Single Dose Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) Associated Pulmonary Hypertension.

Proof of Concept Study to Investigate Safety, Tolerability, Pharmacokinetics and the Impact on Pulmonary and Systemic Hemodynamics, Gas Exchange and Lung Function Parameters of a Single-dose of BAY63-2521 IR-tablet in Patients With COPD Associated Pulmonary Hypertension in an Non-randomized, Non-blinded Design

This study is to demonstrate the safety, tolerability, pharmakokinetic and pharmacodynamic effect of a single oral dose of BAY63-2521 in patients with pulmonary hypertension due to chronic obstructive pulmonary disease (COPD).

In addition to the pharmacodynamic and pharmacokinetic variables, the following laboratory variables were assessed:

• Hematology: Leucocytes, erythrocytes, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelets, white blood cell (WBC), partial thromboplastin time (PTT), prothrombin time (Quick), international normalized ratio (INR) (prothrombin time expressed in relation to normal value) ;
• Clinical chemistry: aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), gamma glutamyl transpeptidase (GGT), creatine phosphokinase (CK), lipase, cholinesterase (CHE), glucose, creatinine, urea, uric acid, bilirubin, total protein, serum albumin, sodium, potassium, calcium, chloride.

And due to the small number of subjects analyzed at several local labs, no summary statistics were provided.

Inclusion Criteria:

• Patients with pulmonary hypertension due to COPD, undergoing routine invasive measurement of hemodynamic parameters.
• Catheters for measurement of hemodynamic parameters (PAP [pulmonary artery pressure], PCWP [pulmonary capillary wedge pressure], CO [cardiac output], SBP [systolic blood pressure]) must be in place independent of the trial.

Exclusion Criteria:

• Acute exacerbation of COPD,
• Pre-existing lung disease other than COPD,
• Acute or severe chronic left heart failure,
• Severe coronary artery disease,
• Uncontrolled arterial hypertension;
• Severe left ventricular hypertrophy,
• Congenital or acquired valvular or myocardial disease,
• Systolic blood pressure < 100 mmHg,
• Heart rate < 55 bpm or >105 bpm,
• PaO2 (arterial partial oxygen pressure)/FiO2 (fraction of inspired oxygen) < 50 mmHg,
• PaCO2 (arterial partial pressure of carbon dioxide) > 55 mmHg,
• Severe hepatic insufficiency,
• Severe renal insufficiency.