Determining dose and endpoints of a controlled-release misoprostol vaginal insert for a phase III trial

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.

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

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.

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.