An Open-label Trial Investigating the Efficacy and Safety of a Vaginal Insert in Pregnant Women at Term

A Multicentre, Open-label Phase III Trial Investigating the Efficacy and Safety of FE 999901 Vaginal Insert in Pregnant Women at Term (≥37 Weeks and <41 Weeks of Gestation) Requiring Cervical Ripening

To demonstrate the efficacy of controlled-release 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 (≥37 weeks 0 day and < 41 weeks 0 day 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 active 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 (≤ mean 1.5 SD of 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 V2
• Ruptured membranes ≥ 48 hours prior to IMP administration
• 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 (e.g., 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 investigators would impair participation in the trial