Clinical trial NCT05924321: A Study to Evaluate the Effect of Carbetocin on the QT/QTc Interval in Healthy Subjects
Official title: A Randomized, 2-Part, Crossover Trial to Evaluate the Effect of Carbetocin on the QT/QTc Interval in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Postpartum Hemorrhage
Lead sponsor: Ferring Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2023-06-29
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Observed Heart rate(HR) values
timeFrame: Up to 240 minutes after Start of Infusion
measure: Change from baseline of HR (∆HR).
timeFrame: Up to 240 minutes after Start of Infusion
measure: 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).
timeFrame: Up to 24 hours after Start of Infusion
Secondary outcomes:
measure: Treatment-emergent adverse events (TEAEs)
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Vital signs; Systolic blood pressure and Diastolic blood pressure
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Vital signs; Pulse rate
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Vital signs; Body temperature
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Vital signs; Respiratory rate
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: 12-lead safety ECGs
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Blood Urea Nitrogen
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Bilirubin Total
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Bilirubin direct
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Alkaline phosphatase
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Aspartate aminotransferase
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Alanine aminotransferase
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Albumin
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Sodium
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Potassium
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Magnesium
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Chloride
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Fasting glucose
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Clinical chemistry: Changes in Concentration of Creatinine
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Hematology: Changes in Concentration of Hemoglobin
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Hematology: Changes in Concentration of Hematocrit
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Hematology: Changes in Concentration of Total and differential leukocyte count
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Hematology: Changes in Concentration of Red blood cell count
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Hematology: Changes in Concentration of Platelet count
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of pH
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of specific gravity
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of Protein
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of Glucose
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of Bilirubin
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of Blood
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of Nitrite
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of Urobilinogen
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: Urinalysis parameters: Concentration of Leukocyte esterase
timeFrame: Up to follow-up visit (7 to 10 days after the last dose)
measure: ∆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.
timeFrame: Up to 24 hours after Start of Infusion
measure: 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
timeFrame: Up to 24 hours after Start of Infusion
measure: Categorical outliers for QTcF
timeFrame: Up to 24 hours after Start of Infusion
measure: Categorical outliers for HR
timeFrame: Up to 24 hours after Start of Infusion
measure: Categorical outliers for PR
timeFrame: Up to 24 hours after Start of Infusion
measure: Categorical outliers for QRS
timeFrame: Up to 24 hours after Start of Infusion
measure: Abnormalities in T wave morphology and pathologic U waves, as appropriate.
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: AUClast
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: AUCinf
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: AUC%extrap
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: Cmax
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: Tmax
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: t½
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: MRTinf
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: CL
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: Vss
timeFrame: Up to 24 hours after Start of Infusion
measure: Carbetocin PK parameters: Vz.
timeFrame: Up to 24 hours after Start of Infusion
measure: ∆∆QTc (i.e., ∆∆QTcF or the most appropriate HR correction method) following administration of moxifloxacin.
timeFrame: Up to 24 hours after Start of Infusion
measure: TEAEs
timeFrame: End of Trial (Up to 25 days)
measure: Vital signs; Systolic blood pressure and Diastolic blood pressure
timeFrame: End of Trial (Up to 25 days)
measure: Vital signs; Pulse rate
timeFrame: End of Trial (Up to 25 days)
measure: Vital signs; Body temperature
timeFrame: End of Trial (Up to 25 days)
measure: Vital signs; Respiratory rate
timeFrame: End of Trial (Up to 25 days)
measure: 12-lead safety ECGs
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Blood Urea Nitrogen
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Bilirubin total
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Bilirubin direct
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Alkaline phosphatase
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Aspartate aminotransferase
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Alanine aminotransferase
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Albumin
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Sodium
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Potassium
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Magnesium
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Chloride
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Fasting glucose
timeFrame: End of Trial (Up to 25 days)
measure: Clinical chemistry: Changes in Concentration of Creatinine
timeFrame: End of Trial (Up to 25 days)
measure: Hematology: Changes in Concentration of Hemoglobin
timeFrame: End of Trial (Up to 25 days)
measure: Hematology: Changes in Concentration of Hematocrit
timeFrame: End of Trial (Up to 25 days)
measure: Hematology: Changes in Concentration of Total and Differential leukocyte count
timeFrame: End of Trial (Up to 25 days)
measure: Hematology: Changes in Concentration of Red blood cell count
timeFrame: End of Trial (Up to 25 days)
measure: Hematology: Changes in Concentration of Platelet count
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of pH
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of Specific gravity
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of Protein
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of Glucose
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of Bilirubin
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of Blood
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of Nitrite
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of Urobilinogen
timeFrame: End of Trial (Up to 25 days)
measure: Urinalysis parameters: Concentration of Leukocyte esterase
timeFrame: End of Trial (Up to 25 days)
Other outcomes:
Locations:
city: Tempe
country: United States
facility: Ferring Investigational Site
state: Arizona
Study officials:
affiliation: Ferring Pharmaceuticals
name: Global Clinical Compliance
role: STUDY_DIRECTOR
References: