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

• Time to vaginal delivery [ Time Frame: Interval from insertion to delivery ] [ Designated as safety issue: No ]
• Adverse Events [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
• Proportion of cesarean delivery [ Time Frame: after insertion of study drug ] [ Designated as safety issue: Yes ]
• Cervical ripening using composite measure of success [ Time Frame: 6, 12, 18 and 24h after insertion of drug ] [ Designated as safety issue: No ]
• Vaginal delivery [ Time Frame: Within 12h after drug insertion ] [ Designated as safety issue: No ]
• Use of oxytocin [ Time Frame: after study drug removal ] [ Designated as safety issue: No ]
• pharmacokinetics [ Time Frame: During study drug insertion and after removal ] [ Designated as safety issue: No ]
• Time to Onset of Active Labor [ Time Frame: After insertion of study drug ] [ Designated as safety issue: No ]

• Time to vaginal delivery [ Time Frame: Interval from insertion to delivery ] [ Designated as safety issue: No ]
• Adverse Events [ Time Frame: 72 hours ] [ Designated as safety issue: Yes ]
• Proportion of cesarean delivery [ Time Frame: after insertion of study drug ] [ Designated as safety issue: Yes ]
• Cervical ripening using composite measure of success [ Time Frame: 6, 12, 18 and 24h after insertion of drug ] [ Designated as safety issue: No ]
• Vaginal delivery [ Time Frame: Within 12h after drug insertion ] [ Designated as safety issue: No ]
• Use of oxytocin [ Time Frame: after study drug removal ] [ Designated as safety issue: No ]
• pharmacokinetics [ Time Frame: During study drug insertion and after removal ] [ Designated as safety issue: No ]

Randomized, double blind, dose ranging study to assess the efficacy and safety of up to 24 hours treatment with the MVI 100, MVI 150 and MVI 200. Oxytocin may be used after removal of the study medication. There must be at least a 30 minute waiting interval between removing the study drug and commencing oxytocin. Patients will be stratified by parity and center. During treatment, women will be assessed for safety, onset of labor, and cervical ripening. Fetal heart rate patterns and uterine activity will be assessed via continuous CTG monitoring. Time to and mode of delivery of the neonate will be recorded. Modified Bishop score will be assessed at 6, 12, 18 and 24 hours after study drug insertion.

• Cervical Ripening
• Induction of Labor

• Drug: MVI 100
  Hydrogel polymer vaginal insert with retrieval system, one 100 mcg insert for induction of labor, kept in place a maximum of 24h.
  Other Names:

  • Misoprostol Vaginal Insert
  • MVI
  • Misopess
  • Misodel
• Drug: MVI 150
  Hydrogel polymer vaginal insert with retrieval system, one 150 mcg insert for induction of labor, kept in place a maximum of 24h.
  Other Names:

  • Misoprostol vaginal insert
  • MVI
  • Misopess
  • Misodel
• Drug: MVI 200
  Hydrogel polymer vaginal insert with retrieval system, one 200 mcg insert for induction of labor, kept in place a maximum of 24h.
  Other Names:

  • Misoprostol vaginal insert
  • MVI
  • Misopess
  • Misodel

• Experimental: MVI 100
  MVI 100 mcg vaginal insert
  Intervention: Drug: MVI 100
• Experimental: MVI 150
  MVI 150 mcg vaginal insert
  Intervention: Drug: MVI 150
• Experimental: MVI 200
  MVI 200 mcg vaginal insert
  Intervention: Drug: MVI 200

Inclusion Criteria:

• Pregnant women at ≥ 36 weeks 0 days inclusive gestation;
• 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);
• BMI ≤ 50 at the time of entry to the study;
• Written informed consent.

Exclusion Criteria:

• Nulliparous women participating in the PK arm of the study: women with hemoglobin level < 11.0 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 HELLP syndrome, other end-organ affliction or 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.