check_circleStudy Completed

Clinical pharmacology

Bayer Identifier:

15357

ClinicalTrials.gov Identifier:

Not Available

EudraCT Number:

2012-000953-30

EU CT Number:

Not Available
Multiple Dose escalation Phase I study of BAY1021189

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.

Key Participants Requirements

Sex

Male

Age

18 - 45 Years
  • - 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

  • - 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
May 2012 - December 2013
Phase
Phase 1
Could I Receive a placebo
Yes
Products
Verquvo (Vericiguat, BAY1021189)
Accepts Healthy Volunteer
Yes

Where to participate

StatusInstitutionLocation
Completed
Wuppertal, 42113, Germany

Primary Outcome

  • Area Under the Plasma Concentration Versus Time Curve From Zero to Last Data Point (AUC[0tlast]) of Vericiguat on Day 1
    date_rangeTime Frame:
    0-24 h (OD) and 0-12 h (BID) on Day 1
  • Maximum Drug Plasma Concentration (Cmax) of Vericiguat on Day 1
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 Placebo
    date_rangeTime Frame:
    Baseline up to follow-up visit (10 days after last dose)
  • Change From Baseline in Heart Rate Over 1 Minute at Days 1 and 7
    date_rangeTime Frame:
    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 Output
    date_rangeTime Frame:
    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 Index
    date_rangeTime Frame:
    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 Rate
    date_rangeTime Frame:
    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 Volume
    date_rangeTime Frame:
    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 Resistance
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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)
    date_rangeTime Frame:
    Baseline up to follow-up visit (10 days after last dose)
  • Number of Subjects With Abnormal Clinical Laboratory Findings
    date_rangeTime Frame:
    Baseline up to follow-up visit (10 days after last dose)
  • Number of Subjects With Clinically Relevant Findings in Electrocardiogram (ECG) Parameters
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    0-24 h (OD) and 0-12 h (BID) on Day 1
  • Time to Reach Maximum Drug Plasma Concentration (tmax) of Vericiguat on Day 1
    date_rangeTime Frame:
    0-24 h (OD) and 0-12 h (BID) on Day 1
  • Mean Residence Time (MRT) of Vericiguat in Plasma on Day 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    0-48 h
  • Renal Clearance (CLR) of Vericiguat on Day 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    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 1
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    0-24 h (OD) and 0-12 h (BID) on Day 7
  • Mean Residence Time (MRT) of Vericiguat in Plasma on Day 7
    date_rangeTime Frame:
    0-24 h (OD) and 0-12 h (BID) on Day 7
  • Percentage of Peak Trough Fluctuation (%PTF) on Day 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    0-24 h (OD) and 0-12 h (BID) on Day 7
  • Accumulation Ratio4 (RA4) on Day 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    0-24 h (OD) and 0-12 h (BID) on Day 7
  • Renal Clearance (CLR) of Vericiguat on Day 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    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 7
    date_rangeTime Frame:
    0-12 h on Day 7

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