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

• ClinicalTrials.gov Identifier: NCT00828711
• Recruitment Status: Completed
• First Posted: January 26, 2009
• Results First Posted: April 21, 2014
• Last Update Posted: April 21, 2014
• Sponsor: Ferring Pharmaceuticals
• Information provided by (Responsible Party): Ferring Pharmaceuticals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Cervical Ripening; Induction of Labor	Drug: MVI 100; Drug: MVI 150; Drug: MVI 200	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 374 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: April 2009
• Actual Primary Completion Date: December 2009
• Actual Study Completion Date: December 2009

Arms and Interventions

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)

Outcome Measures

Primary Outcome Measures :

1. Proportion of Women Delivering Vaginally [ Time Frame: Interval from study drug administration to 24 hours ]

Secondary Outcome Measures :

1. Time to Vaginal Delivery [ Time Frame: Interval from study drug administration to delivery (average 24 hours) ]
2. Rate of Adverse Events [ Time Frame: From study drug administration to hospital discharge (approximately 48 - 72 hours) ]
   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.
3. Proportion of Cesarean Delivery [ Time Frame: Interval from study drug administration to cesarean delivery (average 24 hours) ]
4. Cervical Ripening Using Composite Measure of Success [ Time Frame: 12 hours after insertion of drug ]

   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.
5. Use of Oxytocin [ Time Frame: At least 30 minutes after study drug removal ]
   Percentage of participants in receipt of Oxytocin for induction after study drug removal is accurate and appropriate for this outcome measure.
6. Time of Maximum Plasma Concentration (Tmax), Maximum Plasma Concentration (Cmax), Area Under the Curve (AUC) and Terminal Half Life of Misoprostol Acid. [ Time Frame: From study drug insertion up to 2 hours post study drug removal ]
   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.
7. Time to Onset of Active Labor [ Time Frame: Interval from study drug administration to active labor (average 12 hours) ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, Arizona

Precision Trials

Phoenix, Arizona, United States, 85032

Tuscon Medical Center

Tucson, Arizona, United States, 85716

United States, California

Long Beach Memorial Medical Center

Long Beach, California, United States, 90806

UCI Medical Center

Orange, California, United States, 92868

United States, New Mexico

University of New Mexico Medical Center

Albuquerque, New Mexico, United States, 87131

United States, North Carolina

Duke University Medical Center

Durham, North Carolina, United States, 27710

Forsyth Medical Center

Winston-Salem, North Carolina, United States, 27103

United States, Pennsylvania

Temple University Hospital

Philadelphia, Pennsylvania, United States, 19140

United States, South Carolina

Greenville Hospital System

Greenville, South Carolina, United States, 29605

United States, Tennessee

University of Tennesse Medical Center

Knoxville, Tennessee, United States, 37920

United States, Texas

University of Texas Health Sciences Center at Houston

Houston, Texas, United States, 77030

Sponsors and Collaborators

Ferring Pharmaceuticals

Investigators

• Study Director: Clinical Development Support; Ferring Pharmaceuticals

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00828711
• Other Study ID Numbers: Miso-Obs-204
• First Posted: January 26, 2009
• Results First Posted: April 21, 2014
• Last Update Posted: April 21, 2014
• Last Verified: March 2014

Keywords provided by Ferring Pharmaceuticals:

Misoprostol vaginal insert; Induction of labor; Cervical ripening; Rate of cesarean section