A Study to Evaluate the Effect of Carbetocin on the QT/QTc Interval in Healthy Subjects
- Conditions
- Postpartum Hemorrhage
- Interventions
- Registration Number
- NCT05924321
- Lead Sponsor
- Ferring Pharmaceuticals
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 40
- 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.
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo Placebo Single IV Infusion of matching placebo Placebo and Moxifloxacin Placebo and Moxifloxacin Single IV infusion of matching placebo with a single oral dose of moxifloxacin Carbetocin Carbetocin Single IV infusion of carbetocin
- Primary Outcome Measures
Name Time Method Change from baseline of HR (∆HR). Up to 240 minutes after Start of Infusion Part A
Observed Heart rate(HR) values Up to 240 minutes after Start of Infusion Part A
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). Up to 24 hours after Start of Infusion Part B
- Secondary Outcome Measures
Name Time Method Treatment-emergent adverse events (TEAEs) Up to follow-up visit (7 to 10 days after the last dose) Part A
Vital signs; Pulse rate End of Trial (Up to 25 days) Part B. The parameter which is measured is Pulse rate. The sign parameter value is classified as either Low, Normal or High
Vital signs; Body temperature End of Trial (Up to 25 days) Part B. The parameter which is measured is Body temperature. The sign parameter value is classified as either Low, Normal or High
Vital signs; Respiratory rate End of Trial (Up to 25 days) Part B. The parameter which is measured is Respiratory rate. The sign parameter value is classified as either Low, Normal or High
Vital signs; Systolic blood pressure and Diastolic blood pressure End of Trial (Up to 25 days) 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 High12-lead safety ECGs End of Trial (Up to 25 days) 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".
Clinical chemistry: Changes in Concentration of Blood Urea Nitrogen End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Bilirubin Total Up to follow-up visit (7 to 10 days after the last dose) Part A. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Bilirubin direct End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Alkaline phosphatase End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Aspartate aminotransferase End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Alanine aminotransferase End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Albumin End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Sodium End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Potassium End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Urinalysis parameters: Concentration of Protein End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
Clinical chemistry: Changes in Concentration of Magnesium End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Chloride End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Fasting glucose End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Clinical chemistry: Changes in Concentration of Creatinine End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Hematology: Changes in Concentration of Red blood cell count End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Hematology: Changes in Concentration of Platelet count End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Hematology: Changes in Concentration of Hemoglobin End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Hematology: Changes in Concentration of Hematocrit End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Hematology: Changes in Concentration of Total and differential leukocyte count Up to follow-up visit (7 to 10 days after the last dose) Part A. Assessed by blood sample collection
Urinalysis parameters: Concentration of pH End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
Urinalysis parameters: Concentration of specific gravity Up to follow-up visit (7 to 10 days after the last dose) Part A. Assessed by urine sample collection
Urinalysis parameters: Concentration of Glucose End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
Urinalysis parameters: Concentration of Bilirubin End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
Urinalysis parameters: Concentration of Blood End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
Urinalysis parameters: Concentration of Nitrite End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
Urinalysis parameters: Concentration of Urobilinogen End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
Urinalysis parameters: Concentration of Leukocyte esterase End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
∆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. Up to 24 hours after Start of Infusion Part B
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 Up to 24 hours after Start of Infusion Part B
Categorical outliers for QTcF Up to 24 hours after Start of Infusion Part B
Categorical outliers for HR Up to 24 hours after Start of Infusion Part B
Categorical outliers for PR Up to 24 hours after Start of Infusion Part B
Categorical outliers for QRS Up to 24 hours after Start of Infusion Part B
Abnormalities in T wave morphology and pathologic U waves, as appropriate. Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: AUClast Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: AUCinf Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: AUC%extrap Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: Cmax Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: Tmax Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: t½ Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: MRTinf Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: CL Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: Vss Up to 24 hours after Start of Infusion Part B
Carbetocin PK parameters: Vz. Up to 24 hours after Start of Infusion Part B
∆∆QTc (i.e., ∆∆QTcF or the most appropriate HR correction method) following administration of moxifloxacin. Up to 24 hours after Start of Infusion Part B
TEAEs End of Trial (Up to 25 days) Part B
Urinalysis parameters: Concentration of Specific gravity End of Trial (Up to 25 days) Part B. Assessed by urine sample collection
Clinical chemistry: Changes in Concentration of Bilirubin total End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Hematology: Changes in Concentration of Total and Differential leukocyte count End of Trial (Up to 25 days) Part B. Assessed by blood sample collection
Trial Locations
- Locations (1)
Ferring Investigational Site
🇺🇸Tempe, Arizona, United States