A Study to Evaluate the Effect of Carbetocin on the QT/QTc Interval in Healthy Subjects

A Randomized, 2-Part, Crossover Trial to Evaluate the Effect of Carbetocin on the QT/QTc Interval in Healthy Subjects

Carbetocin is an oxytocin receptor agonist that selectively binds to receptors in the smooth muscle of the uterus, stimulates rhythmic contractions of the uterus, increases the frequency of existing contractions, and raises the tone of the uterine musculature. Carbetocin is approved in >100 countries for the prevention of postpartum hemorrhage due to uterine atony in women following cesarean or vaginal delivery. Per regulatory requirements, the current trial will evaluate the effects of high clinical exposure of carbetocin on the QT interval corrected for heart rate (QTc) as measured by ECG in healthy men and women.

Inclusion Criteria:

• Healthy, adult, male or female subjects, 18-45 years of age, inclusive, at the screening visit.
• Body mass index (BMI) ≥ 18.5 and ≤29.9 kg/m2 at the screening visit.
• Continuous non-smoker who has not used nicotine- or tobacco-containing products for at least 3 months prior to first dosing.

Exclusion Criteria:

• Sustained supine systolic blood pressure ≥130 mmHg or <90 mmHg, supine diastolic blood pressure ≥80 mmHg or <50 mmHg at screening or first check-in.

• History or presence of clinically significant ECG findings in the opinion of the Principal Investigator (PI) or designee at the screening visit or first check-in, including each of the following:

  • HR <45 bpm or >100 bpm.
  • QTcF is ≥450 msec (males) or ≥460 msec (females).
  • QRS ≥110 msec; if ≥110 msec, result will be confirmed by a manual over read.
  • PR ≥200 msec.

• History or presence of:

  • Risk factors for Torsades de Pointes (e.g., heart failure, cardiomyopathy, family history of Long QT syndrome, Brugada syndrome, or sudden cardiac death).
  • Sick sinus syndrome, second- or third-degree atrioventricular block, myocardial infarction, angina, pulmonary congestion, symptomatic or significant cardiac arrhythmia, or clinically significant conduction abnormalities.
  • Clinically significant abnormal laboratory assessments including hypokalemia, hypercalcemia, or hypomagnesemia, in the opinion of the PI or designee.