Misoprostol Vaginal Insert (MVI) 100, 150, 200 mcg for Cervical Ripening and Induction of Labor

A Multicenter, Randomized, Double-Blind, Dose-Ranging, Phase II Study to Assess the Efficacy and Safety of the 100, 150 and 200 mcg Misoprostol Vaginal Insert for Women Requiring Cervical Ripening and Induction of Labor

The purpose of this study is to assess the efficacy and safety of the 100, 150 and 200 mcg Misoprostol Vaginal Insert (MVI 100, MVI 150 and MVI 200) for women requiring cervical ripening and induction of labor.

Study Overview

• Status: Completed
• Conditions: Induction of Labor; Cervical Ripening
• Intervention / Treatment: Drug: MVI 200; Drug: MVI 100; Drug: MVI 150

• Study Type: Interventional
• Enrollment (Actual): 374
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Precision Trials
    • Tucson, Arizona, United States, 85716
      • Tuscon Medical Center
  • California
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Orange, California, United States, 92868
      • UCI Medical Center
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico Medical Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27103
      • Forsyth Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple University Hospital
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Greenville Hospital System
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennesse Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Sciences Center at Houston

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Provide written informed consent;
• Pregnant women at ≥ 36 weeks 0 days inclusive gestation;
• Women aged 18 years or older;
• Candidate for pharmacologic induction of labor;
• Single, live vertex fetus;
• Baseline modified Bishop score ≤ 4;
• Parity ≤ 3 (parity is defined as one or more births live or dead after 24 weeks gestation);
• Body Mass Index (BMI) ≤ 50 at the time of entry to the study.

Exclusion Criteria:

• Nulliparous women participating in the pharmacokinetic (PK) arm of the study: women with hemoglobin level < 11.0 grams per deciliter (g/dL) (confirmed within one week of study drug insertion);
• Women in active labor;
• Presence of uterine or cervical scar or uterine abnormality e.g., bicornate uterus. Biopsies, including cone biopsy of the cervix, are permitted;
• Administration of oxytocin or any cervical ripening or labor inducing agents (including mechanical methods) or a tocolytic drug within 7 days prior to enrollment. Magnesium sulfate is permitted if prescribed as treatment for pre-eclampsia or gestational hypertension;
• Severe pre-eclampsia marked by Hemolytic anemia, Elevated Liver enzymes, Low Platelet count (HELLP) syndrome, other end-organ affliction or Central Nervous System (CNS) findings other than mild headache;
• Fetal malpresentation;
• Diagnosed fetal abnormalities;
• Any evidence of fetal compromise at baseline (e.g., non-reassuring fetal heart rate pattern or meconium staining);
• Ruptured membranes ≥ 48 hours prior to the start of treatment;
• Suspected chorioamnionitis;
• Fever (oral or aural temperature > 37.5˚C);
• Any condition in which vaginal delivery is contraindicated e.g., placenta previa or any unexplained genital bleeding at any time after 24 weeks during this pregnancy;
• Known or suspected allergy to misoprostol, other prostaglandins or any of the excipients;
• Any condition urgently requiring delivery;
• Unable to comply with the protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: MVI 100; MVI 100 mcg vaginal insert	Drug: MVI 100; Dose reservoir of 100 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 100 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.; Other Names: Misopess (TM); Misodel (R)
EXPERIMENTAL: MVI 150; MVI 150 mcg vaginal insert	Drug: MVI 150; Dose reservoir of 150 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 150 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.; Other Names: Misopess (TM); Misodel (R)
EXPERIMENTAL: MVI 200; MVI 200 mcg vaginal insert	Drug: MVI 200; Dose reservoir of 200 mcg of misoprostol in a hydrogel polymer vaginal insert within a retrieval system. The MVI 200 will be kept in place for up to 24 hours or will be removed earlier if one of the following occur: onset of active labor, intrapartum adverse event necessitating discontinuation of the study drug, other reasons including maternal request.; Other Names: Misopess (TM); Misodel (R)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of Women Delivering Vaginally	Interval from study drug administration to 24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Vaginal Delivery		Interval from study drug administration to delivery (average 24 hours)
Rate of Adverse Events	All adverse events were rated by the Investigator as mild, moderate or severe and classified as having no relationship, possible relationship or a probable relationship to the study drug. These assessments were deemed as accurate and appropriate for the reporting of all serious and non serious adverse events.	From study drug administration to hospital discharge (approximately 48 - 72 hours)
Proportion of Cesarean Delivery		Interval from study drug administration to cesarean delivery (average 24 hours)
Cervical Ripening Using Composite Measure of Success	Cervical ripening success was defined by achievement of one or more of the following by 12 hours after study drug administration: Increase from baseline in modified Bishop score ≥3; or; Achievement of modified Bishop score of ≥6; or; Vaginal delivery.	12 hours after insertion of drug
Use of Oxytocin	Percentage of participants in receipt of Oxytocin for induction after study drug removal is accurate and appropriate for this outcome measure.	At least 30 minutes after study drug removal
Time of Maximum Plasma Concentration (Tmax), Maximum Plasma Concentration (Cmax), Area Under the Curve (AUC) and Terminal Half Life of Misoprostol Acid.	The timepoints over which the pharmacokinetic measurements were assessed, and deemed as accurate and appropriate, were as follows: 0 hours (baseline), 2, 4, 6, 8, 10 and 14 hours after insertion of the study drug, immediately prior to removal of the study drug and 0.5, 1 and 2 hours after removal of the study drug.	From study drug insertion up to 2 hours post study drug removal
Time to Onset of Active Labor		Interval from study drug administration to active labor (average 12 hours)

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals

Publications and helpful links

General Publications

• Wing DA, Miller H, Parker L, Powers BL, Rayburn WF; Misoprostol Vaginal Insert Miso-Obs-204 Investigators. Misoprostol vaginal insert for successful labor induction: a randomized controlled trial. Obstet Gynecol. 2011 Mar;117(3):533-541. doi: 10.1097/AOG.0b013e318209d669.

Study record dates

Study Major Dates

• Study Start: April 1, 2009
• Primary Completion (ACTUAL): December 1, 2009
• Study Completion (ACTUAL): December 1, 2009

Study Registration Dates

• First Submitted: January 22, 2009
• First Submitted That Met QC Criteria: January 23, 2009
• First Posted (ESTIMATE): January 26, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): April 21, 2014
• Last Update Submitted That Met QC Criteria: March 10, 2014
• Last Verified: March 1, 2014

More Information

Terms related to this study

• Keywords: Induction of labor; Cervical ripening; Misoprostol vaginal insert; Rate of cesarean section
• Other Study ID Numbers: Miso-Obs-204