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

• ClinicalTrials.gov Identifier: NCT03067597
• Recruitment Status: Completed
• First Posted: March 1, 2017
• Last Update Posted: April 9, 2021
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cervical Ripening	Drug: Dinoprostone	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 68 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: February 22, 2017
• Actual Primary Completion Date: February 24, 2018
• Actual Study Completion Date: February 24, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: Dinoprostone vaginal insert (DVI)	Drug: Dinoprostone; The DVI contains 10 mg dinoprostone; Other Names: CERVIDIL®; PROPESS®

Outcome Measures

Primary Outcome Measures :

1. The proportion of women with cervical ripening success [ Time Frame: Within 12 hours of vaginal insert administration ]
   Defined as either Bishop Score (BS) ≥7 or a vaginal delivery

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

Japan

Yokota Maternity Hospital

Maebashi, Gunma, Japan

Kitasato University Hospital

Sagamihara, Kanagawa, Japan

Osaka Medical Center and Research Institute for Maternal and Child Health

Izumi, Osaka, Japan

Hamamatsu University Hospital

Hamamatsu, Shizuoka, Japan

Seirei Hamamatsu General Hospital

Hamamatsu, Shizuoka, Japan

Jichi Medical University Hospital

Shimotsuke, Tochigi, Japan

Itabashi Chuo Medical Center

Itabashi, Tokyo, Japan

University of Tsukuba Hospital

Ibaraki, Tsukuba, Japan

Hori Hospital

Kanagawa, Japan

Rinku General Medical Center

Osaka, Japan

Juntendo University Hospital

Tokyo, Japan

Keio University Hospital

Tokyo, Japan

The University of Tokyo Hospital

Tokyo, Japan

Tokyo Metropolitan Bokutoh Hospital

Tokyo, Japan

Sponsors and Collaborators

Ferring Pharmaceuticals

Investigators

• Study Director: Clinical Development Support; Ferring Pharmaceuticals

More Information

Additional Information:

Related Info 

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03067597
• Other Study ID Numbers: 000261
• First Posted: March 1, 2017
• Last Update Posted: April 9, 2021
• Last Verified: March 2018

• 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

Additional relevant MeSH terms:

Dinoprostone; Oxytocics; Reproductive Control Agents; Physiological Effects of Drugs