Cervical Ripening, Induction of Labor
Conditions
Keywords
Pharmacokinetics, Misoprostol Vaginal Insert, Induction of labor, Cervical Ripening, Rate of Cesarean section
Brief summary
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.
Interventions
DRUGMVI 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.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time of Maximum Plasma Concentration (Tmax) of Misoprostol After Insertion | From study drug insertion 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. |
| Maximum Plasma Concentration (Cmax) of Misoprostol up to 1 Hour Post Study Drug Removal | From study drug insertion 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Adverse Events. | 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. |
Countries
United States
Participant flow
Recruitment details
Pregnant women who required to be induced were recruited at 1 site in the US
Participants by arm
| Arm | Count |
|---|---|
| MVI 200 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. | 24 |
| Total | 24 |
Baseline characteristics
| Characteristic | MVI 200 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants |
| Age, Continuous | 28.0 years STANDARD_DEVIATION 6.33 |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 16 / 24 |
| serious Total, serious adverse events | 5 / 24 |
Outcome results
Primary
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.
Time frame: From study drug insertion up to 1 hour post study drug removal
Population: The pharmacokinetic (PK) analysis included all 24 subjects from the Intention-to-Treat (ITT) population.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| MVI 200 | Maximum Plasma Concentration (Cmax) of Misoprostol up to 1 Hour Post Study Drug Removal | 45.8 pg/mL | Standard Deviation 25.7 |
Primary
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.
Time frame: From study drug insertion up to 1 hour post study drug removal.
Population: The pharmacokinetic (PK) analysis included all 24 subjects from the Intention-to-Treat (ITT) population.
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| MVI 200 | Time of Maximum Plasma Concentration (Tmax) of Misoprostol After Insertion | 4 hours | Standard Deviation 2.09 |
Secondary
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.
Time frame: From study drug administration to hospital discharge (approximately 48-72 hours).
Population: The percentage of subjects with adverse events are presented for the Intrapartum (before delivery), postpartum (maternal) and neonatal periods.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MVI 200 | Rate of Adverse Events. | Subjects with Intrapartum Adverse Events | 66.7 percentage of participants |
| MVI 200 | Rate of Adverse Events. | Subjects with Maternal Postpartum Adverse Events | 8.3 percentage of participants |
| MVI 200 | Rate of Adverse Events. | Subjects with Neonatal Adverse Events | 50.0 percentage of participants |