Trial Outcomes & Findings for Confirmatory Study of 17P vs Vehicle for Prevention of Preterm Birth in Women w/ Previous Spontaneous Preterm Delivery (NCT NCT01004029)

Last Updated: 2022-06-01

Results Overview

Determine if treatment with 17P reduces the rate of preterm birth \< 35 weeks, 0 days of gestation in women with a previous singleton spontaneous preterm delivery.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1740 participants

Primary outcome timeframe

Up to 35 weeks

Results posted on

2022-06-01

Participant Flow

1740 subjects enrolled (signed the informed consent form), but only 1708 were randomized to each group (10 subjects did not return for Visit 2, 8 subjects did not meet all eligibility requirements, 8 subjects withdrew consent, and 6 subjects discontinued for other reasons).

Participant milestones

Participant milestones
Measure	Vehicle Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Overall Study STARTED	578	1130
Overall Study Safety Population	578	1128
Overall Study COMPLETED	530	1057
Overall Study NOT COMPLETED	48	73

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

One participant did not have height recorded therefore BMI could not be calculated.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vehicle n=578 Participants Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1130 Participants HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	Total n=1708 Participants Total of all reporting groups
Age, Continuous	29.9 years STANDARD_DEVIATION 5.22 • n=578 Participants	30 years STANDARD_DEVIATION 5.17 • n=1130 Participants	30.0 years STANDARD_DEVIATION 5.20 • n=1708 Participants
Sex: Female, Male Female	578 Participants n=578 Participants	1130 Participants n=1130 Participants	1708 Participants n=1708 Participants
Sex: Female, Male Male	0 Participants n=578 Participants	0 Participants n=1130 Participants	0 Participants n=1708 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	54 Participants n=578 Participants	101 Participants n=1130 Participants	155 Participants n=1708 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	524 Participants n=578 Participants	1029 Participants n=1130 Participants	1553 Participants n=1708 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=578 Participants	0 Participants n=1130 Participants	0 Participants n=1708 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=578 Participants	3 Participants n=1130 Participants	3 Participants n=1708 Participants
Race (NIH/OMB) Asian	22 Participants n=578 Participants	23 Participants n=1130 Participants	45 Participants n=1708 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=578 Participants	1 Participants n=1130 Participants	1 Participants n=1708 Participants
Race (NIH/OMB) Black or African American	41 Participants n=578 Participants	73 Participants n=1130 Participants	114 Participants n=1708 Participants
Race (NIH/OMB) White	504 Participants n=578 Participants	1004 Participants n=1130 Participants	1508 Participants n=1708 Participants
Race (NIH/OMB) More than one race	7 Participants n=578 Participants	8 Participants n=1130 Participants	15 Participants n=1708 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=578 Participants	18 Participants n=1130 Participants	22 Participants n=1708 Participants
Pre-pregnancy BMI (kg/m2), n	24.7 kg/m^2 STANDARD_DEVIATION 8.65 • n=577 Participants • One participant did not have height recorded therefore BMI could not be calculated.	24.3 kg/m^2 STANDARD_DEVIATION 7.05 • n=1130 Participants • One participant did not have height recorded therefore BMI could not be calculated.	24.5 kg/m^2 STANDARD_DEVIATION 7.62 • n=1707 Participants • One participant did not have height recorded therefore BMI could not be calculated.

PRIMARY outcome

Timeframe: Up to 35 weeks

Population: Number of ITT (intent to treat) subjects with non-missing delivery data or who were known to still be pregnant at 35 weeks

Determine if treatment with 17P reduces the rate of preterm birth \< 35 weeks, 0 days of gestation in women with a previous singleton spontaneous preterm delivery.

Outcome measures

Outcome measures
Measure	Vehicle n=574 Participants Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1113 Participants HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Preterm Birth <35 Weeks Gestation	66 Participants	122 Participants

PRIMARY outcome

Timeframe: Until 28 days of life or discharge from the neonatal intensive care unit (NICU), whichever occurred later.

Population: Liveborn Neonatal Population

The composite index is defined as a liveborn neonate with any of the following occurring at any time during the birth hospitalization up through discharge from the NICU: neonatal death, grade 3 or 4 intraventricular hemorrhage, respiratory distress syndrome, bronchopulmonary dysplasia, necrotizing enterocolitis or proven sepsis.

Outcome measures

Outcome measures
Measure	Vehicle n=559 Participants Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1093 Participants HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Neonatal Composite Index (NCI)	28 Participants	61 Participants

SECONDARY outcome

Timeframe: Delivery from 16 weeks 0 days through 19 weeks 6 days of gestation; or neonatal death occurring in liveborns born at less than 24 weeks gestation; or stillbirth (antepartum or intrapartum death) from 20 weeks gestation through term).

Population: Intent to Treat (ITT) Population - all randomized subjects regardless of whether they received study medication.

Defined as spontaneous abortion/miscarriage (delivery from 16 weeks 0 days through 19 weeks 6 days of gestation) or neonatal death occurring in liveborns born at less than 24 weeks gestation or stillbirth (antepartum or intrapartum death from 20 weeks gestation through term), in the 17P group compared to the vehicle group

Outcome measures

Outcome measures
Measure	Vehicle n=578 Participants Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1130 Participants HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Fetal/Early Infant Death	11 Participants	19 Participants

SECONDARY outcome

Timeframe: Up to 32 weeks

Population: Intent to Treat (ITT) Population - all randomized subjects regardless of whether they received study medication.

Outcome measures

Outcome measures
Measure	Vehicle n=578 Participants Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1130 Participants HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Preterm Birth Prior to 32 Weeks Gestation	30 Participants	54 Participants

SECONDARY outcome

Timeframe: Up to 37 weeks

Population: Intent to Treat (ITT) Population - all randomized subjects regardless of whether they received study medication.

Outcome measures

Outcome measures
Measure	Vehicle n=578 Participants Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1130 Participants HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Preterm Birth Prior to 37 Weeks Gestation	125 Participants	257 Participants

SECONDARY outcome

Timeframe: 20 weeks gestation until term

Defined as all stillbirths/fetal deaths/in utero fetal losses occurring from 20 weeks gestation until term.

Outcome measures

Outcome measures
Measure	Vehicle n=559 Participants Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1093 Participants HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Stillbirths	3 Participants	12 Participants

SECONDARY outcome

Timeframe: Until 28 days of life or discharge from the NICU whichever occurred later.

Population: Liveborn Neonatal Population - all babies of randomized women who were liveborn and have morbidity data available.

Neonatal death (from minutes after birth until 28 days of life) occurring in liveborns born at 24 weeks gestation or greater

Outcome measures

Outcome measures
Measure	Vehicle n=558 Participants Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1093 Participants HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Neonatal Deaths With ≥24 Weeks Gestational Age	2 Participants	3 Participants

Adverse Events

Vehicle

Serious events: 18 serious events

Other events: 334 other events

Deaths: 0 deaths

17P (Hydroxyprogesterone Caproate Injection)

Serious events: 34 serious events

Other events: 647 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Clinical Trial Interest

Covis Pharma

Phone: 1-877-374-4177

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	Vehicle n=578 participants at risk Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1128 participants at risk HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Hepatobiliary disorders Cholestasis	0.52% 3/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Reproductive system and breast disorders Endometritis	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Escherichia sepsis	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.18% 2/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Nervous system disorders Migraine	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Pregnancy, puerperium and perinatal conditions Placental insufficiency	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.35% 4/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Pneumonia	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.27% 3/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Pregnancy, puerperium and perinatal conditions Premature separation of placenta	0.35% 2/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.44% 5/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Renal and urinary disorders Pyelonephritis	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.18% 2/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Wound infection	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.18% 2/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Blood and lymphatic system disorders Anaemia	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Blood and lymphatic system disorders Iron deficiency anaemia	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Constipation	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Pancreatitis relapsing	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
General disorders Chest pain	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
General disorders Oedema peripheral	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
General disorders Pyrexia	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Hepatobiliary disorders Cholestasis of pregnancy	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Amniotic cavity infection	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Choriaoamnionitis	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Clostridial infection	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Endometritis	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Endometritis decidual	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Kidney infection	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Mastitis postpartum	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Pelvic abcess	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Postoperative wound infection	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Urinary tract infection	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Injury, poisoning and procedural complications abdominal wound dehiscence	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Injury, poisoning and procedural complications bladder injury	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Incision site haematoma	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Injury, poisoning and procedural complications Incision site haemorrhage	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Injury, poisoning and procedural complications Post-traumatic pain	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Investigations Biopsy chorionic villous abnormal	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Metabolism and nutrition disorders Dehydration	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Metabolism and nutrition disorders Hyperglycaemia	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Nervous system disorders Central nervous system inflammation	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Pregnancy, puerperium and perinatal conditions Antepartum haemorrhage	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Pregnancy, puerperium and perinatal conditions Pre-eclampsia	0.17% 1/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.00% 0/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Psychiatric disorders Confusion state	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Renal and urinary disorders Hydronephrosis	0.00% 0/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	0.09% 1/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.

Other adverse events
Measure	Vehicle n=578 participants at risk Castor Oil Vehicle: Weekly intramuscular injections of 1 mL vehicle inert oil until 36 weeks, 6 days of gestation or delivery, whichever occurs first.	17P (Hydroxyprogesterone Caproate Injection) n=1128 participants at risk HPC 250 mg/mL in oil Hydroxyprogesterone Caproate Injection, 250mg/mL: 1 mL intramuscular injection every week until 36 weeks, 6 days of gestation or delivery, whichever occurs first.
Blood and lymphatic system disorders Anaemia	9.7% 56/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	9.2% 104/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Blood and lymphatic system disorders Anaemia of pregnancy	3.1% 18/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	2.7% 30/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Abdominal pain	4.7% 27/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.5% 40/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Abdominal pain lower	1.2% 7/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	2.0% 23/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Constipation	2.9% 17/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.4% 38/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Diarrhoea	2.2% 13/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	2.0% 23/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Dyspepsia	4.3% 25/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.3% 37/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Nausea	4.5% 26/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	4.9% 55/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Gastrointestinal disorders Vomiting	3.3% 19/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.7% 42/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
General disorders Injection site pain	4.2% 24/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.2% 36/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
General disorders Injection site pruritus	4.0% 23/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.7% 42/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
General disorders Oedema peripheral	1.9% 11/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	2.2% 25/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Nasopharyngitis	4.7% 27/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.5% 39/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Urinary tract infection	4.0% 23/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.9% 44/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Vaginal infection	3.6% 21/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.6% 41/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Vaginitis bacterial	3.8% 22/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.1% 35/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Infections and infestations Vulvovaginal candidiasis	2.1% 12/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	1.9% 21/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Metabolism and nutrition disorders Gestational diabetes	3.6% 21/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	2.9% 33/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Musculoskeletal and connective tissue disorders Back pain	3.5% 20/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	4.4% 50/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Nervous system disorders Dizziness	2.2% 13/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	2.0% 22/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Nervous system disorders Headache	4.8% 28/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	6.0% 68/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Pregnancy, puerperium and perinatal conditions Afterbirth pain	4.2% 24/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	4.3% 48/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Pregnancy, puerperium and perinatal conditions Cervical incompetence	2.8% 16/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.0% 34/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Pregnancy, puerperium and perinatal conditions Placental disorder	1.9% 11/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	2.5% 28/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Psychiatric disorders Insomnia	2.2% 13/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	3.2% 36/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Reproductive system and breast disorders Shortened cervix	2.6% 15/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	1.6% 18/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Skin and subcutaneous tissue disorders Pruritus	2.2% 13/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	1.5% 17/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.
Pregnancy, puerperium and perinatal conditions Preeclampsia	3.8% 22/578 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.	2.6% 29/1128 • Randomized subjects were followed up to 35 ± 7 days after the last dose of study drug. Maternal and fetal deaths were reported until delivery if delivery occurred after 35 ± 7 days after last dose. Subjects reporting a particular adverse event (preferred term) or maternal pregnancy complication more than once are counted only once by preferred term and System Organ Class. All cause mortality used the ITT population. Serious and Other Adverse events used the Safety population.