A Proof of Concept Study Assessing the Effect of Four Different Single Bolus Intravenous Doses of FE200440 and Placebo on Stopping Preterm Labor

• To determine the effects of four different single bolus doses of FE200440 administered intravenously on stopping preterm labour compared to placebo in pregnant women with advanced gestational age
• To establish the effects of four different single bolus doses of FE200440 administered intravenously on uterine contractions compared to placebo
• To evaluate the effects of four different single bolus doses of FE200440 administered intravenously on labour progression compared to placebo
• To establish the dose-response curve of single bolus doses of FE200440 administered intravenously in terms of time to delivery, uterine contractions and labour progression
• To determine the duration of action of four different single bolus doses of FE200440 administered intravenously in terms of time to delivery, uterine contractions and labour progression
• To establish the pharmacokinetic parameters of FE200440 after single bolus intravenous administration
• To determine the relation between plasma concentrations of FE200440 and uterine contractions and labour progression
• To compare the maternal, fetal and infant safety profile after intravenous administration of four different single bolus doses of FE200440 and placebo
• To evaluate the impact of four different single bolus doses of FE200440 administered intravenously on delivery outcome, postpartum events and lactation

Inclusion criteria

• Signed Informed Consent Form, prior to screening evaluations
• Mother and fetus in good general health
• Pregnant women age ≥ 18 years
• Gestational age (verified by early ultrasound or if an ultrasound is not available by Last Menstrual Period) between 34 weeks + 0 days and 35 weeks + 6 days (both days inclusive)
• At randomisation, there must be 6 or more uterine contractions of at least 30 seconds duration during a 30 minutes interval
• At randomisation, the cervical length must be ≤ 15 mm (by transvaginal ultrasound)
• At randomisation, the cervical dilatation must be >1 cm and <4 cm (by vaginal examination

Exclusion criteria

• Contraindications for the mother or the fetus to stop labour, including

• clinical suspicion of abruptio placenta
• known or suspected infection (e.g. urinary tract infection, chorioamnionitis)
• Controlled or uncontrolled diabetes mellitus (pre-gestational or gestational)
• Eclampsia or severe preeclampsia in the current pregnancy
• Previous major uterine surgery (e.g. myomectomy for leiomyomas), congenital uterine abnormalities, large leiomyomas, or retained intrauterine device
• Rupture of membrane in the current pregnancy
• Placenta praevia in the current pregnancy
• a)
• Oligohydramnios or polyhydramnios in the current pregnancy defined as amniotic fluid index (AFI) below 7.2 cm or above 27.8 cm
• Fetal weight (based on ultrasound) outside the ± 2SD limits provided in Appendix B
• Use of cervical cerclage in the current pregnancy
• Current multiple pregnancy
• Fetal death in utero in previous or current pregnancy
• Fetus with known or suspected abnormal karyotype or major malformations in the current pregnancy
• Abnormal fetal heart rate which the Investigator judges to reflect fetal distress
• Treatment with nifedipine, non-steroidal anti-inflammatory agents (NSAIDs) or intravenously administered magnesium sulphate for contractions during the current pregnancy or treatment with beta-mimetics, atosiban or progesterone within the last 7 days prior to randomisation
• Treatment with anticoagulation or fibrinolytic therapies prior to screening, or known or suspected or past history of thromboembolic disorders
• Known, suspected or past history of hypocoagulability or coagulation deficiency conditions
• Known or suspected hemoglobinopathies
• Use of any investigational drug during the current pregnancy
• Known, suspected or past history (last 12 months) of alcohol or drug abuse
• Known hypersensitivity to the active ingredient or to any of its excipients