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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pharmacokinetics

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male subject Age: 18 to 45 years (inclusive) at informed consent Race: white Body Mass Index (BMI): above or equal 18.0 and below or equal 29.9 kg / m² 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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment A<br>Single oral dose of 20 x 0.5 mg vericiguat high-dose pediatric formulation, fed, American breakfast | Drug: Vericiguat(BAY1021189, high-dose pediatric-formulation)_fed<br>* Vericiguat high-dose pediatric formulation (fed; American breakfast), 10 mg given as 20 x 0.5 mg mini tablets<br>|
| Experimental: Treatment B<br>Single oral dose of 20 x 0.5 mg vericiguat high-dose pediatric formulation, fasted | Drug: Vericiguat(BAY1021189, high-dose pediatric-formulation)_fasted<br>* Vericiguat high-dose pediatric formulation (fasted),10 mg given as 20 x 0.5 mg mini tablets<br>|
| Experimental: Treatment C<br>Single oral dose of 25 x 0.1 mg vericiguat high-dose pediatric formulation, fed, American breakfast | Drug: Vericiguat(BAY1021189, low-dose pediatric-formulation)_fed<br>* Vericiguat low-dose pediatric-formulation (fed; American breakfast), 2.5 mg given as 25 x 0.1 mg mini tablets<br>|
| Active Comparator: Treatment D<br>Single oral dose of 10 mg vericiguat intact IR tablet, adult formulation, fed, American breakfast | Drug: Vericiguat(BAY1021189,10 mg IR film-coated tablets,intact)_fed;American breakfast<br>* 10 mg IR tablet, intact (fed; American breakfast)<br>|
| Experimental: Treatment E<br>Single oral dose of 10 mg vericiguat crushed IR tablet, adult formulation, fed, American breakfast | Drug: Vericiguat(BAY1021189,10 mg IR film-coated tablets,crushed)_fed;American breakfast<br>* 10 mg IR tablet, crushed (fed; American breakfast)<br>|
| Experimental: Treatment F<br>Single oral dose of 10 mg vericiguat intact IR tablet, adult formulation, fed, continental breakfast | Drug: Vericiguat(BAY1021189,10 mg IR film-coated tablets,intact)_fed;Continental breakfast<br>* 10 mg IR tablet, intact (fed; Continental breakfast)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 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 | 0 - 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 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 | 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 | up to 5 minutes after drug administration |