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

Study Overview

• Status: Completed
• Conditions: Cervical Ripening
• Intervention / Treatment: Drug: Dinoprostone; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 114
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Chiba, Japan
    • Asahi General Hospital
  • Ibaraki, Japan
    • University of Tsukuba Hospital
  • Kanagawa, Japan
    • Hori Hospital
  • Osaka, Japan
    • Aizenbashi Hospital
  • Osaka, Japan
    • Osaka University Hospital
  • Osaka, Japan
    • Rinku General Medical Center
  • Tokyo, Japan
    • Keio University Hospital
  • Tokyo, Japan
    • Juntendo University Hospital
  • Tokyo, Japan
    • Seibo Hospital
  • Tokyo, Japan
    • Showa University Hospital
  • Tokyo, Japan
    • St.Luke's International Hospital
  • Tokyo, Japan
    • The University of Tokyo Hospital
  • Tokyo, Japan
    • Tokyo Metropolitan Bokutoh Hospital
  • Tokyo, Japan
    • Tokyo Metropolitan Tama Medical Center
  • Yokohama, Japan
    • Keiyu Hospital
  • Osaka
    • Izumi, Osaka, Japan
      • Osaka Medical Center and Research Institute for Maternal and Child Health
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan
      • Hamamatsu University Hospital
    • Hamamatsu, Shizuoka, Japan
      • Seirei Hamamatsu General Hospital
  • Tochigi
    • Shimotsuke, Tochigi, Japan
      • Jichi Medical University Hospital
  • Tokyo
    • Itabashi, Tokyo, Japan
      • Itabashi Chuo Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Publications and helpful links

General Publications

• Itoh H, Ishii K, Shigeta N, Itakura A, Hamada H, Nagamatsu T, Ishida T, Bungyoku Y, Falahati A, Tomisaka M, Kitamura M. Efficacy and safety of controlled-release dinoprostone vaginal delivery system (PROPESS) in Japanese pregnant women requiring cervical ripening: Results from a multicenter, randomized, double-blind, placebo-controlled phase III study. J Obstet Gynaecol Res. 2021 Jan;47(1):216-225. doi: 10.1111/jog.14472. Epub 2020 Oct 22.

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2017
• Primary Completion (Actual): August 30, 2018
• Study Completion (Actual): August 30, 2018

Study Registration Dates

• First Submitted: February 9, 2017
• First Submitted That Met QC Criteria: February 23, 2017
• First Posted (Actual): March 1, 2017

Study Record Updates

• Last Update Posted (Actual): November 3, 2020
• Last Update Submitted That Met QC Criteria: October 30, 2020
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Reproductive Control Agents; Oxytocics; Dinoprostone
• Other Study ID Numbers: 000262

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No