Vericiguat is intended to be used for the treatment of cardiovascular diseases, especially heart failure. Heart failure also occurs in children. Therefore, a study testing vericiguat in the treatment of heart failure in paediatric patients is planned under the paediatric investigational plan (PIP). In order to administer vericiguat to children, a vericiguat paediatric formulation is needed. This paediatric formulation is characterized in this study prior to its use in paediatric patients.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
30
Vericiguat high-dose pediatric formulation (fed; American breakfast), 10 mg given as 20 x 0.5 mg mini tablets
Vericiguat high-dose pediatric formulation (fasted),10 mg given as 20 x 0.5 mg mini tablets
Vericiguat low-dose pediatric-formulation (fed; American breakfast), 2.5 mg given as 25 x 0.1 mg mini tablets
CRS Clinical-Research-Services Mönchengladbach GmbH
Mönchengladbach, North Rhine-Westphalia, Germany
Vericiguat area under the plasma concentration vs. time curve divided by dose (AUC/D)
AUC is the area under the curve (mathematically known as definite integral) in a plot of concentration of vericiguat after single dose administration in blood plasma against time (pre-dose until 72 hours after administration). AUC from time 0 to the last data point greater than lower limit of quantification divided by dose (AUC(0-tlast)/D) will be used as primary parameter if AUC cannot be calculated for all profiles, or mean AUC from the last data point to infinity \[AUC(tlast-∞)\] \>20% of AUC. AUC will be analyzed by means of descriptive statistics.
Time frame: 0 - 72 hours
Vericiguat maximum plasma concentration divided by dose (Cmax/D))
Cmax is the maximum observed vericiguat concentration in measured plasma after single dose administration (pre-dose until 72 hours after administration). Cmax/D is the maximum observed drug concentration in measured matrix after single dose administration divided by dose.Cmax will be analyzed by means of descriptive statistics
Time frame: 0 - 72 hours
Number of Adverse Events
As a secondary objective of this study the numbers of AEs will be used to assess safety and tolerability of vericiguat. In a clinical study, an AE is any untoward medical occurrence (i.e. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a patient or clinical investigation subject after providing written informed consent for participation in the study. Therefore, an AE may or may not be temporally or causally associated with the use of a medicinal (investigational) product. Individual listings of AEs will be provided. The incidence of treatment-emergent AEs an drug-related AEs, respectively, will be summarized by treatment using MedDRA terms (highly specific standardised medical terminology).
Time frame: pre-dose until 7 to 14 days after last administration of vericiguat
Palatability of the oro-dispersible tablets and the crushed IR tablets assessed by questionnaire
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10 mg IR tablet, intact (fed; American breakfast)
10 mg IR tablet, crushed (fed; American breakfast)
10 mg IR tablet, intact (fed; Continental breakfast)
As a secondary objective of this study the taste and texture of pediatric formulation (palatability) (mini tablets) and of the crushed IR tablet will be assessed
Time frame: up to 5 minutes after drug administration