Trial Outcomes & Findings for Efficacy Study of a Cervical Pessary Containing Progesterone for the Prevention of Preterm Delivery (NCT NCT02225353)

NCT ID: NCT02225353

Last Updated: 2018-10-23

Results Overview

To assess the efficacy of Cerclage Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous parturition before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted between weeks 16 and 24 and removed at 36 weeks and 6 days in pregnant women at high risk of premature delivery. For the purpose of this analysis, pregnancies were no longer considered as high risk for the event if delivery occurred at week 34 of gestation and beyond. Gestational age was determined by the last menstruation date and were confirmed by measurement of the craniocaudal length obtained in the first trimester ultrasound, or by measurement of the cephalic circumference in the second trimester ultrasound predominating the actual date of the last menstrual period. The number of participants not giving birth before 32 weeks and 34 weeks are reported.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 271 participants
• Primary outcome timeframe: Up to 36 weeks of gestational age
• Results posted on: 2018-10-23

Participant Flow

The trial started on 02 Sep 2013 with the enrollment of the first participant and was completed on 13 Mar 2017 when the last participant completed the last follow-up examination according to the protocol. 271 participants signed and informed consent. All 271 were randomized and treated.

Participant milestones

Measure	Progesterone Cervical Pessary (6.3 g) Cervical Pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant at risk of preterm birth and remains installed with no further intervention except at the time of removal.	Progesterone Cervical Pessary (7.7 g) Cervical Pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant at risk of preterm birth and remains installed with no further intervention except at the time of removal.	Progesterone 200 mg Vaginal Capsules Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Overall Study STARTED	91	90	90
Overall Study COMPLETED	87	84	75
Overall Study NOT COMPLETED	4	6	15

Reasons for withdrawal

Measure	Progesterone Cervical Pessary (6.3 g) Cervical Pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant at risk of preterm birth and remains installed with no further intervention except at the time of removal.	Progesterone Cervical Pessary (7.7 g) Cervical Pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant at risk of preterm birth and remains installed with no further intervention except at the time of removal.	Progesterone 200 mg Vaginal Capsules Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Overall Study Lost to Follow-up	0	1	3
Overall Study Protocol Violation	4	5	12

Baseline Characteristics

Efficacy Study of a Cervical Pessary Containing Progesterone for the Prevention of Preterm Delivery

Baseline characteristics by cohort

Measure	Progesterone Cervical Pessary (6.3 g) n=91 Participants Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.	Progesterone Cervical Pessary (7.7 g) n=90 Participants Cervical pessary (PCP) with sustained release of progesterone. The PCP is inserted by investigator to participant (at risk of preterm birth) and remains installed with no further intervention except at the time of removal.	Progesterone 200 mg Vaginal Capsules n=90 Participants Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.	Total n=271 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	91 Participants n=93 Participants	90 Participants n=4 Participants	90 Participants n=27 Participants	271 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Continuous	27.57 years STANDARD_DEVIATION 6.50 • n=93 Participants	27.60 years STANDARD_DEVIATION 6.20 • n=4 Participants	28.18 years STANDARD_DEVIATION 5.16 • n=27 Participants	27.78 years STANDARD_DEVIATION 5.97 • n=483 Participants
Sex: Female, Male Female	91 Participants n=93 Participants	90 Participants n=4 Participants	90 Participants n=27 Participants	271 Participants n=483 Participants
Sex: Female, Male Male	NA Participants n=93 Participants	NA Participants n=4 Participants	NA Participants n=27 Participants	NA Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) White	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	91 Participants n=93 Participants	90 Participants n=4 Participants	90 Participants n=27 Participants	271 Participants n=483 Participants
Region of Enrollment Chile	91 participants n=93 Participants	90 participants n=4 Participants	90 participants n=27 Participants	271 participants n=483 Participants
Height	1.57 meter STANDARD_DEVIATION 0.06 • n=93 Participants	1.58 meter STANDARD_DEVIATION 0.06 • n=4 Participants	1.58 meter STANDARD_DEVIATION 0.05 • n=27 Participants	1.58 meter STANDARD_DEVIATION 0.05 • n=483 Participants
Weight	66.65 kilogram STANDARD_DEVIATION 13.36 • n=93 Participants	71.26 kilogram STANDARD_DEVIATION 14.06 • n=4 Participants	70.62 kilogram STANDARD_DEVIATION 12.73 • n=27 Participants	69.50 kilogram STANDARD_DEVIATION 13.50 • n=483 Participants
Body Mass Index (BMI)	27.03 kilogram per square meter STANDARD_DEVIATION 4.92 • n=93 Participants	28.61 kilogram per square meter STANDARD_DEVIATION 5.45 • n=4 Participants	28.23 kilogram per square meter STANDARD_DEVIATION 4.56 • n=27 Participants	27.95 kilogram per square meter STANDARD_DEVIATION 5.01 • n=483 Participants
Medical History - Prior Preterm Birth	55 Participants n=93 Participants	55 Participants n=4 Participants	50 Participants n=27 Participants	160 Participants n=483 Participants
Medical History - Prior Pregnancy Premature Rupture of Membrane	24 Participants n=93 Participants	20 Participants n=4 Participants	17 Participants n=27 Participants	61 Participants n=483 Participants

PRIMARY outcome

Timeframe: Up to 36 weeks of gestational age

Population: 271 participants comprised the Intention-to-treat analysis (ITT) population at baseline, 268 participants at gestation week 32, and 262 participants at gestation week 34.

To assess the efficacy of Cerclage Pessaries containing 6.3 g and 7.7 g micronized progesterone for the prevention of preterm delivery, established through spontaneous parturition before gestation weeks 32 (31 weeks and 6 days) and 34 (33 weeks and 6 days), when the pessary is inserted between weeks 16 and 24 and removed at 36 weeks and 6 days in pregnant women at high risk of premature delivery.

For the purpose of this analysis, pregnancies were no longer considered as high risk for the event if delivery occurred at week 34 of gestation and beyond. Gestational age was determined by the last menstruation date and were confirmed by measurement of the craniocaudal length obtained in the first trimester ultrasound, or by measurement of the cephalic circumference in the second trimester ultrasound predominating the actual date of the last menstrual period.

The number of participants not giving birth before 32 weeks and 34 weeks are reported.

Outcome measures

Measure	Progesterone Cervical Pessary (6.3 g) n=91 Participants Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.	Progesterone Cervical Pessary (7.7 g) n=90 Participants Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.	Progesterone 200 mg Vaginal Capsules n=90 Participants Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation No birth before 32 weeks	73 Participants	71 Participants	67 Participants
Number of Participants Not Giving Birth Before Week 32 and Week 34 of Gestation No birth before 34 weeks	66 Participants	64 Participants	61 Participants

SECONDARY outcome

Timeframe: Up to 36 weeks of gestational age

Population: Intention-to-Treat Population

A participant with premature rupture of membrane typically recalls a sudden gush of fluid loss from the vagina, or steady loss of small amounts of fluid. Participants who reported vaginal discharge were examined by a physician.

Outcome measures

Measure	Progesterone Cervical Pessary (6.3 g) n=91 Participants Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.	Progesterone Cervical Pessary (7.7 g) n=90 Participants Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.	Progesterone 200 mg Vaginal Capsules n=90 Participants Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Number of Participants With Premature Rupture of Membranes	1 Participants	4 Participants	3 Participants

SECONDARY outcome

Timeframe: Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.

Population: Intention-to-treat (ITT).

During the pregnancy the length of the uterine cervix will be assessed. The rational is that premature birth is associated with uterine cervix shortening. The length of the cervix was determined using ultrasound examination. A positive change from baseline indicates a positive development, i.e. less likely to result in a preterm birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed.

Outcome measures

Measure	Progesterone Cervical Pessary (6.3 g) n=91 Participants Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.	Progesterone Cervical Pessary (7.7 g) n=90 Participants Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.	Progesterone 200 mg Vaginal Capsules n=90 Participants Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Anatomical Feature: Length of the Uterine Cervix Final Visit	22.98 millimeter Standard Deviation 8.06	25.07 millimeter Standard Deviation 7.49	23.64 millimeter Standard Deviation 9.26
Anatomical Feature: Length of the Uterine Cervix Baseline Visit	28.69 millimeter Standard Deviation 9.06	29.62 millimeter Standard Deviation 8.66	28.44 millimeter Standard Deviation 8.55
Anatomical Feature: Length of the Uterine Cervix Visit 2	28.51 millimeter Standard Deviation 8.30	30.34 millimeter Standard Deviation 7.63	29.29 millimeter Standard Deviation 10.37
Anatomical Feature: Length of the Uterine Cervix Visit 3	27.54 millimeter Standard Deviation 7.27	29.06 millimeter Standard Deviation 7.65	30.76 millimeter Standard Deviation 8.28
Anatomical Feature: Length of the Uterine Cervix Visit 4	27.82 millimeter Standard Deviation 7.12	27.60 millimeter Standard Deviation 7.91	29.37 millimeter Standard Deviation 8.16
Anatomical Feature: Length of the Uterine Cervix Visit 5	27.53 millimeter Standard Deviation 7.40	26.55 millimeter Standard Deviation 7.81	28.63 millimeter Standard Deviation 10.16
Anatomical Feature: Length of the Uterine Cervix Visit 6	27.42 millimeter Standard Deviation 7.62	27.28 millimeter Standard Deviation 9.36	27.49 millimeter Standard Deviation 8.32
Anatomical Feature: Length of the Uterine Cervix Visit 7	30.43 millimeter Standard Deviation 9.39	27.95 millimeter Standard Deviation 8.85	28.83 millimeter Standard Deviation 8.00

SECONDARY outcome

Timeframe: Up to 36 weeks of gestational age. Results are reported for all assessments from baseline through final visit, for a total of 8 visits, and for up to 36 weeks of gestational age.

Population: Intention-to-treat (ITT).

During the pregnancy the position of the uterine cervix will be assessed. The rational being that premature birth is associated with uterine cervix positioning. The position of the cervix was determined using transvaginal ultrasound examination. In the change from baseline visit a positive value change indicated that the investigator believed that the position of the cervix changed in a positive manner to facilitate a term birth. The comparison between premature an normal birth initially planned by the protocol was not analyzed. The results reported are the degrees of the cervix position relative to the longitudinal axis of the uterus.

Outcome measures

Measure	Progesterone Cervical Pessary (6.3 g) n=91 Participants Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.	Progesterone Cervical Pessary (7.7 g) n=90 Participants Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.	Progesterone 200 mg Vaginal Capsules n=90 Participants Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Anatomical Feature: Position of the Uterine Cervix Baseline Visit	114.54 degrees Standard Deviation 22.58	112.59 degrees Standard Deviation 22.48	112.85 degrees Standard Deviation 20.03
Anatomical Feature: Position of the Uterine Cervix Visit 2	111.47 degrees Standard Deviation 23.33	115.02 degrees Standard Deviation 19.56	109.74 degrees Standard Deviation 23.56
Anatomical Feature: Position of the Uterine Cervix Visit 3	110.81 degrees Standard Deviation 17.78	109.83 degrees Standard Deviation 25.65	115.36 degrees Standard Deviation 24.93
Anatomical Feature: Position of the Uterine Cervix Visit 4	105.58 degrees Standard Deviation 21.35	117.61 degrees Standard Deviation 18.63	113.29 degrees Standard Deviation 26.20
Anatomical Feature: Position of the Uterine Cervix Visit 5	108.99 degrees Standard Deviation 21.97	115.50 degrees Standard Deviation 19.15	113.26 degrees Standard Deviation 15.21
Anatomical Feature: Position of the Uterine Cervix Visit 6	112.96 degrees Standard Deviation 17.41	114.50 degrees Standard Deviation 21.61	121.65 degrees Standard Deviation 15.89
Anatomical Feature: Position of the Uterine Cervix Visit 7	118.93 degrees Standard Deviation 14.10	110.51 degrees Standard Deviation 20.94	124.37 degrees Standard Deviation 13.32
Anatomical Feature: Position of the Uterine Cervix Final Visit	104.30 degrees Standard Deviation 23.98	113.42 degrees Standard Deviation 24.76	115.44 degrees Standard Deviation 16.14

SECONDARY outcome

Timeframe: Up to 36 weeks of gestational age

Population: No participants were analyzed

A questionnaire was planned to be used to compare acceptability and tolerance in the insertion, during pregnancy and during the extraction of Cerclage Pessary.

Data from this questionnaire was not collected.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 36 weeks of gestational age

Population: Intention-to-treat (ITT)

The number of adverse events reported were analyzed as being related with the treatment as well as for unexpectedness.

Outcome measures

Measure	Progesterone Cervical Pessary (6.3 g) n=200 number of adverse events Cervical Pessary with sustained release of progesterone.Single placement and removal by investigator site.	Progesterone Cervical Pessary (7.7 g) n=248 number of adverse events Cervical Pessary with sustained release of progesterone. Single placement and removal by investigator site.	Progesterone 200 mg Vaginal Capsules n=200 number of adverse events Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily by participant.
Number of Adverse Events Related With the Use of Treatment AE related to use of treatment	31 events	22 events	2 events
Number of Adverse Events Related With the Use of Treatment Unexpected serious adverse events	1 events	2 events	0 events

Adverse Events

Progesterone Cervical Pessary 6.3 g

Serious events: 36 serious events

Other events: 77 other events

Deaths: 0 deaths

Progesterone Cervical Pessary 7.7 g

Serious events: 35 serious events

Other events: 73 other events

Deaths: 0 deaths

Progesterone 200 mg Vaginal Capsules

Serious events: 33 serious events

Other events: 65 other events

Deaths: 0 deaths

Serious adverse events

Measure	Progesterone Cervical Pessary 6.3 g n=91 participants at risk 91 pregnant women with Progesterone Cervical Pessary Progesterone Cervical Pessary: Progesterone Cervical Pessary: 6.3 g Progesterone Cervical Pessary: 7.7 g	Progesterone Cervical Pessary 7.7 g n=90 participants at risk 90 pregnant women with Progesterone Cervical Pessary Progesterone Cervical Pessary: Progesterone Cervical Pessary: 6.3 g Progesterone Cervical Pessary: 7.7 g	Progesterone 200 mg Vaginal Capsules n=90 participants at risk 90 pregnant women using Progesterone 200 mg vaginal capsules daily Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily
Infections and infestations Breast abscess	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Cervical incompetence	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Foetal death	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Foetal growth restriction	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Vascular disorders Hypertensive crisis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Oligohydramnios	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Preeclampsia	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Premature rupture of membranes	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	4.4% 4/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Renal and urinary disorders Proteinuria	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Shortened cervix	11.0% 10/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	10.0% 9/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	21.1% 19/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Threatened labour	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Urinary tract infection	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Blood and lymphatic system disorders Anaemia	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Asymptomatic bacteriuria	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Bacterial vaginosis	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Nervous system disorders Cerebral ventricle dilatation	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Gestational hypertension	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Haemorrhage in pregnancy	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Pelvic pain	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Polihidroamnios	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Pyelonephritis acute	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Congenital, familial and genetic disorders Ventricular hypoplasia	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Psychiatric disorders Drug use disorder	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Metabolism and nutrition disorders Diabetic Metabolic Decompensation	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	4.4% 4/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Hepatobiliary disorders Cholelithiasis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Umbilical cord abnormality	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Renal and urinary disorders Hydronephrosis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Musculoskeletal and connective tissue disorders Pelvic pain	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Musculoskeletal and connective tissue disorders Pain in extremity	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Investigations Blood Pressure Increased	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Premature labor	18.7% 17/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	6.7% 6/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Renal and urinary disorders Renal Colic	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Hepatobiliary disorders Cholestasis	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Foetal hypokinesia	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Bacteriuria	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Nervous system disorders Foetal cerebrovascular disorder	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Vaginal erosion	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Congenital, familial and genetic disorders Multiple congenital anomalies	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
General disorders Pyrexia	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Vaginal infection NOS	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions HELLP syndrome	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Coital bleeding	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Cervix haemorrhage uterine	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Uterine contractions during pregnancy	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Uterine haemorrhage	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.

Other adverse events

Measure	Progesterone Cervical Pessary 6.3 g n=91 participants at risk 91 pregnant women with Progesterone Cervical Pessary Progesterone Cervical Pessary: Progesterone Cervical Pessary: 6.3 g Progesterone Cervical Pessary: 7.7 g	Progesterone Cervical Pessary 7.7 g n=90 participants at risk 90 pregnant women with Progesterone Cervical Pessary Progesterone Cervical Pessary: Progesterone Cervical Pessary: 6.3 g Progesterone Cervical Pessary: 7.7 g	Progesterone 200 mg Vaginal Capsules n=90 participants at risk 90 pregnant women using Progesterone 200 mg vaginal capsules daily Progesterone 200 mg vaginal capsules: Progesterone 200 mg vaginal capsules daily
Blood and lymphatic system disorders Anaemia	12.1% 11/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	5.6% 5/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	5.6% 5/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Cardiac disorders Sinus tachycardia	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Congenital, familial and genetic disorders Congenital uterine anomaly	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Ear and labyrinth disorders Vertigo	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Endocrine disorders Hypothyroidism	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	4.4% 4/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Abdominal pain	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Abdominal pain lower	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Constipation	5.5% 5/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	4.4% 4/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Dental caries	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Diarrhoea	5.5% 5/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Dyspepsia	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Flatulence	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Gastritis	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Gastrooesophageal reflux disease	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Haemorrhoids	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Hyperchlorhydria	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Nausea	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Vomiting	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	7.8% 7/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Faecaloma	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Gastrointestinal disorders Duodenogastric reflux	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
General disorders Oedema peripheral	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Hepatobiliary disorders Cholelithiasis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Hepatobiliary disorders Cholestasis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Immune system disorders Hypersensitivity	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Bacterial vaginosis	15.4% 14/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	5.6% 5/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Bronchitis	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Cervicitis	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Fungal infection	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Gastrenteritis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Herpes zoster	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Influenza	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Pharyngitis	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Pneumonia	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Sinusitis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Tonsillitis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Urinary tract infection	13.2% 12/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	12.2% 11/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	6.7% 6/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Vaginal infection	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Vaginitis gardnerella	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Viral pharyngitis	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Viral upper respiratory tract infection	12.1% 11/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	7.8% 7/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	8.9% 8/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Vulvovaginal candidasis	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	4.4% 4/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Vulvovaginitis	14.3% 13/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	6.7% 6/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	12.2% 11/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Tooth infection	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Gynaecological chlamydia infection	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Ureaplasma infection	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Mycoplasma infection	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Vulvovaginal mycotic infection	17.6% 16/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	12.2% 11/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	11.1% 10/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Infections and infestations Vaginitis chlamydial	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Injury, poisoning and procedural complications Arthropod bite	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Injury, poisoning and procedural complications Fall	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Injury, poisoning and procedural complications Thermal burn	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Injury, poisoning and procedural complications Tooth fracture	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Investigations Amniocentesis abnormal	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Investigations Ultrasound uterus	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Investigations Ultrasound uterus abnormal	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Investigations Ureaplasma test positive	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Investigations Mycoplasma test positive	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Investigations Foetal renal imaging abnormal	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Metabolism and nutrition disorders Diabetic metabolic decompensation	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Musculoskeletal and connective tissue disorders Arthralgia	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Musculoskeletal and connective tissue disorders Back pain	4.4% 4/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	6.7% 6/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Musculoskeletal and connective tissue disorders Coccydynia	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Musculoskeletal and connective tissue disorders Myalgia	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Musculoskeletal and connective tissue disorders Pubic pain	5.5% 5/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	6.7% 6/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Vulvovaginal warts	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Nervous system disorders Carpal tunnel syndrome	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Nervous system disorders Dizziness	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Nervous system disorders Facial paralysis	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Nervous system disorders Headache	8.8% 8/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	13.3% 12/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Nervous system disorders Tension headache	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Gestational diabetes	6.6% 6/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	12.2% 11/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	7.8% 7/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Haemorrhage in pregnancy	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Polyhydramnios	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	4.4% 4/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Premature labour	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Premature rupture of membranes	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Threatened labour	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Uterine hypotonus	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Umbilical cord abnormaility	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Uterine contractions during pregnancy	12.1% 11/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	13.3% 12/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	10.0% 9/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Uterine contractions abnormal	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Foetal hypokinesia	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Gestational hypertension	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Pregnancy, puerperium and perinatal conditions Uterine irritability	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Psychiatric disorders Insomnia	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Renal and urinary disorders Dysuria	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Renal and urinary disorders Pollakiuria	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Renal and urinary disorders Urinary incontinence	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Renal and urinary disorders Bladder spasm	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Ovarian cyst	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Pelvic pain	13.2% 12/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	6.7% 6/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	12.2% 11/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Pruritus genital	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Uterine haemorrhage	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Vaginal discharge	17.6% 16/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	24.4% 22/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Vaginal haemorrhage	3.3% 3/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Vuvovaginal pruritus	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Cervix haemorrhage uterine	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Vulvovaginal discomfort	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Genital discharge	4.4% 4/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Vaginal erosion	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Cervix oedena	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Shortened cervix	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	2.2% 2/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Reproductive system and breast disorders Vulvovaginal pain	2.2% 2/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	4.4% 4/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Respiratory, thoracic and mediastinal disorders Bronchospasm	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Respiratory, thoracic and mediastinal disorders Productive cough	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Skin and subcutaneous tissue disorders Dermatitis atopic	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Skin and subcutaneous tissue disorders Pruritus	1.1% 1/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	3.3% 3/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Skin and subcutaneous tissue disorders Skin striae	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Skin and subcutaneous tissue disorders Utricaria	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	0.00% 0/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.
Skin and subcutaneous tissue disorders Pruritus allergic	0.00% 0/91 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.	1.1% 1/90 • up to 36 weeks of gestational age (participants were in the trial for up to 20 weeks). Treatment emergent adverse events.

Additional Information

Director of Clinical Trials

Grünenthal GmbH

Phone: +49 241 569 3223

Email: clinical-trials@grunenthal.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: OTHER