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

A Randomised, Double-blind, Parallel Group, Dose-ranging, Placebo-controlled, Multi-centre, Proof of Concept Study Assessing the Effect of Four Different Single Bolus Intravenous Doses of FE200440 (0.3, 1, 3, 10 mg) and Placebo on Stopping Preterm Labour and Uterine Contractions in Pregnant Women With Advanced Gestational Age

• 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 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:

1. Signed Informed Consent Form, prior to screening evaluations
2. Mother and fetus in good general health
3. Pregnant women age ≥ 18 years
4. 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)
5. At randomisation, there must be 6 or more uterine contractions of at least 30 seconds duration during a 30 minutes interval
6. At randomisation, the cervical length must be ≤ 15 mm (by transvaginal ultrasound)
7. At randomisation, the cervical dilatation must be >1 cm and <4 cm (by vaginal examination

Exclusion Criteria:

1. 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)

2. Controlled or uncontrolled diabetes mellitus (pre-gestational or gestational)

3. Eclampsia or severe preeclampsia in the current pregnancy

4. Previous major uterine surgery (e.g. myomectomy for leiomyomas), congenital uterine abnormalities, large leiomyomas, or retained intrauterine device

5. Rupture of membrane in the current pregnancy

6. Placenta praevia in the current pregnancy

7. a)

8. Oligohydramnios or polyhydramnios in the current pregnancy defined as amniotic fluid index (AFI) below 7.2 cm or above 27.8 cm

9. Fetal weight (based on ultrasound) outside the ± 2SD limits provided in Appendix B

10. Use of cervical cerclage in the current pregnancy

11. Current multiple pregnancy

12. Fetal death in utero in previous or current pregnancy

13. Fetus with known or suspected abnormal karyotype or major malformations in the current pregnancy

14. Abnormal fetal heart rate which the Investigator judges to reflect fetal distress

15. 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

16. Treatment with anticoagulation or fibrinolytic therapies prior to screening, or known or suspected or past history of thromboembolic disorders

17. Known, suspected or past history of hypocoagulability or coagulation deficiency conditions

18. Known or suspected hemoglobinopathies

19. Use of any investigational drug during the current pregnancy

20. Known, suspected or past history (last 12 months) of alcohol or drug abuse

21. Known hypersensitivity to the active ingredient or to any of its excipients