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

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 Overview

• Status: Completed
• Conditions: Pharmacokinetics
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Nordrhein-Westfalen
    • Mönchengladbach, Nordrhein-Westfalen, Germany, 41061
      • CRS Clinical-Research-Services Mönchengladbach GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 43 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find results for studies related to Bayer products.

Study record dates

Study Major Dates

• Study Start (Actual): May 16, 2017
• Primary Completion (Actual): August 29, 2017
• Study Completion (Actual): October 9, 2017

Study Registration Dates

• First Submitted: May 5, 2017
• First Submitted That Met QC Criteria: May 5, 2017
• First Posted (Actual): May 9, 2017

Study Record Updates

• Last Update Posted (Actual): December 29, 2021
• Last Update Submitted That Met QC Criteria: December 9, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: 18581; 2016-005074-35 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No