Postpartum Hemorrhage
Conditions
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.
Interventions
DRUGCarbetocin
Single infusion of Carbetocin
DRUGPlacebo
Single IV infusion of matching placebo
DRUGPlacebo and Moxifloxacin
Single IV infusion of matching placebo in combination with Single Oral dose of Moxifloxacin
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The trial will consist of two parts; Part A and Part B. Part A is an open-label single group trial while Part B is a double-blind trial with 3 groups.
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Observed Heart rate(HR) values | Up to 240 minutes after Start of Infusion | Part A |
| Change from baseline of HR (∆HR). | 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
| Measure | Time frame | Description |
|---|---|---|
| Vital signs; Pulse rate | Up to follow-up visit (7 to 10 days after the last dose) | 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. |
| Vital signs; Body temperature | Up to follow-up visit (7 to 10 days after the last dose) | 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. |
| Vital signs; Respiratory rate | Up to follow-up visit (7 to 10 days after the last dose) | 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. |
| 12-lead safety ECGs | Up to follow-up visit (7 to 10 days after the last dose) | 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. |
| Clinical chemistry: Changes in Concentration of Blood Urea Nitrogen | 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 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 | 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 Alkaline phosphatase | 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 Aspartate aminotransferase | 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 Creatinine | 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 Alanine aminotransferase | 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 Albumin | 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 Sodium | 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 Potassium | 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 Magnesium | 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 Chloride | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by blood sample collection |
| Hematology: Changes in Concentration of Hemoglobin | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by blood sample collection |
| Hematology: Changes in Concentration of Hematocrit | Up to follow-up visit (7 to 10 days after the last dose) | Part A. 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 |
| Hematology: Changes in Concentration of Red blood cell count | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by blood sample collection |
| Hematology: Changes in Concentration of Platelet 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 | Up to follow-up visit (7 to 10 days after the last dose) | Part A. 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 Protein | 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 | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by urine sample collection |
| Urinalysis parameters: Concentration of Bilirubin | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by urine sample collection |
| Urinalysis parameters: Concentration of Blood | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by urine sample collection |
| Urinalysis parameters: Concentration of Nitrite | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by urine sample collection |
| Urinalysis parameters: Concentration of Urobilinogen | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by urine sample collection |
| Urinalysis parameters: Concentration of Leukocyte esterase | Up to follow-up visit (7 to 10 days after the last dose) | Part A. 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 |
| Treatment-emergent adverse events (TEAEs) | Up to follow-up visit (7 to 10 days after the last dose) | Part A |
| TEAEs | End of Trial (Up to 25 days) | Part B |
| 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 |
| Urinalysis parameters: Concentration of Specific gravity | End of Trial (Up to 25 days) | Part B. Assessed by urine sample collection |
| ∆∆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 |
| Vital signs; Systolic blood pressure and Diastolic blood pressure | Up to follow-up visit (7 to 10 days after the last dose) | 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. |
| Clinical chemistry: Changes in Concentration of Fasting glucose | Up to follow-up visit (7 to 10 days after the last dose) | Part A. Assessed by blood sample collection |
Countries
United States
Outcome results
None listed