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.

Study Overview

• Status: Completed
• Conditions: Postpartum Hemorrhage
• Intervention / Treatment: Drug: Carbetocin; Drug: Placebo; Drug: Placebo and Moxifloxacin

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Tempe, Arizona, United States, 85283
      • Ferring Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Carbetocin; Single IV infusion of carbetocin	Drug: Carbetocin; Single infusion of Carbetocin
Placebo Comparator: Placebo; Single IV Infusion of matching placebo	Drug: Placebo; Single IV infusion of matching placebo
Active Comparator: Placebo and Moxifloxacin; Single IV infusion of matching placebo with a single oral dose of moxifloxacin	Drug: Placebo and Moxifloxacin; Single IV infusion of matching placebo in combination with Single Oral dose of Moxifloxacin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Observed Heart rate(HR) values	Part A	Up to 240 minutes after Start of Infusion
Change from baseline of HR (∆HR).	Part A	Up to 240 minutes after Start of Infusion
Placebo-corrected change from baseline in QT interval (∆∆QTc) using the most appropriate HR correction method (i.e., ∆∆QTcF if Fridericia's method is used).	Part B	Up to 24 hours after Start of Infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events (TEAEs)	Part A	Up to follow-up visit (7 to 10 days after the last dose)
Vital signs; Systolic blood pressure and Diastolic blood pressure	Part A. The parameters which are measured are Systolic blood pressure and Diastolic blood pressure. Each vital sign parameter value is classified as either Low, Normal or High. Summary tables will be prepared by treatment displaying the number and percentage of subjects with normal pre-administration values who had at least one markedly abnormal post-administration values.	Up to follow-up visit (7 to 10 days after the last dose)
Vital signs; Pulse rate	Part A. The parameter which is measured is Pulse rate. The vital sign parameter value is classified as either Low, Normal or High. Summary tables will be prepared by treatment displaying the number and percentage of subjects with normal pre-administration values who had at least one markedly abnormal post-administration values.	Up to follow-up visit (7 to 10 days after the last dose)
Vital signs; Body temperature	Part A. The parameter which is measured is Body temperature. The vital sign parameter value is classified as either Low, Normal or High. Summary tables will be prepared by treatment displaying the number and percentage of subjects with normal pre-administration values who had at least one markedly abnormal post-administration values.	Up to follow-up visit (7 to 10 days after the last dose)
Vital signs; Respiratory rate	Part A. The parameter which is measured is Respiratory rate. The vital sign parameter value is classified as either Low, Normal or High. Summary tables will be prepared by treatment displaying the number and percentage of subjects with normal pre-administration values who had at least one markedly abnormal post-administration values.	Up to follow-up visit (7 to 10 days after the last dose)
12-lead safety ECGs	Part A. The parameters which are measured are QT, QTc, QTcF, QRS, PR, RR and HR. Subjects' maximum change from baseline and subject's maximum post-baseline values in ECG parameters will be categorized and the number and percentage of subjects in each group will be summarized. The results will be interpreted as "normal", "abnormal, not clinically significant" or "abnormal clinically significant", and the interpretation will be summarized for each treatment and scheduled time point using frequency counts and percentages.	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Blood Urea Nitrogen	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Bilirubin Total	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Bilirubin direct	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Alkaline phosphatase	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Aspartate aminotransferase	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Alanine aminotransferase	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Albumin	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Sodium	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Potassium	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Magnesium	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Chloride	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Fasting glucose	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Clinical chemistry: Changes in Concentration of Creatinine	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Hematology: Changes in Concentration of Hemoglobin	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Hematology: Changes in Concentration of Hematocrit	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Hematology: Changes in Concentration of Total and differential leukocyte count	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Hematology: Changes in Concentration of Red blood cell count	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Hematology: Changes in Concentration of Platelet count	Part A. Assessed by blood sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of pH	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of specific gravity	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of Protein	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of Glucose	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of Bilirubin	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of Blood	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of Nitrite	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of Urobilinogen	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
Urinalysis parameters: Concentration of Leukocyte esterase	Part A. Assessed by urine sample collection	Up to follow-up visit (7 to 10 days after the last dose)
∆HR, PR change from baseline (∆PR), RR change from baseline (∆RR), QRS change from baseline (∆QRS), and QTcF change from baseline (∆QTcF), if not selected as the primary endpoint.	Part B	Up to 24 hours after Start of Infusion
Placebo-corrected ∆HR (∆∆HR), placebo-corrected ∆PR (∆∆PR), placebo-corrected ∆RR (∆∆RR), placebo-corrected ∆QRS (∆∆QRS), and ∆∆QTcF, if not selected as the primary endpoint	Part B	Up to 24 hours after Start of Infusion
Categorical outliers for QTcF	Part B	Up to 24 hours after Start of Infusion
Categorical outliers for HR	Part B	Up to 24 hours after Start of Infusion
Categorical outliers for PR	Part B	Up to 24 hours after Start of Infusion
Categorical outliers for QRS	Part B	Up to 24 hours after Start of Infusion
Abnormalities in T wave morphology and pathologic U waves, as appropriate.	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: AUClast	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: AUCinf	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: AUC%extrap	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: Cmax	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: Tmax	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: t½	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: MRTinf	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: CL	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: Vss	Part B	Up to 24 hours after Start of Infusion
Carbetocin PK parameters: Vz.	Part B	Up to 24 hours after Start of Infusion
∆∆QTc (i.e., ∆∆QTcF or the most appropriate HR correction method) following administration of moxifloxacin.	Part B	Up to 24 hours after Start of Infusion
TEAEs	Part B	End of Trial (Up to 25 days)
Vital signs; Systolic blood pressure and Diastolic blood pressure	Part B. The parameters which are measured are Systolic blood pressure and Diastolic blood pressure. Each vital sign parameter value is classified as either Low, Normal or High	End of Trial (Up to 25 days)
Vital signs; Pulse rate	Part B. The parameter which is measured is Pulse rate. The sign parameter value is classified as either Low, Normal or High	End of Trial (Up to 25 days)
Vital signs; Body temperature	Part B. The parameter which is measured is Body temperature. The sign parameter value is classified as either Low, Normal or High	End of Trial (Up to 25 days)
Vital signs; Respiratory rate	Part B. The parameter which is measured is Respiratory rate. The sign parameter value is classified as either Low, Normal or High	End of Trial (Up to 25 days)
12-lead safety ECGs	Part B. The parameters which are measured are QT, QTc, QTcF, QRS, PR, RR and HR. The results will be interpreted as "normal", "abnormal, not clinically significant" or "abnormal clinically significant".	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Blood Urea Nitrogen	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Bilirubin total	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Bilirubin direct	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Alkaline phosphatase	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Aspartate aminotransferase	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Alanine aminotransferase	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Albumin	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Sodium	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Potassium	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Magnesium	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Chloride	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Fasting glucose	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Clinical chemistry: Changes in Concentration of Creatinine	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Hematology: Changes in Concentration of Hemoglobin	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Hematology: Changes in Concentration of Hematocrit	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Hematology: Changes in Concentration of Total and Differential leukocyte count	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Hematology: Changes in Concentration of Red blood cell count	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Hematology: Changes in Concentration of Platelet count	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of pH	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of Specific gravity	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of Protein	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of Glucose	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of Bilirubin	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of Blood	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of Nitrite	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of Urobilinogen	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Urinalysis parameters: Concentration of Leukocyte esterase	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)

Collaborators and Investigators

• Sponsor: Ferring Pharmaceuticals
• Investigators: Study Director: Global Clinical Compliance, Ferring Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2023
• Primary Completion (Actual): September 21, 2023
• Study Completion (Actual): September 21, 2023

Study Registration Dates

• First Submitted: May 3, 2023
• First Submitted That Met QC Criteria: June 20, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): September 3, 2024
• Last Update Submitted That Met QC Criteria: August 29, 2024
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Pregnancy Complications; Obstetric Labor Complications; Puerperal Disorders; Uterine Hemorrhage; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Hemorrhage; Postpartum Hemorrhage; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antineoplastic Agents; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Anti-Bacterial Agents; Reproductive Control Agents; Oxytocics; Moxifloxacin; Carbetocin
• Other Study ID Numbers: 000421

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No