Single Dose Escalation Study in Patients With Chronic Heart Failure

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.

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure
• Intervention / Treatment: Drug: BAY60-4552

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Hessen
    • Bad Nauheim, Hessen, Germany, 61231
    • Gießen, Hessen, Germany, 35392

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BAY60-4552, 1 mg; Subjects were planned to receive 1 mg of BAY60-4552 as solution	Drug: BAY60-4552; Single dose escalation planned at dose of 1 mg, 2.5 mg, 5 mg, 7.5 mg, and 10 mg
Experimental: BAY60-4552, 2.5 mg; Subjects were planned to receive 2.5 mg of BAY60-4552 as tablet	Drug: BAY60-4552; Single dose escalation planned at dose of 1 mg, 2.5 mg, 5 mg, 7.5 mg, and 10 mg
Experimental: BAY60-4552, 5 mg; Subjects were planned to receive 5.0 mg of BAY60-4552 as tablet	Drug: BAY60-4552; Single dose escalation planned at dose of 1 mg, 2.5 mg, 5 mg, 7.5 mg, and 10 mg
Experimental: BAY60-4552, 7.5 mg; Subjects were planned to receive 7.5 mg of BAY60-4552 as tablet	Drug: BAY60-4552; Single dose escalation planned at dose of 1 mg, 2.5 mg, 5 mg, 7.5 mg, and 10 mg
Experimental: BAY60-4552, 10 mg; Subjects were planned to receive 10 mg of BAY60-4552 as tablet	Drug: BAY60-4552; Single dose escalation planned at dose of 1 mg, 2.5 mg, 5 mg, 7.5 mg, and 10 mg

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in pulmonary capillary wedge pressure		Pre-dose and up to 6 hr post-dose
Change in mean pulmonary artery pressure		Pre-dose and up to 6 hr post-dose
AUC	Area under the plasma concentration vs time curve from zero to infinity after single dose	Pre-dose and up to 72 hr post-dose
AUC/D	AUC divided by dose (mg)	Pre-dose and up to 72 hr post-dose
Cmax	Maximum drug concentration in plasma after single dose administration	Pre-dose and up to 72 hr post-dose
Cmax/D	Cmax divided by dose (mg)	Pre-dose and up to 72 hr post-dose
Number of participants with adverse events		Approximately 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean right atrial pressure		Pre-dose and up to 6 hr post-dose
Systolic pulmonary artery pressure		Pre-dose and up to 6 hr post-dose
Diastolic pulmonary artery pressure		Pre-dose and up to 6 hr post-dose
Heart rate		At pre-study visit, pre-dose and up to 24 hr post-dose
Cardiac output		Pre-dose and up to 6 hr post-dose
Pulmonary vascular resistance		Pre-dose and up to 6 hr post-dose
Pulmonary vascular resistance index		Pre-dose and up to 6 hr post-dose
Systemic vascular resistance		Pre-dose and up to 6 hr post-dose
Systemic vascular resistance index		Pre-dose and up to 6 hr post-dose
Cardiac index		Pre-dose and up to 6 hr post-dose
Mean arterial pressure		Pre-dose and up to 6 hr post-dose
Systemic blood pressure		At pre-study visit, pre-dose and up to 24 hr post-dose
Diastolic blood pressure		At pre-study visit, pre-dose and up to 24 hr post-dose
Dyspnea Score	Subject is asked unpersuasively about his/her well-being in comparison to the baseline condition, measured on a 7-point Likert scale.	Pre-dose and up to 48 hr post-dose
AUC(0-6)	AUC from time 0 to 6 h after study drug intake	Pre-dose and up to 6 hr post-dose
AUCnorm	AUC divided by dose (mg) per kg body weight	Pre-dose and up to 72 hr post-dose
AUC(0-tn)	AUC from time 0 to the last data point	Pre-dose and up to 72 hr post-dose
AUC(0-tn)norm	AUC(0-tn) divided by dose (mg) per kg body weight	Pre-dose and up to 72 hr post-dose
Cmax,norm	Cmax divided by dose (mg) per kg body weight	Pre-dose and up to 72 hr post-dose
tmax	Time to reach maximum drug concentration in plasma after single dose	Pre-dose and up to 72 hr post-dose
t½	Half-life associated with the terminal slope	Pre-dose and up to 72 hr post-dose
Mean residence time		Pre-dose and up to 72 hr post-dose
Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance)		Pre-dose and up to 72 hr post-dose
Apparent volume of distribution associated with the terminal phase (after oral administration)		Pre-dose and up to 72 hr post-dose
Amount of drug excreted via urine		Pre-dose and up to 6 hr post-dose
Percent amount of drug excreted via urine		Pre-dose and up to 6 hr post-dose
Renal clearance of drug		Pre-dose and up to 6 hr post-dose
Renin activity		Pre-dose and up to 24 hr post-dose
Change from baseline of noradrenaline after drug administration		Pre-dose and up to 24 hr post-dose
N-terminal pro-atrial natriuretic peptide		Pre-dose and up to 24 hr post-dose
NT-pro B-type natriuretic peptide		Pre-dose and up to 24 hr post-dose
Big endothelin-1		Pre-dose and up to 24 hr post-dose
Cystatin C		Pre-dose and up to 24 hr post-dose
Change from baseline of osteopontin after drug administration		Pre-dose and up to 24 hr post-dose
Cyclic guanosine mono-phosphate		Pre-dose and up to 24 hr post-dose

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

General Publications

• 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.

Helpful Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): April 1, 2009

Study Registration Dates

• First Submitted: October 31, 2007
• First Submitted That Met QC Criteria: November 29, 2007
• First Posted (Estimate): November 30, 2007

Study Record Updates

• Last Update Posted (Estimate): August 10, 2016
• Last Update Submitted That Met QC Criteria: August 9, 2016
• Last Verified: August 1, 2016

More Information

Terms related to this study

• Keywords: Biventriular chronic heart failure, Pulmonary hypertension
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 12356; 2007-003216-54 (EudraCT Number)