A Randomised Trial Investigating the Efficacy and Safety of a Vaginal Insert in Pregnant Women at Term

Study Overview
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Brief Summary
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To demonstrate the efficacy of dinoprostone vaginal insert (DVI) for cervical ripening success (either bishop score (BS) ≥7 or vaginal delivery) within 12 hours of vaginal insert administration

Official Title
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A Multicentre, Randomised, Double-blind, Placebo-controlled Phase III Trial Investigating the Efficacy and Safety of FE 999901 Vaginal Insert in Pregnant Women at Term (41 Weeks of Gestation) Requiring Cervical Ripening

Conditions
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Cervical Ripening

Intervention / Treatment
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* Drug: Dinoprostone
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pregnant women at term (≥ 41 weeks 0 day and ≤ 41 weeks 6 days of gestation) at the Baseline visit Candidate for pharmacologic induction of labour Singleton pregnancy with live infant in vertex presentation Baseline BS ≤ 4 at the Baseline visit Parity ≤ 3 (parity is defined as one or more births live or stillbirths after 22 weeks 0 day gestation) Written informed consent Exclusion Criteria: Women in labour Presence of uterine or cervical scar including scar from previous caesarean section, and previous cone biopsy of the cervix and loop electrosurgical excision procedure (LEEP) Uterine abnormality e.g. bicornuate uterus Administration of oxytocin, any cervical ripening or labour inducing agents (including mechanical methods) or a tocolytic drug within 7 days prior to IMP administration. Magnesium sulfate is permitted if prescribed as treatment for preeclampsia or pregnancy induced hypertension Presence of the following conditions/symptoms: Systolic blood pressure > 160 mmHg or diastolic blood pressure > 110 mmHg. Platelets < 100,000/µL. Increased liver function tests (2x upper limits of normal range). Severe, persistent right upper quadrant/epigastric pain. Progressive renal insufficiency: Creatinine > 1.1 mg/dL, Doubling of creatinine in the absence of other renal disease. Pulmonary edema. New onset cerebral or visual disturbances Suspected or confirmed cephalopelvic disproportion and/or fetal malpresentation Diagnosed congenital abnormalities, not including polydactyly Suspected or confirmed intrauterine growth retardation (≤ 1.5 SD of mean normal estimated fetal weight for dates) Any evidence of fetal compromise at baseline visit (e.g., non-reassuring fetal heart rate pattern, meconium staining, history of non-reassuring fetal status or abnormal umbilical artery Doppler wave form) Intake of medication with aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) at baseline visit Ruptured membranes Suspected clinical chorioamnionitis Current pelvic inflammatory disease, unless adequate prior treatment has been instituted Fever (axillary temperature ≥ 38.0 °C) at the Baseline visit Any condition in which vaginal delivery is contraindicated (eg., placenta previa or any unexplained vaginal bleeding at any time after 24 weeks 0 day during this pregnancy) Known or suspected allergy to, dinoprostone other prostaglandins or any constituent of IMP Any condition urgently requiring delivery History of asthma or glaucoma Unable to comply with the protocol Any other medical condition which in the judgement of the investigator would impair participation in the trial

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dinoprostone vaginal insert<br> | Drug: Dinoprostone<br>* The DVI contains 10 mg Dinoprostone<br>* Other names: PROPESS®;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* The placebo product is identical with the active product except that it does not contain Dinoprostone.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of women with cervical ripening success | Defined as either Bishop Score (BS) ≥7 or a vaginal delivery | Within 12 hours of vaginal insert administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of nulliparous and multiparous subjects with cervical ripening success | Collected labour data and delivery data | Within 12 hours of Investigational Medicinal Product (IMP) administration | 
| Proportion of subjects delivering vaginally | Collected labour and delivery data | Within 12 hours of IMP administration | 
| Proportion of subjects delivering vaginally | Collected labour data and delivery data | Within the first admission to hospital | 
| Proportion of subjects with a BS increase ≥3 points from baseline | Measured by BS assessments | Within 12 hours of IMP administration | 
| Proportion of subjects who have a caesarean delivery within the first admission to hospital | Data collected during the first admission to hospital | At time of delivery | 
| Proportion of subjects who receive pre-delivery oxytocic drugs and dose of pre-delivery oxytocic drugs | Collected pre-delivery data | From the IMP removal to delivery | 
| Proportion of subjects who undergo mechanical cervical ripening | Collected labour data | At least 60 minutes after the removal of the IMP | 
| Duration of mechanical cervical ripening for subjects who undergo mechanical Cervical ripening | Measured as start date and time of first mechanical ripening and the end date and time of last mechanical ripening | Time from at least 60 minutes after the removal of the IMP until end of any mechanical ripening | 
| Proportion of subjects with BS ≥7 | Among those having onset of labour while IMP is in-situ | At onset of labour | 
| Time from IMP administration to onset of active labour | Within the first admission to hospital | Interval from IMP administration to onset of active labour | 
| Time from IMP administration to vaginal delivery, caesarean delivery and any delivery | Within the first admission to hospital | Interval from IMP administration to delivery | 
| Type, frequency and intensity of intrapartum adverse events (AEs), postpartum AEs and neonatal AEs | Assessed up to time when the subjects are discharged from the hospital | From obtaining the informed consent through end of trial (expected average of up to 1 week) | 
| Type, frequency and intensity of intrapartum AEs | Assessed up to time when the deliveries occur | From onset of labour to the removal of the IMP | 
| Change in maternal parameters of vital signs (blood pressure, heart rate and body temperature) | Assessed up to time when the subjects are discharged from the hospital | From baseline through end of trial (expected average of up to 1 week) | 
| Change in maternal parameters of haematology, clinical chemistry and urinalysis | Assessed up to time when the subjects are discharged from the hospital | From baseline to end of trial (expected average of up to 1 week) | 
| Proportion of neonates with Apgar Score <7 | Measured as Apgar Score assessments | 5 minutes post-birth | 
| pH in umbilical artery blood samples | pH evaluation | At birth | 
| Rate of admission to neonatal intensive care unit (NICU) for at least 24 hours | Admission/discharge data from NICU | After delivery |