Relative Bioavailability and Food Effect Study With Vericiguat to Characterize the Pediatric Formulation in Adult Healthy Subjects

Phase 1

Completed

Interventions: Drug: Vericiguat(BAY1021189, low-dose pediatric-formulation)_fed
Drug: Vericiguat(BAY1021189,10 mg IR film-coated tablets,intact)_fed;American breakfast
Drug: Vericiguat(BAY1021189,10 mg IR film-coated tablets,intact)_fed;Continental breakfast
Drug: Vericiguat(BAY1021189, high-dose pediatric-formulation)_fed
Drug: Vericiguat(BAY1021189, high-dose pediatric-formulation)_fasted
Drug: Vericiguat(BAY1021189,10 mg IR film-coated tablets,crushed)_fed;American breakfast

Brief Summary: 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.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
Known hypersensitivity to the study drugs (active substances or excipients of the preparations)
Known severe allergies, non-allergic drug reactions, or multiple drug allergies
Febrile illness within 1 week prior to the first study drug administration
History of postural syncopes
A history of relevant diseases of vital organs, of the central nervous system or other organs
A history of relevant smell and / or taste disorders
Relevant diseases within the last 4 weeks prior to the first study drug administration
Medical disorder that would impair the subject's ability to complete the study in the opinion of the investigator.
Known gastro-intestinal disorders (e.g. stomach ulcers, duodenal ulcers, gastrointestinal bleeding) or inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)

Arm && Interventions

Group	Intervention	Description
Treatment C	Vericiguat(BAY1021189, low-dose pediatric-formulation)_fed	Single oral dose of 25 x 0.1 mg vericiguat high-dose pediatric formulation, fed, American breakfast
Treatment D	Vericiguat(BAY1021189,10 mg IR film-coated tablets,intact)_fed;American breakfast	Single oral dose of 10 mg vericiguat intact IR tablet, adult formulation, fed, American breakfast
Treatment F	Vericiguat(BAY1021189,10 mg IR film-coated tablets,intact)_fed;Continental breakfast	Single oral dose of 10 mg vericiguat intact IR tablet, adult formulation, fed, continental breakfast
Treatment A	Vericiguat(BAY1021189, high-dose pediatric-formulation)_fed	Single oral dose of 20 x 0.5 mg vericiguat high-dose pediatric formulation, fed, American breakfast
Treatment B	Vericiguat(BAY1021189, high-dose pediatric-formulation)_fasted	Single oral dose of 20 x 0.5 mg vericiguat high-dose pediatric formulation, fasted
Treatment E	Vericiguat(BAY1021189,10 mg IR film-coated tablets,crushed)_fed;American breakfast	Single oral dose of 10 mg vericiguat crushed IR tablet, adult formulation, fed, American breakfast

Primary Outcome Measures

Name	Time	Method
Vericiguat area under the plasma concentration vs. time curve divided by dose (AUC/D)	0 - 72 hours	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.
Vericiguat maximum plasma concentration divided by dose (Cmax/D))	0 - 72 hours	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

Secondary Outcome Measures

Name	Time	Method
Number of Adverse Events	pre-dose until 7 to 14 days after last administration of vericiguat	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).
Palatability of the oro-dispersible tablets and the crushed IR tablets assessed by questionnaire	up to 5 minutes after drug administration	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

Locations (1): CRS Clinical-Research-Services Mönchengladbach GmbH
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Mönchengladbach, Nordrhein-Westfalen, Germany