Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

Single Dose Escalation Study in Patients With Chronic Heart Failure

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00565565
First received: October 31, 2007
Last updated: August 9, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Heart Failure
Drug: BAY60-4552
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Change in pulmonary capillary wedge pressure [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Change in mean pulmonary artery pressure [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • AUC [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    Area under the plasma concentration vs time curve from zero to infinity after single dose

  • AUC/D [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    AUC divided by dose (mg)

  • Cmax [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    Maximum drug concentration in plasma after single dose administration

  • Cmax/D [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    Cmax divided by dose (mg)

  • Number of participants with adverse events [ Time Frame: Approximately 2 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Mean right atrial pressure [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Systolic pulmonary artery pressure [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Diastolic pulmonary artery pressure [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Heart rate [ Time Frame: At pre-study visit, pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: Yes ]
  • Cardiac output [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Pulmonary vascular resistance [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Pulmonary vascular resistance index [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Systemic vascular resistance [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Systemic vascular resistance index [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Cardiac index [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Mean arterial pressure [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Systemic blood pressure [ Time Frame: At pre-study visit, pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: Yes ]
  • Diastolic blood pressure [ Time Frame: At pre-study visit, pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: Yes ]
  • Dyspnea Score [ Time Frame: Pre-dose and up to 48 hr post-dose ] [ Designated as safety issue: No ]
    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) [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
    AUC from time 0 to 6 h after study drug intake

  • AUCnorm [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    AUC divided by dose (mg) per kg body weight

  • AUC(0-tn) [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    AUC from time 0 to the last data point

  • AUC(0-tn)norm [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    AUC(0-tn) divided by dose (mg) per kg body weight

  • Cmax,norm [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    Cmax divided by dose (mg) per kg body weight

  • tmax [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    Time to reach maximum drug concentration in plasma after single dose

  • t½ [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
    Half-life associated with the terminal slope

  • Mean residence time [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Apparent volume of distribution associated with the terminal phase (after oral administration) [ Time Frame: Pre-dose and up to 72 hr post-dose ] [ Designated as safety issue: No ]
  • Amount of drug excreted via urine [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Percent amount of drug excreted via urine [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Renal clearance of drug [ Time Frame: Pre-dose and up to 6 hr post-dose ] [ Designated as safety issue: No ]
  • Renin activity [ Time Frame: Pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: No ]
  • Change from baseline of noradrenaline after drug administration [ Time Frame: Pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: No ]
  • N-terminal pro-atrial natriuretic peptide [ Time Frame: Pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: No ]
  • NT-pro B-type natriuretic peptide [ Time Frame: Pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: No ]
  • Big endothelin-1 [ Time Frame: Pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: No ]
  • Cystatin C [ Time Frame: Pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: No ]
  • Change from baseline of osteopontin after drug administration [ Time Frame: Pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: No ]
  • Cyclic guanosine mono-phosphate [ Time Frame: Pre-dose and up to 24 hr post-dose ] [ Designated as safety issue: No ]

Enrollment: 55
Study Start Date: October 2007
Study Completion Date: April 2009
Primary Completion Date: December 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565565

Locations
Germany
Bad Nauheim, Hessen, Germany, 61231
Gießen, Hessen, Germany, 35392
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
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.

Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00565565     History of Changes
Other Study ID Numbers: 12356  2007-003216-54 
Study First Received: October 31, 2007
Last Updated: August 9, 2016
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
Biventriular chronic heart failure, Pulmonary hypertension

Additional relevant MeSH terms:
Heart Failure
Hypertension, Pulmonary
Heart Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 27, 2016