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Single Dose Escalation Study in Patients With Chronic Heart Failure

Primary Purpose

Heart Failure

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
BAY60-4552
Sponsored by
Bayer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure focused on measuring Biventriular chronic heart failure, Pulmonary hypertension

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients with chronic heart failure, undergoing routine invasive measurement of hemodynamic parameters

Exclusion Criteria:

  • Acute heart failure or acute decompensated heart failure, need for acute cardiologic intervention or surgery, severe renal or hepatic insufficiency, severe valvular disease

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

BAY60-4552, 1 mg

BAY60-4552, 2.5 mg

BAY60-4552, 5 mg

BAY60-4552, 7.5 mg

BAY60-4552, 10 mg

Arm Description

Subjects were planned to receive 1 mg of BAY60-4552 as solution

Subjects were planned to receive 2.5 mg of BAY60-4552 as tablet

Subjects were planned to receive 5.0 mg of BAY60-4552 as tablet

Subjects were planned to receive 7.5 mg of BAY60-4552 as tablet

Subjects were planned to receive 10 mg of BAY60-4552 as tablet

Outcomes

Primary Outcome Measures

Change in pulmonary capillary wedge pressure
Change in mean pulmonary artery pressure
AUC
Area under the plasma concentration vs time curve from zero to infinity after single dose
AUC/D
AUC divided by dose (mg)
Cmax
Maximum drug concentration in plasma after single dose administration
Cmax/D
Cmax divided by dose (mg)
Number of participants with adverse events

Secondary Outcome Measures

Mean right atrial pressure
Systolic pulmonary artery pressure
Diastolic pulmonary artery pressure
Heart rate
Cardiac output
Pulmonary vascular resistance
Pulmonary vascular resistance index
Systemic vascular resistance
Systemic vascular resistance index
Cardiac index
Mean arterial pressure
Systemic blood pressure
Diastolic blood pressure
Dyspnea Score
Subject is asked unpersuasively about his/her well-being in comparison to the baseline condition, measured on a 7-point Likert scale.
AUC(0-6)
AUC from time 0 to 6 h after study drug intake
AUCnorm
AUC divided by dose (mg) per kg body weight
AUC(0-tn)
AUC from time 0 to the last data point
AUC(0-tn)norm
AUC(0-tn) divided by dose (mg) per kg body weight
Cmax,norm
Cmax divided by dose (mg) per kg body weight
tmax
Time to reach maximum drug concentration in plasma after single dose
t½
Half-life associated with the terminal slope
Mean residence time
Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance)
Apparent volume of distribution associated with the terminal phase (after oral administration)
Amount of drug excreted via urine
Percent amount of drug excreted via urine
Renal clearance of drug
Renin activity
Change from baseline of noradrenaline after drug administration
N-terminal pro-atrial natriuretic peptide
NT-pro B-type natriuretic peptide
Big endothelin-1
Cystatin C
Change from baseline of osteopontin after drug administration
Cyclic guanosine mono-phosphate

Full Information

First Posted
October 31, 2007
Last Updated
August 9, 2016
Sponsor
Bayer
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1. Study Identification

Unique Protocol Identification Number
NCT00565565
Brief Title
Single Dose Escalation Study in Patients With Chronic Heart Failure
Official Title
Proof of Concept Study to Investigate Safety, Tolerability, Pharmacokinetics and the Impact on Pulmonary and Systemic Hemodynamics of a Single Oral Dose of BAY60-4552 in Patients With Biventricular Chronic Heart Failure and Pulmonary Hypertension in a Non-randomized, Non-blinded, Dose Escalation Design.
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
April 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is to demonstrate the safety and tolerability of a single oral dose of BAY60-4552 in a single dose escalation design. Furthermore, this study examines the changes in hemodynamics after application of the test substance.42 hospitalized stable patients with chronic heart failure will be included. Several measurements will be performed to test how good the drug works and wether there are any unwanted reactions to the drug (e.g. blood tests, ECG, heart rate, blood pressure, adverse events). After a observation period the patient will be discharged from the hospital.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure
Keywords
Biventriular chronic heart failure, Pulmonary hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
55 (Actual)

8. Arms, Groups, and Interventions

Arm Title
BAY60-4552, 1 mg
Arm Type
Experimental
Arm Description
Subjects were planned to receive 1 mg of BAY60-4552 as solution
Arm Title
BAY60-4552, 2.5 mg
Arm Type
Experimental
Arm Description
Subjects were planned to receive 2.5 mg of BAY60-4552 as tablet
Arm Title
BAY60-4552, 5 mg
Arm Type
Experimental
Arm Description
Subjects were planned to receive 5.0 mg of BAY60-4552 as tablet
Arm Title
BAY60-4552, 7.5 mg
Arm Type
Experimental
Arm Description
Subjects were planned to receive 7.5 mg of BAY60-4552 as tablet
Arm Title
BAY60-4552, 10 mg
Arm Type
Experimental
Arm Description
Subjects were planned to receive 10 mg of BAY60-4552 as tablet
Intervention Type
Drug
Intervention Name(s)
BAY60-4552
Intervention Description
Single dose escalation planned at dose of 1 mg, 2.5 mg, 5 mg, 7.5 mg, and 10 mg
Primary Outcome Measure Information:
Title
Change in pulmonary capillary wedge pressure
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Change in mean pulmonary artery pressure
Time Frame
Pre-dose and up to 6 hr post-dose
Title
AUC
Description
Area under the plasma concentration vs time curve from zero to infinity after single dose
Time Frame
Pre-dose and up to 72 hr post-dose
Title
AUC/D
Description
AUC divided by dose (mg)
Time Frame
Pre-dose and up to 72 hr post-dose
Title
Cmax
Description
Maximum drug concentration in plasma after single dose administration
Time Frame
Pre-dose and up to 72 hr post-dose
Title
Cmax/D
Description
Cmax divided by dose (mg)
Time Frame
Pre-dose and up to 72 hr post-dose
Title
Number of participants with adverse events
Time Frame
Approximately 2 weeks
Secondary Outcome Measure Information:
Title
Mean right atrial pressure
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Systolic pulmonary artery pressure
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Diastolic pulmonary artery pressure
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Heart rate
Time Frame
At pre-study visit, pre-dose and up to 24 hr post-dose
Title
Cardiac output
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Pulmonary vascular resistance
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Pulmonary vascular resistance index
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Systemic vascular resistance
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Systemic vascular resistance index
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Cardiac index
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Mean arterial pressure
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Systemic blood pressure
Time Frame
At pre-study visit, pre-dose and up to 24 hr post-dose
Title
Diastolic blood pressure
Time Frame
At pre-study visit, pre-dose and up to 24 hr post-dose
Title
Dyspnea Score
Description
Subject is asked unpersuasively about his/her well-being in comparison to the baseline condition, measured on a 7-point Likert scale.
Time Frame
Pre-dose and up to 48 hr post-dose
Title
AUC(0-6)
Description
AUC from time 0 to 6 h after study drug intake
Time Frame
Pre-dose and up to 6 hr post-dose
Title
AUCnorm
Description
AUC divided by dose (mg) per kg body weight
Time Frame
Pre-dose and up to 72 hr post-dose
Title
AUC(0-tn)
Description
AUC from time 0 to the last data point
Time Frame
Pre-dose and up to 72 hr post-dose
Title
AUC(0-tn)norm
Description
AUC(0-tn) divided by dose (mg) per kg body weight
Time Frame
Pre-dose and up to 72 hr post-dose
Title
Cmax,norm
Description
Cmax divided by dose (mg) per kg body weight
Time Frame
Pre-dose and up to 72 hr post-dose
Title
tmax
Description
Time to reach maximum drug concentration in plasma after single dose
Time Frame
Pre-dose and up to 72 hr post-dose
Title
t½
Description
Half-life associated with the terminal slope
Time Frame
Pre-dose and up to 72 hr post-dose
Title
Mean residence time
Time Frame
Pre-dose and up to 72 hr post-dose
Title
Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance)
Time Frame
Pre-dose and up to 72 hr post-dose
Title
Apparent volume of distribution associated with the terminal phase (after oral administration)
Time Frame
Pre-dose and up to 72 hr post-dose
Title
Amount of drug excreted via urine
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Percent amount of drug excreted via urine
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Renal clearance of drug
Time Frame
Pre-dose and up to 6 hr post-dose
Title
Renin activity
Time Frame
Pre-dose and up to 24 hr post-dose
Title
Change from baseline of noradrenaline after drug administration
Time Frame
Pre-dose and up to 24 hr post-dose
Title
N-terminal pro-atrial natriuretic peptide
Time Frame
Pre-dose and up to 24 hr post-dose
Title
NT-pro B-type natriuretic peptide
Time Frame
Pre-dose and up to 24 hr post-dose
Title
Big endothelin-1
Time Frame
Pre-dose and up to 24 hr post-dose
Title
Cystatin C
Time Frame
Pre-dose and up to 24 hr post-dose
Title
Change from baseline of osteopontin after drug administration
Time Frame
Pre-dose and up to 24 hr post-dose
Title
Cyclic guanosine mono-phosphate
Time Frame
Pre-dose and up to 24 hr post-dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients with chronic heart failure, undergoing routine invasive measurement of hemodynamic parameters Exclusion Criteria: Acute heart failure or acute decompensated heart failure, need for acute cardiologic intervention or surgery, severe renal or hepatic insufficiency, severe valvular disease
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Bad Nauheim
State/Province
Hessen
ZIP/Postal Code
61231
Country
Germany
City
Gießen
State/Province
Hessen
ZIP/Postal Code
35392
Country
Germany

12. IPD Sharing Statement

Citations:
Citation
Acute hemodynamic response to single oral doses of BAY 60-4552, a soluble guanylate cyclase stimulator, in patients with biventricular heart failure. V Mitrovic, B Swidnicki, A Ghofrani, W Mück, N Kirschbaum, J Mittendorf, J-P Stasch, G Wensing, R Frey, S Lentini. BMC Pharmacology 2009; 9(Suppl 1): P51.
Results Reference
result
Links:
URL
http://www.clinicaltrialsregister.eu/
Description
Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

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Single Dose Escalation Study in Patients With Chronic Heart Failure

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