Determining dose and endpoints of a controlled-release misoprostol vaginal insert for a phase III trial.
OBJECTIVE
To determine phase III study design using the phase II data for a proprietary controlled-release misoprostol vaginal insert for cervical ripening and labor induction.


METHODS
The reported experiences in 2 phase II trials involving induction of labor in 168 women are discussed.


RESULTS
Combining data from 2 phase II studies, we reported a median induction to vaginal delivery interval of <15 hours regardless of parity using the 100-microg insert. This misoprostol vaginal insert was well tolerated with few maternal systemic effects. Uterine hyperstimulation occurred in <5% of cases in the 100-microg and lesser dose groups. Hyperstimulation syndrome attributed to insert led to cesarean delivery in 1 (2.4%) subject in the 200-microg and 2 (33.3%) in the 300-microg dose groups. The lowest cesarean rates were 4.7% (2 of 43) in the 100-microg group and 5.7% (2 of 35) in the 50-microg group.


CONCLUSIONS
Misoprostol vaginal 50-microg and 100-microg inserts had acceptable efficacy and safety profiles, and we agreed to test these doses in a randomized phase III multicenter study using dinoprostone (Cervidil, Forest Pharmaceuticals, St. Louis, Missouri), a dinoprostone vaginal insert, as the blinded comparator.
Department of Obstetrics and Gynecology, University of California, Irvine, Irvine, California, USA. dwing@uci.edu
Deborah A
DA
Wing
Barbara L
BL
Powers
William F
WF
Rayburn
D000282:Administration, Intravaginal; D020070:Cervical Ripening; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D004305:Dose-Response Relationship, Drug; D017277:Drug Approval; D005260:Female; D006801:Humans; D016595:Misoprostol / Q000008:administration & dosage* / Q000009:adverse effects; D010120:Oxytocics / Q000008:administration & dosage* / Q000009:adverse effects; D010298:Parity; D011247:Pregnancy; D016032:Randomized Controlled Trials as Topic; D014481:United States
D010120:Oxytocics; D016595:Misoprostol