Sublingual Oxytocin for the Prevention of Post-partum Hemorrhage

Phase 2, Open-label, Randomized, Dose Ascending Trial to Evaluate the Efficacy and Safety of Sublingual Oxytocin for the Prevention of Post-partum Hemorrhage Caused by Uterine Atony in Term Pregnant Women With Uncomplicated Vaginal Delivery

An open-label, randomized, single-center, dose ascending trial will be conducted to evaluate the efficacy and safety of sublingual oxytocin for the prevention of post-partum hemorrhage caused by uterine atony in term pregnant women having an uncomplicated vaginal delivery.

The primary objective is to estimate the optimal effective dose (ED90) of sublingual oxytocin administered during the active management of the third stage of labor to result in satisfactory uterine tone and a cumulative blood loss < 500 ml at 20 minutes after vaginal delivery in 90% of parturients with an acceptable safety profile.

Inclusion Criteria:

1. Women willing and able to provide Informed consent.
2. Women who are able to understand, confirm and give informed consent during an antenatal visit or first stage of labor (cervical dilation <6 cm).
3. Healthy, primiparous or multiparous (2-4 deliveries), term-pregnant female with a gestational age of 37 to 42 weeks (inclusive). Gestational age should be confirmed with an obstetrical ultrasound if available.
4. Aged between 18 and 40 years (both inclusive).
5. Confirmed singleton pregnancy.
6. Based on the Investigator assessment, maternal and fetal conditions are met to expect a vaginal delivery.
7. For participants in the PK subgroup: women with baseline hemoglobin level ≥11 g/dL.

Exclusion Criteria:

1. Women who are unable to provide written Informed consent.
2. Women undergoing an elective or emergency cesarean section.
3. Conditions predisposing to uterine atony and PPH (e.g., previous PPH, placenta praevia, multiple gestation, severe pre-eclampsia, polyhydramnios, uterine fibroids, need for induction of labor, bleeding diathesis, sepsis, body mass index [BMI] ˃ 30 kg/m2 , macrosomia with estimated fetal weight >4500 g, if antenatal ultrasound was performed).
4. Women with moderate or severe anemia (defined as Hb <10 g/dL).
5. Women who have undergone female genital mutilation.
6. Known allergies to carbetocin, other oxytocin homologues or excipients in the medicinal products used in the trial.
7. Oral conditions before administration of sublingual oxytocin such as moderate erythema and edema, severe irritation/inflammation, moderate or severe abrasion.
8. Conditions predisposing to myocardial ischemia due to pre-existing cardiovascular diseases (such as hypertrophic cardiomyopathy, valvular heart disease and/or ischemic heart disease, including vasospasm of the coronary arteries) or known long QT syndrome or related symptoms.
9. Any clinically significant abnormality following review of medical history, laboratory result and physical examination at screening as judged by the Investigator (e.g., severe anemia, antepartum hemorrhage, mental disorder, history of cervical cancer or history of severe infection of the uterus, religious beliefs prohibiting blood transfusions).
10. Previous surgery of the cervix or uterus or any other preexisting condition that could interfere with the measurement of uterine contractility.
11. Current use or use within 30 days before the start of the IMP or reference product of one or more of predefined medications