350: A multicenter, randomized, double-blind, placebo-controlled phase 2 trial of retosiban, a selective oxytocin receptor antagonist, for the management of preterm labor

To determine the efficacy and safety of retosiban given to women in spontaneous preterm labor (SPTL). Women with a singleton pregnancy in SPTL between 30 0/7 and 35 6/7 weeks, stratified by gestational age, were randomized to 48h treatment with intravenous (IV) retosiban or placebo. SPTL was defined as contraction rate ≥4/0.5h or ≥6/h and cervical dilatation ≥1 cm and ≤4 cm. Antenatal steroids and rescue tocolytics were permitted. A Bayesian analysis was used to compare groups for days to delivery, preterm births (PTB) prior to 37 weeks, and percent of women achieving uterine quiescence (≤4 contractions/h with no change in cervical dilation >1cm at 5-6h). Median baseline cervical dilation was 2.0 cm for both groups. Uterine quiescence at 5-6h was 62% and 41%, respectively, for the retosiban and placebo groups (RR 1.53, [CI* 0.98, 2.48]). Number of placebo subjects receiving rescue tocolysis was twice that of the retosiban group. Retosiban increased days to delivery by a mean of 8.2 days relative to placebo (95% CI* 2.7, 13.7). This difference was consistent across gestational ages. The incidence of PTB in the retosiban group was 18.7% compared to 47.2% in the placebo group. The relative risk for PTB in the retosiban group was 0.38 (95% CI* [0.15, 0.81]). No births occurred within 7 days in the retosiban group compared with 6 (17.6%) births in the placebo group. Headache was reported more commonly in the retosiban group (14% vs 2%). Neonatal SAEs were consistent with complications of prematurity. Results from maternal, fetal and neonatal safety assessments were similar between groups. * CI = credible interval. Retosiban was associated with a significant increase in time to delivery and decrease in PTB in women with SPTL. The safety profile for IV retosiban over 48 hours appears favorable. These results support progression to Phase 3 studies.