Trial Condition(s):
Clinical Pharmacology
Multiple Dose escalation Phase I study of BAY1021189
Bayer Identifier:
15357
ClinicalTrials.gov Identifier:
Not Available
EudraCT Number:
EU CT Number:
Not Available
Study Completed
Trial Purpose
The primary objective of this study was to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of once daily 1.25, 5.0 and 10 mg and twice daily 5 mg of vericiguat administered orally as one or multiples of 1.25 mg IR-tablets over 7 days in 12 healthy male subjects (9 on active drug and 3 on placebo) per dose step.
Inclusion Criteria
- Healthy male subject - Age: 18 to 45 years (inclusive) at the first screening visit - Ethnicity: white - Body mass index (BMI): above/equal 18 and below/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 drug (active substances or excipients of the preparations) - Known severe allergies, non-allergic drug reactions, or multiple drug allergies - Relevant diseases within the last 4 weeks prior to study drug administration - Febrile illness within 1 week before study drug administration - History of postural syncopes - Regular use of medicines - Regular use of therapeutic or recreational drugs - Use of medication within 2 weeks before study drug administration which could oppose the study objectives or which might influence them
Trial Summary
Enrollment Goal
46
Trial Dates
Phase
1
Could I receive a placebo?
No
Products
Verquvo (Vericiguat, BAY1021189)
Accepts Healthy Volunteers
Yes
Where to Participate
Loading...
Locations
Status
| Locations | Status | |
|---|---|---|
Locations Investigative Site Wuppertal, Germany, 42113 | Status Completed | Contact Us: E-mail: [email protected] Phone: Not Available |
Trial Design
Multiple dose escalation study to investigate safety, tolerability, pharmacokinetics and pharmacodynamics of BAY 1021189 after oral dosing of 1.25, 5, 10 mg OD and 5 mg BID over 7 days given as 1.25 mg or multiples of 1.25 mg IR-tablet in 12 healthy male subjects per dose step in a randomized, single-blind, placebo-controlled, group-comparison design
Trial Type:
Interventional
Intervention Type:
Drug
Trial Purpose:
Basic Science
Allocation:
Randomized
Blinding:
N/A
Assignment:
N/A
Trial Arms:
5
Primary Outcome
- Area Under the Plasma Concentration Versus Time Curve From Zero to Last Data Point (AUC[0tlast]) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Maximum Drug Plasma Concentration (Cmax) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Area Under the Plasma Concentration Versus Time Curve During any Dosing Interval After Multiple Doses (AUCtau,md) of Vericiguat in Plasma on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Maximum Drug Plasma Concentration During any Dosing Interval After Multiple Doses (Cmax,md) of Vericiguat on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Number of Subjects With Clinically Relevant Changes in Blood Pressure After Vericiguat Treatment in Comparison to PlaceboTimeframe: Baseline up to follow-up visit (10 days after last dose)
- Change From Baseline in Heart Rate Over 1 Minute at Days 1 and 7Timeframe: Baseline, Day 1 (start of Day 2) and Day 7 (start of Day 8)
- Change From Baseline in Impedance Cardiographic Assessments at Days 1 and 7: Cardiac OutputTimeframe: Baseline, Day 1 (start of Day 2) and Day 7 (start of Day 8)
- Change From Baseline in Impedance Cardiographic Assessments at Days 1 and 7: Cardiac IndexTimeframe: Baseline, Day 1 (start of Day 2) and Day 7 (start of Day 8)
- Change From Baseline in Impedance Cardiographic Assessments at Days 1 and 7: Heart RateTimeframe: Baseline, Day 1 (start of Day 2) and Day 7 (start of Day 8)
- Change From Baseline in Impedance Cardiographic Assessments at Days 1 and 7: Stroke VolumeTimeframe: Baseline, Day 1 (start of Day 2) and Day 7 (start of Day 8)
- Change From Baseline in Impedance Cardiographic Assessments at Days 1 and 7: Systemic Vascular ResistanceTimeframe: Baseline, Day 1 (start of Day 2) and Day 7 (start of Day 8)
- Change From Baseline in Plasma Cyclic Guanosine Monophosphate (cGMP) at Days 1 and 7Timeframe: Baseline, Day 1 (start of Day 2: 0, 12 h), Day 7 (start of Day 8: 0, 12 h)
- Number of Subjects With Treatment-emergent Adverse Events (TEAEs)Timeframe: Baseline up to follow-up visit (10 days after last dose)
- Number of Subjects With Abnormal Clinical Laboratory FindingsTimeframe: Baseline up to follow-up visit (10 days after last dose)
- Number of Subjects With Clinically Relevant Findings in Electrocardiogram (ECG) ParametersTimeframe: Baseline up to follow-up visit (10 days after last dose)
Secondary Outcome
- Area Under the Plasma Concentration Versus Time Curve From Zero to Last Data Point Divided by Dose (AUC[0tlast]/ D) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Area Under the Plasma Concentration Versus Time Curve From Zero to Last Data Point Divided by Dose per Kilogram Body Weight (AUC[0tlast] norm) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Maximum Drug Plasma Concentration Divided by Dose (Cmax/D) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Maximum Drug Plasma Concentration Divided by Dose per Kilogram Body Weight (Cmax,norm) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Half-life Associated With the Terminal Slope (t1/2) of Vericiguat in Plasma on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Time to Reach Maximum Drug Plasma Concentration (tmax) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Mean Residence Time (MRT) of Vericiguat in Plasma on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Amount of Drug Excreted via Urine (AE,ur[t1t2]) of Vericiguat on Day 1Timeframe: 0-48 h
- Renal Clearance (CLR) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Total Body Clearance of Drug from Plasma (CL/F) of Vericiguat on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Apparent Volume of Distribution During Terminal Phase (Vz/F) of Vericiguat in Plasma on Day 1Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 1
- Ratio of Maximum Drug Concentration to Concentration at 24 Hours (Cmax/C24) for Once Daily Vericiguat Treatment on Day 1Timeframe: 0-24 h on Day 1
- Ratio of Maximum Drug Concentration to Concentration at 12 Hours (Cmax/C12) for Twice Daily Vericiguat Treatment on Day 1Timeframe: 0-12 h on Day 1
- AUC During any Dosing Interval After Multiple Doses Divided by Dose (AUCtau,md/D) of Vericiguat in Plasma on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- AUC During any Dosing Interval After Multiple Dose per Kilogram Body Weight (AUCtau,md,norm) of Vericiguat in Plasma on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Maximum Drug Plasma Concentration During any Dosing Interval After Multiple Doses Divided by Dose (Cmax,md/D) of Vericiguat on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Maximum Drug Plasma Concentration During any Dosing Interval After Multiple Doses per Kilogram Body Weight (Cmax,md,norm) of Vericiguat on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Time to Reach Maximum Drug Plasma Concentration After Multiple Doses (tmax,md) of Vericiguat on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Half-life Associated With the Terminal Slope (t1/2) of Vericiguat in Plasma on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Mean Residence Time (MRT) of Vericiguat in Plasma on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Percentage of Peak Trough Fluctuation (%PTF) on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Accumulation Ratio Calculated From Cmax After Multiple Dosing and Cmax After Single Dosing (RA,Cmax) on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Accumulation Ratio4 (RA4) on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Accumulation Ratio Calculated From AUCtau After Multiple Dosing and AUCtau After Single Dosing (RA,AUC) on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Amount of Drug Excreted via Urine (AE,ur[t1t2]) of Vericiguat on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Renal Clearance (CLR) of Vericiguat on Day 7Timeframe: 0-24 h (OD) and 0-12 h (BID) on Day 7
- Ratio of Maximum Drug Concentration to Concentration at 168 Hours After Multiple Doses (Cmax,md/C168) for Once Daily Vericiguat Treatment on Day 7Timeframe: 0-24 h on Day 7
- Ratio of Maximum Drug Concentration to Concentration at 156 Hours After Multiple Doses (Cmax,md/C156) for Twice Daily Vericiguat Treatment on Day 7Timeframe: 0-12 h on Day 7
Additional Information
Not Available
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