EXPEDITE: Efficacy & Safety Study Comparing Misoprostol Vaginal Insert (MVI) Versus Dinoprostone Vaginal Insert (DVI) for Reducing Time to Vaginal Delivery

• Sponsor: Ferring Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01127581
• Collaborator: (none)
• Enrollment: 1,358
• Locations: 34
• Arms: 2
• Duration (Months): 18
• Patients Per Site: 39.9
• Patients Per Site Per Month: 2.2

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the Misoprostol Vaginal Insert (MVI) 200 microgram (mcg) can decrease the time to vaginal delivery compared to the Dinoprostone Vaginal Insert (DVI) 10 milligram (mg) in pregnant women requiring cervical ripening and induction of labor.

Condition or Disease	Intervention/Treatment	Phase
Reducing Time to Vaginal Delivery; Cervical Ripening; Induction of Labor	Drug: MVI 200; Drug: Dinoprostone Vaginal Insert (DVI)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 1358 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Phase III, Double-blind, Randomized, Multicenter Study of Exogenous Prostaglandin Comparing the Efficacy & Safety of the MVI 200 mcg Versus the Dinoprostone Vaginal Insert (DVI) for Reducing Time to Vaginal Delivery in Pregnant Women at Term
• Study Start Date: Sep 1, 2010
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Mar 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
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)
Active Comparator: Dinoprostone Vaginal Insert (DVI) 10 mg Dinoprostone vaginal insert	Drug: Dinoprostone Vaginal Insert (DVI); Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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: Cervidil (R) Propess (R)

Outcome Measures

Primary Outcome Measures

1. Time to Vaginal Delivery During the First Hospital Admission [Interval from study drug administration to vaginal delivery (average 24 hours)]

2. Incidence of Cesarean Delivery During the First Hospital Admission [Interval from study drug administration to cesarean delivery (average 24 hours)]

Secondary Outcome Measures

1. Time to Any Delivery (Vaginal or Cesarean) During the First Hospital Admission [Interval from study drug administration to neonate delivery (average 24 hours)]

2. Time to Active Labor During the First Hospital Admission [Interval from study drug administration to active labor (average 12 hours)]

   Active labor was defined as progressive cervical dilatation to 4 cm with any frequency of contractions OR rhythmic, firm, adequate quality uterine contractions causing progressive cervical change occurring at a frequency of 3 or more in 10 minutes and lasting 45 seconds or more.

3. Incidence of Pre-delivery Oxytocin During the First Hospital Admission [At least 30 minutes after study drug removal]

   Percentage of participants in receipt of Oxytocin for induction after study drug removal.

4. Incidence of Vaginal Delivery Within 12 Hours [Interval from study drug administration to vaginal delivery within 12 hours]

5. Incidence of Any Delivery Within 24 Hours [Interval from study drug administration to delivery of neonate within 24 hours]

6. Incidence of Any Delivery Within 12 Hours [Interval from study drug administration to delivery of neonate within 12 hours]

7. Incidence of Vaginal Delivery Within 24 Hours [Interval from study drug administration to vaginal delivery within 24 hours]

8. Incidence of Vaginal Delivery [Interval from study drug administration to vaginal delivery (average 24 hours)]

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts 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 pharmacological 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 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, dinoprostone, other prostaglandins or any of the excipients;

• Any condition urgently requiring delivery;

• Unable to comply with the protocol.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Maricopa Medical Center - District Medical Group	Phoenix	Arizona	United States
2	Precision Trials	Phoenix	Arizona	United States
3	Phoenix Perinatal Associates (Scottsdale Healthcare Shea)	Scottsdale	Arizona	United States
4	Watching Over Mothers and Babies Foundation	Tucson	Arizona	United States
5	Miller's Childrens Hospital	Long Beach	California	United States
6	UCI Medical Center	Orange	California	United States
7	The Women's Clinic of Northern Colorado	Fort Collins	Colorado	United States
8	Christiana Care Health System (DE Center for MFM)	Newark	Delaware	United States
9	University of FL College of Medicine	Jacksonville	Florida	United States
10	Altus Research	Lake Worth	Florida	United States
11	University of South Florida	Tampa	Florida	United States
12	Indiana University School of Medicine	Indianapolis	Indiana	United States
13	University of Kansas School of Medicine	Kansas City	Kansas	United States
14	University of Michigan Hospital	Ann Arbor	Michigan	United States
15	Spectrum Health	Grand Rapids	Michigan	United States
16	St. Louis University	St. Louis	Missouri	United States
17	St. Peters University Hospital	New Brunswick	New Jersey	United States
18	University of New Mexico/New Mexico Health Science Center	Albuquerque	New Mexico	United States
19	Duke University Medical Center	Durham	North Carolina	United States
20	East Carolina University, Brody School of Medicine	Greenville	North Carolina	United States
21	Lyndhurst Gynecologic Associates	Winston-Salem	North Carolina	United States
22	University of Cincinnati	Cincinnati	Ohio	United States
23	Clinical Trials of America	Eugene	Oregon	United States
24	Drexel University College of Medicine	Philadelphia	Pennsylvania	United States
25	Temple University School of Medicine	Philadelphia	Pennsylvania	United States
26	Thomas Jefferson University	Philadelphia	Pennsylvania	United States
27	Medical University of South Carolina	Charleston	South Carolina	United States
28	University Medical Group/Greenville Hospital System	Greenville	South Carolina	United States
29	UT College of Medicine Chattanooga, Erlanger Health System	Chattanooga	Tennessee	United States
30	High Risk Obstetrical Consultants, PLLC	Knoxville	Tennessee	United States
31	Research Memphis Associates	Memphis	Tennessee	United States
32	University of Texas Health Sciences Center at Houston	Houston	Texas	United States
33	Salt Lake Women's Center, PC	Sandy	Utah	United States
34	Marshfield Clinic Research Foundation	Marshfield	Wisconsin	United States

Sponsors and Collaborators

• Ferring Pharmaceuticals

Investigators

• Study Director: Clinical Development Support, Ferring Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ferring Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01127581
• Other Study ID Numbers: Miso-Obs-303
• First Posted: May 21, 2010
• Last Update Posted: May 1, 2014
• Last Verified: Apr 1, 2014

• Keywords provided by Ferring Pharmaceuticals: Misoprostol vaginal insert; Dinoprostone vaginal insert; Cervidil; Cervical ripening; Induction of labor; Rate of cesarean section
• Additional relevant MeSH terms: Dinoprostone

Study Results

Participant Flow

Recruitment Details	Pregnant women who required to be induced were recruited at 35 sites in the US.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Period Title: Overall Study
STARTED	678	680
COMPLETED	678	680
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)	Total
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.	Total of all reporting groups
Overall Participants	678	680	1358
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	678 100%	680 100%	1358 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.2 (5.99)	25.9 (5.95)	26.0 (5.96)
Sex: Female, Male (Count of Participants)
Female	678 100%	680 100%	1358 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	678 100%	680 100%	1358 100%

Outcome Measures

1. Primary Outcome

Title	Time to Vaginal Delivery During the First Hospital Admission
Time Frame	Interval from study drug administration to vaginal delivery (average 24 hours)

Outcome Measure Data

Analysis Population Description

Subjects who underwent a cesarean delivery during the first hospitalization were censored using the longest time interval from study drug administration to cesarean delivery, independent of treatment assignment. Subjects who were discharged prior to delivery or withdrew consent prior to delivery were also censored.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Median (95% Confidence Interval) [minutes]	1292.00	1968.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	Subjects who underwent a cesarean delivery during the first hospitalization were censored using the longest time interval from study drug administration to cesarean delivery during the first hospitalization, independent of treatment group. Subjects who, in their first hospitalization, were discharged prior to delivery or withdrew consent prior to delivery were censored using the longest time interval from study drug administration to labor and delivery discharge, independent of treatment group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-677
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	Sample size 675 per group provides 90% power to see an improvement of ≥320 minutes (20% improvement from DVI) in time to vaginal delivery between MVI 200 & DVI assuming a median time of 1600 minutes for DVI & 34% dropout rate based on 5% 2-sided test

2. Primary Outcome

Title	Incidence of Cesarean Delivery During the First Hospital Admission
Time Frame	Interval from study drug administration to cesarean delivery (average 24 hours)

Outcome Measure Data

Analysis Population Description

Analysis was based on a between-treatment-group difference in the safety population. Subjects discharged prior to delivery, withdrew early without having a cesarean delivery or were lost-to-follow up were classified as not having the event.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Number (95% Confidence Interval) [percentage of participants]	25.96 3.8%	27.06 4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	The analysis of the cesarean delivery rates during the first hospitalization was based on a between-treatment-group difference. If the upper limit of the asymptotic two-sided 95% confidence interval of the difference in event rates (MVI minus DVI) was less than the calculated non-inferiority margin (10% relative to the DVI rate, i.e., 0.1 times DVI rate), then MVI 200 would be considered non-inferior to DVI.
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	A sample size of 675 subjects per group will provide a sufficient number of subjects to assess non-inferiority of MVI 200 with respect to rate of cesarean delivery, based on an alpha level of 5% and 80% power for a two-sided approach using a 10% non-inferiority limit (relative to the DVI rate), assuming a 30% rate of cesarean delivery in the DVI group compared to a 26% rate in the MVI 200 group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Populations
	Estimated Value	-1.10
	Confidence Interval	(2-Sided) 95%; -5.79 to 3.59
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

3. Secondary Outcome

Title	Time to Any Delivery (Vaginal or Cesarean) During the First Hospital Admission
Time Frame	Interval from study drug administration to neonate delivery (average 24 hours)

Outcome Measure Data

Analysis Population Description

Subjects who did not deliver during the first hospitalization were censored at the time of labour and delivery discharge.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Median (95% Confidence Interval) [minutes]	1096.50	1639.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	Subjects who did not deliver during the first hospitalization were censored using the longest time interval from study drug administration to labor and delivery discharge without delivery, independent of treatment group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-543
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

4. Secondary Outcome

Title	Time to Active Labor During the First Hospital Admission
Description	Active labor was defined as progressive cervical dilatation to 4 cm with any frequency of contractions OR rhythmic, firm, adequate quality uterine contractions causing progressive cervical change occurring at a frequency of 3 or more in 10 minutes and lasting 45 seconds or more.
Time Frame	Interval from study drug administration to active labor (average 12 hours)

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Median (95% Confidence Interval) [minutes]	726.50	1116.50

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments	Subjects who never went into active labor during the first hospitalization were censored using the longest time interval from study drug administration to delivery during the first hospitalization, independent of treatment group. Subjects who, in their first hospitalization, were discharged prior to delivery or withdrew consent prior to delivery were censored using the longest time interval from study drug administration to labor and delivery discharge, independent of treatment group.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	-390
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

5. Secondary Outcome

Title	Incidence of Pre-delivery Oxytocin During the First Hospital Admission
Description	Percentage of participants in receipt of Oxytocin for induction after study drug removal.
Time Frame	At least 30 minutes after study drug removal

Outcome Measure Data

Analysis Population Description

Analysis population includes subjects who delivered during the first hospitalization.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	674	671
Number (95% Confidence Interval) [percentage of participants]	48.1 7.1%	74.1 10.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	-26
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

6. Secondary Outcome

Title	Incidence of Vaginal Delivery Within 12 Hours
Time Frame	Interval from study drug administration to vaginal delivery within 12 hours

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Number (95% Confidence Interval) [percentage of participants]	19.76 2.9%	8.38 1.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	9.67
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

7. Secondary Outcome

Title	Incidence of Any Delivery Within 24 Hours
Time Frame	Interval from study drug administration to delivery of neonate within 24 hours

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) Population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Number (95% Confidence Interval) [percentage of participants]	67.70 10%	40.74 6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	26.96
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

8. Secondary Outcome

Title	Incidence of Any Delivery Within 12 Hours
Time Frame	Interval from study drug administration to delivery of neonate within 12 hours

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) Population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Number (95% Confidence Interval) [percentage of participants]	23.16 3.4%	9.26 1.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	13.90
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

9. Secondary Outcome

Title	Incidence of Vaginal Delivery Within 24 Hours
Time Frame	Interval from study drug administration to vaginal delivery within 24 hours

Outcome Measure Data

Analysis Population Description

Intention-to-Treat (ITT) Population

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Number (95% Confidence Interval) [percentage of participants]	54.57 8%	33.97 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	29.80
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

10. Secondary Outcome

Title	Incidence of Vaginal Delivery
Time Frame	Interval from study drug administration to vaginal delivery (average 24 hours)

Outcome Measure Data

Analysis Population Description

The Intention-to-Treat (ITT) population was used for all secondary efficacy analyses.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Number (95% Confidence Interval) [percentage of participants]	73.30 10.8%	71.62 10.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	MVI 200, Dinoprostone Vaginal Insert (DVI)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Fisher Exact
	Comments
Method of Estimation	Estimation Parameter	Difference in Proportions
	Estimated Value	1.68
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments	MVI 200 - DVI

11. Secondary Outcome

Title	Rate of Adverse Events
Description	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.
Time Frame	From study drug administration to hospital discharge (approximately 48-72 hours)

Outcome Measure Data

Analysis Population Description

The percentage of subjects with adverse events are presented for the Intrapartum (before delivery), postpartum (maternal) and neonatal periods.

Arm/Group Title	MVI 200	Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.	10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
Measure Participants	678	680
Subjects with an Intrapartum Adverse Events	55.5 8.2%	54.6 8%
Subjects with Maternal Postpartum Adverse Events	21.4 3.2%	21.2 3.1%
Subjects with Neonatal Adverse Events	53.4 7.9%	58.1 8.5%

Adverse Events

Time Frame	All adverse events were followed until resolution or at least 30 days after discontinuation of the study drug, whichever occurred first.
Adverse Event Reporting Description	All adverse events occurring to the maternal-fetal unit (pre-delivery/ intrapartum), the mother (postpartum) or the neonate were recorded. Adverse events that resulted in a cesarean delivery were reported as serious adverse events as they were medically significant events that routinely prolonged the duration of hospitalization.
Arm/Group Title	MVI 200		Dinoprostone Vaginal Insert (DVI)
Arm/Group Description	MVI 200 mcg vaginal insert 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.		10 mg Dinoprostone vaginal insert Dinoprostone vaginal insert: Dose reservoir of 10 mg of dinoprostone in a hydrogel polymer vaginal insert within a retrieval system. The DVI 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.
All Cause Mortality
	MVI 200		Dinoprostone Vaginal Insert (DVI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	MVI 200		Dinoprostone Vaginal Insert (DVI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	130/678 (19.2%)		107/680 (15.7%)
Blood and lymphatic system disorders
Disseminated intravascular coagulation #	1/678 (0.1%)	1	0/680 (0%)	0
Polycythaemia *	1/678 (0.1%)	1	0/680 (0%)	0
Cardiac disorders
Pericarditis #	0/678 (0%)	0	1/680 (0.1%)	1
Supraventricular tachycardia *	1/678 (0.1%)	1	0/680 (0%)	0
Supraventricular tachycardia +	0/678 (0%)	0	1/680 (0.1%)	1
Congenital, familial and genetic disorders
Adrenogenital syndrome *	1/678 (0.1%)	1	0/680 (0%)	0
Anal atresia *	0/678 (0%)	0	1/680 (0.1%)	1
Ankyloglossia congenital *	3/678 (0.4%)	3	2/680 (0.3%)	2
Anomalous pulmonary venous connection *	1/678 (0.1%)	1	0/680 (0%)	0
Atrial septal defect *	8/678 (1.2%)	8	6/680 (0.9%)	6
Cataract congenital *	0/678 (0%)	0	1/680 (0.1%)	1
Congenital choroid plexus cyst *	1/678 (0.1%)	1	0/680 (0%)	0
Congenital hydronephrosis *	0/678 (0%)	0	1/680 (0.1%)	1
Congenital nose malformation *	0/678 (0%)	0	1/680 (0.1%)	1
Congenital pyelocaliectasis *	1/678 (0.1%)	1	1/680 (0.1%)	1
Cryptorchism *	6/678 (0.9%)	6	2/680 (0.3%)	2
Hydrocele *	1/678 (0.1%)	1	1/680 (0.1%)	1
Hypospadias *	4/678 (0.6%)	4	4/680 (0.6%)	4
Patent ductus arteriosus *	4/678 (0.6%)	4	4/680 (0.6%)	4
Penile torsion *	3/678 (0.4%)	3	1/680 (0.1%)	1
Phimosis *	0/678 (0%)	0	3/680 (0.4%)	3
Pilonidal cyst congenital *	3/678 (0.4%)	3	7/680 (1%)	7
Polydactyly *	3/678 (0.4%)	3	3/680 (0.4%)	3
Pulmonary artery stenosis congenital *	1/678 (0.1%)	1	0/680 (0%)	0
Supernumerary nipple *	0/678 (0%)	0	2/680 (0.3%)	2
Syndactyly *	1/678 (0.1%)	1	0/680 (0%)	0
Talipes *	1/678 (0.1%)	1	0/680 (0%)	0
VACTERL syndrome *	2/678 (0.3%)	2	0/680 (0%)	0
Ventricular septal defect *	4/678 (0.6%)	4	1/680 (0.1%)	1
Eye disorders
Vitreous haemorrhage *	0/678 (0%)	0	1/680 (0.1%)	1
Gastrointestinal disorders
Anal fistula *	0/678 (0%)	0	1/680 (0.1%)	1
Intestinal obstruction *	1/678 (0.1%)	1	0/680 (0%)	0
Salivary gland enlargement *	1/678 (0.1%)	1	0/680 (0%)	0
General disorders
Fever neonatal *	1/678 (0.1%)	1	0/680 (0%)	0
Infections and infestations
Endometritis #	2/678 (0.3%)	2	1/680 (0.1%)	1
Pneumonia *	0/678 (0%)	0	1/680 (0.1%)	1
Pneumonia #	0/678 (0%)	0	1/680 (0.1%)	1
Postpartum sepsis #	1/678 (0.1%)	1	0/680 (0%)	0
Sepsis neonatal *	1/678 (0.1%)	1	1/680 (0.1%)	1
Septic shock *	0/678 (0%)	0	1/680 (0.1%)	1
Injury, poisoning and procedural complications
Skull fracture *	1/678 (0.1%)	1	0/680 (0%)	0
Investigations
Urine output decreased *	1/678 (0.1%)	1	1/680 (0.1%)	1
Metabolism and nutrition disorders
Feeding disorder neonatal *	1/678 (0.1%)	1	2/680 (0.3%)	2
Musculoskeletal and connective tissue disorders
Joint crepitation *	1/678 (0.1%)	1	1/680 (0.1%)	1
Muscular weakness #	0/678 (0%)	0	1/680 (0.1%)	1
Nervous system disorders
Dysaesthesia #	1/678 (0.1%)	1	0/680 (0%)	0
Encephalopathy neonatal *	0/678 (0%)	0	1/680 (0.1%)	1
Hypoxic-ischaemic encephalopathy *	4/678 (0.6%)	4	0/680 (0%)	0
Paraesthesia #	0/678 (0%)	0	1/680 (0.1%)	1
Pregnancy, puerperium and perinatal conditions
Abnormal labour affecting foetus +	13/678 (1.9%)	13	0/680 (0%)	0
Drug withdrawal syndrome neonatal *	1/678 (0.1%)	1	1/680 (0.1%)	1
Erb's palsy *	0/678 (0%)	0	1/680 (0.1%)	1
Foetal acidosis *	1/678 (0.1%)	1	0/680 (0%)	0
Foetal heart rate disorder +	65/678 (9.6%)	65	46/680 (6.8%)	46
Hypoglycaemia neonatal *	3/678 (0.4%)	3	2/680 (0.3%)	2
Neonatal disorder *	1/678 (0.1%)	1	0/680 (0%)	0
Postpartum haemorrhage #	2/678 (0.3%)	2	3/680 (0.4%)	3
Premature separation of placenta +	1/678 (0.1%)	1	0/680 (0%)	0
Puerperal pyrexia #	1/678 (0.1%)	1	0/680 (0%)	0
Retained placenta or membranes #	0/678 (0%)	0	1/680 (0.1%)	1
Uterine contractions abnormal +	1/678 (0.1%)	1	0/680 (0%)	0
Uterine rupture +	1/678 (0.1%)	1	0/680 (0%)	0
Weight decrease neonatal *	1/678 (0.1%)	1	1/680 (0.1%)	1
Psychiatric disorders
Anxiety #	0/678 (0%)	0	1/680 (0.1%)	1
Renal and urinary disorders
Hydronephrosis *	0/678 (0%)	0	1/680 (0.1%)	1
Reproductive system and breast disorders
Chordee *	1/678 (0.1%)	1	0/680 (0%)	0
Testicular torsion *	0/678 (0%)	0	1/680 (0.1%)	1
Vulval haematoma #	0/678 (0%)	0	1/680 (0.1%)	1
Respiratory, thoracic and mediastinal disorders
Neonatal aspiration *	1/678 (0.1%)	1	2/680 (0.3%)	2
Neonatal respiratory depression *	0/678 (0%)	0	1/680 (0.1%)	1
Neonatal respiratory distress syndrome *	0/678 (0%)	0	1/680 (0.1%)	1
Pneumothorax *	0/678 (0%)	0	1/680 (0.1%)	1
Transient tachypnoea of the newborn *	1/678 (0.1%)	1	0/680 (0%)	0
Vascular disorders
Deep vein thrombosis #	1/678 (0.1%)	1	0/680 (0%)	0
Hypertension #	1/678 (0.1%)	1	1/680 (0.1%)	1
Other (Not Including Serious) Adverse Events
	MVI 200		Dinoprostone Vaginal Insert (DVI)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	520/678 (76.7%)		533/680 (78.4%)
Pregnancy, puerperium and perinatal conditions
Abnormal labour affecting foetus +	59/678 (8.7%)	62	19/680 (2.8%)	19
Arrested labour +	96/678 (14.2%)	96	128/680 (18.8%)	129
Caput succedaneum *	58/678 (8.6%)	58	60/680 (8.8%)	60
Chorioamnionitis +	38/678 (5.6%)	38	59/680 (8.7%)	59
Foetal heart rate disorder +	124/678 (18.3%)	138	138/680 (20.3%)	160
Hyperbilirubinaemia neonatal *	62/678 (9.1%)	62	78/680 (11.5%)	78
Meconium in amniotic fluid +	120/678 (17.7%)	120	92/680 (13.5%)	92
Postpartum haemorrhage #	40/678 (5.9%)	41	37/680 (5.4%)	37
Umbilical cord around neck *	184/678 (27.1%)	184	194/680 (28.5%)	194
Respiratory, thoracic and mediastinal disorders
Neonatal respiratory depression *	34/678 (5%)	34	30/680 (4.4%)	30
Surgical and medical procedures
Infection prophylaxis *	46/678 (6.8%)	46	63/680 (9.3%)	63

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Any abstract,presentation or manuscript proposed for publication must be submitted to the Sponsor for review at least 30 days prior to submission for any meeting or journal.If deemed necessary by the Sponsor for protection of proprietary information prior to patent filing,the Investigator agrees to a further delay of 60 days before any presentation or publication is submitted.Publications must be in a form that does not reveal technical information that is considered confidential or proprietary.