Clinical trial NCT00565565: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Heart Failure
Keywords: Biventriular chronic heart failure, Pulmonary hypertension
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2007-11-30
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Change in pulmonary capillary wedge pressure
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Change in mean pulmonary artery pressure
timeFrame: Pre-dose and up to 6 hr post-dose
measure: AUC
timeFrame: Pre-dose and up to 72 hr post-dose
measure: AUC/D
timeFrame: Pre-dose and up to 72 hr post-dose
measure: Cmax
timeFrame: Pre-dose and up to 72 hr post-dose
measure: Cmax/D
timeFrame: Pre-dose and up to 72 hr post-dose
measure: Number of participants with adverse events
timeFrame: Approximately 2 weeks
Secondary outcomes:
measure: Mean right atrial pressure
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Systolic pulmonary artery pressure
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Diastolic pulmonary artery pressure
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Heart rate
timeFrame: At pre-study visit, pre-dose and up to 24 hr post-dose
measure: Cardiac output
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Pulmonary vascular resistance
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Pulmonary vascular resistance index
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Systemic vascular resistance
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Systemic vascular resistance index
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Cardiac index
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Mean arterial pressure
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Systemic blood pressure
timeFrame: At pre-study visit, pre-dose and up to 24 hr post-dose
measure: Diastolic blood pressure
timeFrame: At pre-study visit, pre-dose and up to 24 hr post-dose
measure: Dyspnea Score
timeFrame: Pre-dose and up to 48 hr post-dose
measure: AUC(0-6)
timeFrame: Pre-dose and up to 6 hr post-dose
measure: AUCnorm
timeFrame: Pre-dose and up to 72 hr post-dose
measure: AUC(0-tn)
timeFrame: Pre-dose and up to 72 hr post-dose
measure: AUC(0-tn)norm
timeFrame: Pre-dose and up to 72 hr post-dose
measure: Cmax,norm
timeFrame: Pre-dose and up to 72 hr post-dose
measure: tmax
timeFrame: Pre-dose and up to 72 hr post-dose
measure: t½
timeFrame: Pre-dose and up to 72 hr post-dose
measure: Mean residence time
timeFrame: Pre-dose and up to 72 hr post-dose
measure: Total body clearance of drug from plasma calculated after oral administration (apparent oral clearance)
timeFrame: Pre-dose and up to 72 hr post-dose
measure: Apparent volume of distribution associated with the terminal phase (after oral administration)
timeFrame: Pre-dose and up to 72 hr post-dose
measure: Amount of drug excreted via urine
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Percent amount of drug excreted via urine
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Renal clearance of drug
timeFrame: Pre-dose and up to 6 hr post-dose
measure: Renin activity
timeFrame: Pre-dose and up to 24 hr post-dose
measure: Change from baseline of noradrenaline after drug administration
timeFrame: Pre-dose and up to 24 hr post-dose
measure: N-terminal pro-atrial natriuretic peptide
timeFrame: Pre-dose and up to 24 hr post-dose
measure: NT-pro B-type natriuretic peptide
timeFrame: Pre-dose and up to 24 hr post-dose
measure: Big endothelin-1
timeFrame: Pre-dose and up to 24 hr post-dose
measure: Cystatin C
timeFrame: Pre-dose and up to 24 hr post-dose
measure: Change from baseline of osteopontin after drug administration
timeFrame: Pre-dose and up to 24 hr post-dose
measure: Cyclic guanosine mono-phosphate
timeFrame: Pre-dose and up to 24 hr post-dose
Other outcomes:
Locations:
city: Bad Nauheim
country: Germany
state: Hessen
city: Gießen
country: Germany
state: Hessen
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
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.