Pivotal Relative Bioavailability Study to Investigate the Pharmacokinetics and Food Effect of Single Oral Doses of Vericiguat Given as Pediatric Oral Suspension Formulations in Comparison to the 10 mg IR Tablet in Healthy Male Participants in a Randomized, Open-label, 4-fold Crossover Design
Overview
- Phase
- Phase 1
- Intervention
- Vericiguat (BAY1021189) - Intervention A
- Conditions
- Heart Failure
- Sponsor
- Bayer
- Enrollment
- 36
- Locations
- 1
- Primary Endpoint
- AUC(0-tlast) of vericiguat (a single oral dose of the pediatric high concentration formulation in comparison to vericiguat intact tablet in fed condition)
- Status
- Completed
- Last Updated
- 3 years ago
Overview
Brief Summary
Researchers are looking for a better way to treat heart failure, a condition in which the heart does not pump blood as well as it should. Heart failure can happen in both adults and children.
The study treatment, vericiguat, is already available for doctors to give to adults who have heart failure. It works by increasing the activity of an enzyme called soluble guanylate cyclase (sGC). The sGC enzyme helps regulate the heart and blood circulation.
The current form of vericiguat is a tablet that releases the "active substance" immediately. The "active substance" is the part of the drug that works in the body to treat the condition. Vericiguat is currently only available as a treatment for adults. Researchers think vericiguat could help treat children with heart failure, but think it will be easiest for them to take a liquid treatment.
Another study is planned to find out how well vericiguat works in children who have a specific type of heart failure. Before researchers can give vericiguat to children, they must first study different doses and ways of taking vericiguat in adults. In this study, the researchers will study a new liquid form of vericiguat in adults. This form is also known as the "pediatric formulation".
In this study, the researchers want to find out how the new pediatric formulation of vericiguat moves into, through, and out of the body compared to the currently approved tablet form for adults. The researchers also want to find out if eating food affects the new pediatric formulation differently than the current tablet form of vericiguat.
The study will include about 36 healthy white male participants aged between 18 and 45 years old.
During this study, the participants will all take 4 different treatments in different orders. They will take:
- a high dose of vericiguat in the new pediatric formulation, with food
- a high dose of vericiguat in the new pediatric formulation, without food
- a low dose of vericiguat in the new pediatric formulation, with food
- a dose of the currently available tablet form, with food While taking each study treatment, the participants will stay at the study site for 4 days. There will be a break of at least 10 days between each treatment. Overall, the participants will be in this study for about 11 weeks.
During the study, the participants will:
- have blood and urine samples taken
- have their overall health and heart health checked
- answer questions about how the new pediatric formulation tastes
- answer questions about any adverse events they are having An adverse event is any medical problem that a participant has during a study. Doctors keep track of all adverse events that happen in studies, even if they do not think the adverse events might be related to the study treatments.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Healthy male subjects
- •Age 18 -45 years
- •Body Mass Index (BMI): above or equal 18.5 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
- •Febrile illness (temperature ≥38.0 oC) within 4 weeks prior to admission to the ward
- •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 intervention administration
- •Known gastro-intestinal disorders (e.g. stomach ulcers, duodenal ulcers, gastro-intestinal bleeding) or inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis)
- •Regular use of medicines in the 4 weeks prior to first dosing
- •Regular use of therapeutic or recreational drugs (e.g. carnitine products, anabolics, high-dose vitamins)
- •Use of medication (prescription or over the counter) or herbal products within 2 weeks before first study intervention administration which could oppose the study objectives or which might influence them
- •Criteria which in the opinion of the investigator preclude participation for scientific reasons, for reasons of compliance, or for reasons of the participant's safety
Arms & Interventions
B-A-D-C
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention A
B-A-D-C
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention B
B-A-D-C
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention C
B-A-D-C
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (Verquvo, BAY1021189) - Intervention D
C-D-A-B
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention A
C-D-A-B
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention B
C-D-A-B
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention C
C-D-A-B
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (Verquvo, BAY1021189) - Intervention D
D-B-C-A
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention A
D-B-C-A
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention B
D-B-C-A
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention C
D-B-C-A
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (Verquvo, BAY1021189) - Intervention D
A-C-B-D
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention A
A-C-B-D
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention B
A-C-B-D
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (BAY1021189) - Intervention C
A-C-B-D
4-fold crossover design with 4 interventions, 4 intervention periods, and 4 intervention sequences. (according to Williams design \[balanced for 1-period-carry-over\]).
Intervention: Vericiguat (Verquvo, BAY1021189) - Intervention D
Outcomes
Primary Outcomes
AUC(0-tlast) of vericiguat (a single oral dose of the pediatric high concentration formulation in comparison to vericiguat intact tablet in fed condition)
Time Frame: From pre-dose until 72 hours after dosing in each intervention period
AUC(0-tlast): AUC from time 0 to the last data point \> lower limit of quantitation (LLOQ)
AUC of vericiguat (a single oral dose of the pediatric high concentration formulation in comparison to vericiguat intact tablet in fed condition)
Time Frame: From pre-dose until 72 hours after dosing in each intervention period
AUC: area under the concentration vs. time curve from zero to infinity after single (first) dose, calculated up by linear trapezoidal rule, down by logarithmic trapezoidal rule
Cmax of vericiguat (a single oral dose of the pediatric high concentration formulation in comparison to vericiguat intact tablet in fed condition)
Time Frame: From pre-dose until 72 hours after dosing in each intervention period
Cmax: maximum observed drug concentration in measured matrix after single dose administration
Secondary Outcomes
- AUC(0-tlast)/D of vericiguat ( a single oral dose of 2.5 mg of the pediatric low-concentration formulation in comparison to 10 mg vericiguat intact tablet in fed condition)(From pre-dose until 72 hours after dosing in each intervention period)
- AUC/D of vericiguat (a single oral dose of 10 mg of the pediatric high-concentration formulation in comparison to a single oral dose of 2.5 mg of the pediatric low-concentration formulation in fed condition)(From pre-dose until 72 hours after dosing in each intervention period)
- Cmax/D of vericiguat (a single oral dose of 10 mg of the pediatric high-concentration formulation in comparison to a single oral dose of 2.5 mg of the pediatric low-concentration formulation in fed condition)(From pre-dose until 72 hours after dosing in each intervention period)
- AUC/D of vericiguat ( a single oral dose of 2.5 mg of the pediatric low-concentration formulation in comparison to 10 mg vericiguat intact tablet in fed condition)(From pre-dose until 72 hours after dosing in each intervention period)
- Cmax/D of vericiguat ( a single oral dose of 2.5 mg of the pediatric low-concentration formulation in comparison to 10 mg vericiguat intact tablet in fed condition)(From pre-dose until 72 hours after dosing in each intervention period)
- AUC(0-tlast)/D of vericiguat (a single oral dose of 10 mg of the pediatric high-concentration formulation in comparison to a single oral dose of 2.5 mg of the pediatric low-concentration formulation in fed condition)(From pre-dose until 72 hours after dosing in each intervention period)
- Number of participants with treatment emergent adverse events (TEAEs)(From dosing to 5 days after each dose per period (estimate duration is 20 days))
- Questionnaire by means of descriptive statistics(0 - 30 minutes)
- Cmax of vericiguat (a high fat, high calorie meal on the PK of vericiguat after a single oral dose of high-concentration pediatric formulation in comparison to the fasted state)(From pre-dose until 72 hours after dosing in each intervention period)
- AUC of vericiguat (a high fat, high calorie meal on the PK of vericiguat after a single oral dose of high-concentration pediatric formulation in comparison to the fasted state)(From pre-dose until 72 hours after dosing in each intervention period)
- AUC(0-tlast) of vericiguat (a high fat, high calorie meal on the PK of vericiguat after a single oral dose of high-concentration pediatric formulation in comparison to the fasted state)(From pre-dose until 72 hours after dosing in each intervention period)