Clinical trial NCT00640315: Single Dose Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) Associated Pulmonary Hypertension.
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hypertension, Pulmonary
Pulmonary Disease, Chronic Obstructive
Keywords: Chronic obstructive pulmonary disease
COPD
Pulmonary hypertension
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2008-03-21
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR)
timeFrame: From baseline up to 4 hours after administration
measure: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
measure: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose (AUC/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
measure: Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity Divided by Dose Per kg Body Weight (AUCnorm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
measure: Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
measure: Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
measure: Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
Secondary outcomes:
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI)
timeFrame: From baseline up to 4 hours after administration
measure: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index
timeFrame: From baseline up to 4 hours after administration
measure: Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2)
timeFrame: Baseline and 2 hours post dose
measure: Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2)
timeFrame: Baseline and 2 hours post dose
measure: Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2)
timeFrame: Baseline and 2 hours post dose
measure: Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2)
timeFrame: Baseline and 2 hours post dose
measure: Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 75% of Expiratory Vital Capacity (MEF75)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 50% of Expiratory Vital Capacity (MEF50)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 25% of Expiratory Vital Capacity (MEF25)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity at the Time When the DLCO is Measured (Alveolar Volume, VA)
timeFrame: Baseline and 2 hours post dose
measure: Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity
timeFrame: Baseline and 2 hours post dose
measure: Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Ventilation (V)
timeFrame: Baseline and 1 hour post dose
measure: Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Perfusion (Q)
timeFrame: Baseline and 1 hour post dose
measure: Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Dead Space Ventilation
timeFrame: Baseline and 1 hour post dose
measure: Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Low V/Q Perfusion
timeFrame: Baseline and 1 hour post dose
measure: Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Normal V/Q Perfusion
timeFrame: Baseline and 1 hour post dose
measure: Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hours Post Dose of Ventilation-perfusion Distribution Presented as Standard Deviation (SD) of Perfusion
timeFrame: Baseline and 1 hour post dose
measure: Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Ventilation-perfusion Distribution Presented as Standard Deviation (SD) of Ventilation
timeFrame: Baseline and 1 hour post dose
measure: Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Intrapulmonary Shunt Flow
timeFrame: Baseline and 1 hour post dose
measure: Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
measure: Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
measure: Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
measure: Area Under the Plasma Concentration Verse Time Curve From Zero to the Last Data Point (AUC0-tn) of Riociguat and Metabolite M1 After Single Dose of Riociguat
timeFrame: Study day 1: 0, 0.5, 1, 1.5, 2, 3, 4, 8, 12, 24, 36 hours post-dose; Study day 3: 0, 2, 6, 12, 24 hours post-dose
Other outcomes:
measure: Mean PR Duration (PRmean) - Change From Baseline to Day 3
timeFrame: Baseline and day 3
measure: Mean QRS Duration (QRSmean) - Change From Baseline to Day 3
timeFrame: Baseline and day 3
measure: Mean QT Duration (QTmean) - Change From Baseline to Day 3
timeFrame: Baseline and day 3
measure: Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Day 3
timeFrame: Baseline and day 3
measure: Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Day 3
timeFrame: Baseline and day 3
Locations:
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Löwenstein
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Bad Nauheim
country: Germany
state: Hessen
city: Gießen
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Dresden
country: Germany
state: Sachsen
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: H.-A. Ghofrani, G. Staehler, E. Gruenig, M. Halank, V. Mitrovic, S. Unger, W. Mueck, R. Frey, J. Behr. The Effect Of The Soluble Guanylate Cyclase Stimulator Riociguat On Hemodynamics In Patients With Pulmonary Hypertension Due To Chronic Obstructive Pulmonary Disease. D96 CLINICAL TRIALS AND OUTCOMES IN PULMONARY HYPERTENSION.