Treatment of spontaneous preterm labour with retosiban: a phase 2 proof-of-concept study

  • Br J Clin Pharmacol. 2015 Oct;80(4):740-9. doi: 10.1111/bcp.12646.
Steven Thornton  1 ,  Hugh Miller  2 ,  Guillermo Valenzuela  3 ,  Jerry Snidow  4 ,  Brendt Stier  5 ,  Michael J Fossler  5 ,  Timothy H Montague  5 ,  Marcy Powell  4 ,  Kathleen J Beach  5
Affiliations
  • 1. University of Exeter Medical School, Exeter, UK.
  • 2. Watching Over Mothers and Babies Foundation, Tucson, AZ, USA.
  • 3. Arrowhead Regional Medical Center, Colton, CA, USA.
  • 4. GlaxoSmithKline, Research Triangle Park, NC, USA.
  • 5. GlaxoSmithKline, Philadelphia, PA, USA.
PMID: 25819462 DOI: 10.1111/bcp.12646
Abstract

Aim: The aim was to investigate the efficacy and safety of intravenous retosiban in women with spontaneous preterm labour.

Methods: This was a randomized, double-blind, placebo-controlled, phase 2 trial. Retosiban was administered intravenously for 48 h to women in spontaneous preterm labour between 30(0/7) and 35(6/7) weeks' gestation with an uncomplicated singleton pregnancy in an in-patient obstetric unit. Outcome measures were uterine quiescence (primary endpoint), days to delivery, preterm delivery and safety.

Results: Uterine quiescence was achieved in 62% of women who received retosiban (n = 30) compared with 41% who received placebo (n = 34). The relative risk (RR) was 1.53 (95% credible interval [CrI] 0.98, 2.48; NS). Retosiban resulted in a significant increase in time to delivery compared with placebo (mean difference 8.2 days, 95% CrI 2.7, 13.74). This difference was consistent across all gestational ages. The proportion of preterm births in the retosiban and placebo groups was 18.7% (95% CrI 7.4%, 33.7%) and 47.2% (95% CrI 31.4%, 63.4%), respectively. The RR of preterm birth in women treated with retosiban was 0.38 (95% CrI 0.15, 0.81). There were no deliveries within 7 days in the retosiban group, but there were six (17.6%) births in the placebo group. The maternal, fetal and neonatal adverse events were comparable in the retosiban and placebo groups.

Conclusions: Intravenous administration of retosiban in women with spontaneous preterm labour was associated with a greater than 1 week increase in time to delivery compared with placebo, a significant reduction in preterm deliveries, a non-significant increase in uterine quiescence and a favourable safety profile.

Keywords
preterm birth; preterm labour; proof-of-concept study; retosiban; uterine quiescence.
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