Pharmacokinetic (PK) Study of the 200 Microgram (mcg) Misoprostol Vaginal Insert (MVI 200) in Women at Term Gestation (The MVI-PK Study)

Study Overview
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Brief Summary
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The purpose of this study is to determine the pharmacokinetics (PK) of misoprostol acid for the MVI 200 in women requiring cervical ripening and induction of labor.

Official Title
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A Multicenter, Open-Label, Phase II Study of the 200 mcg Misoprostol Vaginal Insert (MVI 200) to Obtain Pharmacokinetics in Women at Term Gestation (The MVI-PK Study)

Conditions
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Cervical Ripening, Induction of Labor

Intervention / Treatment
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* 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: Women with hemoglobin level < 10.0 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 congenital anomalies, not including polydactyly; Any evidence of fetal compromise at baseline (e.g., non-reassuring fetal heart rate pattern or meconium staining); Amnioinfusion or other treatment of non-reassuring fetal status at any time prior to the induction attempt; 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: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 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 |
| --- | --- | --- |
| Time of Maximum Plasma Concentration (Tmax) of Misoprostol After Insertion | The timepoints over which the pharmacokinetic measurements were assessed, and deemed as accurate and appropriate, were as follows: 0 hours (baseline), 0.5,1, 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 and 1 hour after removal of the study drug. The 10 hour and 14 hour blood samples were obtained if the subject still had the study drug in place at those timepoints. | From study drug insertion up to 1 hour post study drug removal. | 
| Maximum Plasma Concentration (Cmax) of Misoprostol up to 1 Hour 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), 0.5,1, 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 and 1 hour after removal of the study drug. The 10 hour and 14 hour blood samples were obtained if the subject still had the study drug in place at those timepoints. | From study drug insertion up to 1 hour post study drug removal | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pharmacokinetics, Misoprostol Vaginal Insert, Induction of labor, Cervical Ripening, Rate of Cesarean section