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

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

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

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