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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Cervical Ripening, Induction of Labor

Intervention / Treatment
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* Drug: MVI 100
* Drug: MVI 150
* Drug: MVI 200


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MVI 100<br>MVI 100 mcg vaginal insert | Drug: MVI 100<br>* 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.<br>* Other names: Misodel (R);|
| Experimental: MVI 150<br>MVI 150 mcg vaginal insert | Drug: MVI 150<br>* 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.<br>* Other names: Misodel (R);|
| Experimental: MVI 200<br>MVI 200 mcg vaginal insert | Drug: MVI 200<br>* 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.<br>* Other names: Misodel (R);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Misoprostol vaginal insert, Induction of labor, Cervical ripening, Rate of cesarean section