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

Postpartum Hemorrhage Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05924321
• Other study ID #: 000421
• Status: Completed
• Phase: Phase 1
• Start date: May 25, 2023
• Est. completion date: September 21, 2023

Study information

• Verified date: May 2023
• Source: Ferring Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: September 21, 2023
• Est. primary completion date: September 21, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hemorrhage
• Postpartum Hemorrhage

Intervention

Drug:
• Carbetocin
Single infusion of Carbetocin
• Placebo
Single IV infusion of matching placebo
• Placebo and Moxifloxacin
Single IV infusion of matching placebo in combination with Single Oral dose of Moxifloxacin

Locations

Country	Name	City	State
United States	Ferring Investigational Site	Tempe	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Ferring Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Observed Heart rate(HR) values	Part A	Up to 240 minutes after Start of Infusion
Primary	Change from baseline of HR (?HR).	Part A	Up to 240 minutes after Start of Infusion
Primary	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	Treatment-emergent adverse events (TEAEs)	Part A	Up to follow-up visit (7 to 10 days after the last dose)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	?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
Secondary	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
Secondary	Categorical outliers for QTcF	Part B	Up to 24 hours after Start of Infusion
Secondary	Categorical outliers for HR	Part B	Up to 24 hours after Start of Infusion
Secondary	Categorical outliers for PR	Part B	Up to 24 hours after Start of Infusion
Secondary	Categorical outliers for QRS	Part B	Up to 24 hours after Start of Infusion
Secondary	Abnormalities in T wave morphology and pathologic U waves, as appropriate.	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: AUClast	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: AUCinf	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: AUC%extrap	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: Cmax	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: Tmax	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: t½	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: MRTinf	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: CL	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: Vss	Part B	Up to 24 hours after Start of Infusion
Secondary	Carbetocin PK parameters: Vz.	Part B	Up to 24 hours after Start of Infusion
Secondary	??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
Secondary	TEAEs	Part B	End of Trial (Up to 25 days)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Clinical chemistry: Changes in Concentration of Blood Urea Nitrogen	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Bilirubin total	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Bilirubin direct	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Alkaline phosphatase	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Aspartate aminotransferase	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Alanine aminotransferase	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Albumin	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Sodium	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Potassium	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Magnesium	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Chloride	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Fasting glucose	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Clinical chemistry: Changes in Concentration of Creatinine	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Hematology: Changes in Concentration of Hemoglobin	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Hematology: Changes in Concentration of Hematocrit	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Hematology: Changes in Concentration of Total and Differential leukocyte count	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Hematology: Changes in Concentration of Red blood cell count	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Hematology: Changes in Concentration of Platelet count	Part B. Assessed by blood sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of pH	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of Specific gravity	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of Protein	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of Glucose	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of Bilirubin	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of Blood	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of Nitrite	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of Urobilinogen	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)
Secondary	Urinalysis parameters: Concentration of Leukocyte esterase	Part B. Assessed by urine sample collection	End of Trial (Up to 25 days)