Efficacy and safety of ebopiprant to delay preterm birth after oral administration in pregnant women with spontaneous preterm labor receiving atosiban: a phase 2a, double-blind, parallel group, randomized, placebo-controlled, proof of concept study

Objective: To assess the efficacy and safety of ebopiprant (OBE022), a novel, oral and selective prostaglandin F2α (PGF2α) receptor antagonist, to delay spontaneous preterm labor. Methods: This randomized, placebo-controlled, double-blind study (NCT03369262) was conducted between January 2019 and March 2020 in large referral maternity hospitals across Czech Republic, Finland, Israel, Russia, Spain, and Vietnam. Enrolled participants had spontaneous preterm labor at a gestational age of 24–34 weeks, with ≥4 contractions/30 min, cervical dilatation of 1–4 cm, and ≥1 other sign of preterm labor (cervical length ≤25 mm, progressive cervical change, or a positive test [insulin-like growth factor-binding protein-1 or fetal fibronectin] for preterm labor). All participants were administered atosiban infusion for 48 h. Participants were randomized and initiated treatment with ebopiprant or placebo ≤24 h after starting atosiban. Participants received ebopiprant 1000 mg or placebo loading dose on Day 1 followed by a maintenance dose of 500 mg twice a day 12 h apart for 7 days. The main study outcomes were observed rate of delivery within 48 h or 7 days after initiation of ebopiprant vs placebo and maternal, fetal, and neonatal safety. Results: A total of 113 participants (83 with singletons, 30 with twins) were randomized. Delivery within 48 h occurred in 12.5 % (7/56) participants in the ebopiprant group versus 21.8 % (12/55) in the placebo group [adjusted odds ratio 0.52 [90 % confidence interval, 0.22–1.23]). This possible difference was observed for singleton (12.5 % versus 26.8 %) but not for twin (12.5 % versus 7.1 %) births. At 7 days after randomization, no difference in delivery rates was observed. The incidence of maternal, fetal and neonatal adverse events was comparable between the treatment groups. Conclusions: Ebopiprant added to atosiban infusion may reduce the probability of delivering within 48 h.