoma
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0
Uterine haemorrhage
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	1 / 195 (0.51%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	0	0	1	1	1	0	0	0
Vulvovaginal pruritus
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0
Investigations
Blood triglycerides increased
subjects affected / exposed	2 / 387 (0.52%)	1 / 391 (0.26%)	2 / 194 (1.03%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	2 / 137 (1.46%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	2	1	2	0	0	1	2	0	0	0
Heart rate increased
subjects affected / exposed	1 / 387 (0.26%)	2 / 391 (0.51%)	1 / 194 (0.52%)	1 / 196 (0.51%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	2	1	1	0	1	0	1	0	0
Alanine aminotransferase increased
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Aspartate aminotransferase increased
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Blood alkaline phosphatase increased
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
White blood cells urine positive
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0
Oxygen saturation decreased
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	1 / 109 (0.92%)
occurrences all number	0	0	0	0	0	0	0	0	0	1
Gamma-glutamyltransferase increased
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Injury, poisoning and procedural complications
Post procedural haemorrhage
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Procedural pain
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Congenital, familial and genetic disorders
Patent ductus arteriosus
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Ankyloglossia congenital
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Cardiac disorders
Palpitations
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	11 / 387 (2.84%)	11 / 391 (2.81%)	7 / 194 (3.61%)	4 / 196 (2.04%)	4 / 193 (2.07%)	7 / 195 (3.59%)	5 / 137 (3.65%)	8 / 112 (7.14%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	13	14	9	5	4	9	6	11	0	0
Dizziness
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	0	0	1	0	0	0	0
Disturbance in attention
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Somnolence
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	3 / 387 (0.78%)	6 / 391 (1.53%)	2 / 194 (1.03%)	5 / 196 (2.55%)	1 / 193 (0.52%)	1 / 195 (0.51%)	2 / 137 (1.46%)	4 / 112 (3.57%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	3	6	2	5	1	1	2	4	0	0
Vomiting
subjects affected / exposed	1 / 387 (0.26%)	2 / 391 (0.51%)	1 / 194 (0.52%)	2 / 196 (1.02%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	2 / 112 (1.79%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	2	1	2	0	0	1	2	0	0
Abdominal pain
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	0	0	1	1	0	0	0
Dyspepsia
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	1	0	0	1	1	0	0
Flatulence
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	1 / 137 (0.73%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	0	0	1	1	1	0	0
Abdominal discomfort
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	2	0	2	0	0	0	2	0	0	0
Constipation
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Diarrhoea
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Gastrointestinal pain
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Abdominal pain lower
subjects affected / exposed	0 / 387 (0.00%)	2 / 391 (0.51%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	2 / 112 (1.79%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	2	0	1	0	1	0	2	0	0
Hepatobiliary disorders
Cholestasis of pregnancy
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0
Cholestasis
subjects affected / exposed	1 / 387 (0.26%)	2 / 391 (0.51%)	1 / 194 (0.52%)	1 / 196 (0.51%)	0 / 193 (0.00%)	1 / 195 (0.51%)	1 / 137 (0.73%)	2 / 112 (1.79%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	2	1	1	0	1	1	2	0	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0
Urticaria
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Decubitus ulcer
subjects affected / exposed	0 / 387 (0.00%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	1 / 136 (0.74%)	0 / 109 (0.00%)
occurrences all number	0	0	0	0	0	0	0	0	1	0
Renal and urinary disorders
Cystitis noninfective
subjects affected / exposed	0 / 387 (0.00%)	2 / 391 (0.51%)	0 / 194 (0.00%)	2 / 196 (1.02%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	2 / 112 (1.79%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	2	0	2	0	0	0	2	0	0
Endocrine disorders
Hypothyroidism
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0
Musculoskeletal and connective tissue disorders
Groin pain
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0
Musculoskeletal chest pain
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Neck pain
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	0	0	0
Spinal pain
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Infections and infestations
Urinary tract infection
subjects affected / exposed	3 / 387 (0.78%)	1 / 391 (0.26%)	3 / 194 (1.55%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	2 / 137 (1.46%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	3	1	3	1	0	0	2	1	0	0
Cystitis
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	1	0	0	1	1	0	0
Upper respiratory tract infection
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	1	0	0	1	1	0	0
Herpes virus infection
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0
Otitis media
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0
Vaginal infection
subjects affected / exposed	2 / 387 (0.52%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	2 / 193 (1.04%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	2	0	0	0	2	0	1	0	0	0
Viral upper respiratory tract infection
subjects affected / exposed	1 / 387 (0.26%)	1 / 391 (0.26%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	1 / 137 (0.73%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	1	1	0	0	1	1	1	0	0
Vulvovaginal mycotic infection
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0
Sinusitis
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	0 / 194 (0.00%)	0 / 196 (0.00%)	1 / 193 (0.52%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	0	0	1	0	1	0	0	0
Escherichia infection
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Bacterial vaginosis
subjects affected / exposed	1 / 387 (0.26%)	0 / 391 (0.00%)	1 / 194 (0.52%)	0 / 196 (0.00%)	0 / 193 (0.00%)	0 / 195 (0.00%)	1 / 137 (0.73%)	0 / 112 (0.00%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	1	0	1	0	0	0	1	0	0	0
Urinary tract infection bacterial
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	0 / 196 (0.00%)	0 / 193 (0.00%)	1 / 195 (0.51%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	0	0	1	0	1	0	0
Vulvovaginal candidiasis
subjects affected / exposed	0 / 387 (0.00%)	1 / 391 (0.26%)	0 / 194 (0.00%)	1 / 196 (0.51%)	0 / 193 (0.00%)	0 / 195 (0.00%)	0 / 137 (0.00%)	1 / 112 (0.89%)	0 / 136 (0.00%)	0 / 109 (0.00%)
occurrences all number	0	1	0	1	0	0	0	1	0	0

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Were there any global substantial amendments to the protocol? No

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.

Of 778 subjects treated, 249 had confirmed pregnancies at Wk 10. Follow-up (fu) data were provided for 246 fetuses. Pregnancies resulted in live birth for 243 subjects, assuming +ve outcome in case of loss to fu. Neonatal fu data on 245 infants.

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Clinical trials

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of women pregnant at 10 weeks post-SET

Primary: Number of women pregnant at 10 weeks post-SET

Primary: Percentage of women pregnant at week 10 post-SET

Primary: Percentage of women pregnant at week 10 post-SET

Secondary: Number of Live births after 24 weeks of gestation

Secondary: Number of Live births after 24 weeks of gestation

Secondary: Percentage of Live Birth after 24 weeks gestation

Secondary: Percentage of Live Birth after 24 weeks gestation

Secondary: Miscarriage Rate between Week 10 and Week 24 gestation

Secondary: Miscarriage Rate between Week 10 and Week 24 gestation

Secondary: Neonatal outcomes - AI Set

Secondary: Neonatal outcomes - AI Set

Other pre-specified: Ages and Stages Questionnaires (ASQ-3) Abnormal Scores

Other pre-specified: Ages and Stages Questionnaires (ASQ-3) Abnormal Scores

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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