Hypertension, Pulmonary, Pulmonary Disease, Chronic Obstructive
Conditions
Keywords
Chronic obstructive pulmonary disease, COPD, Pulmonary hypertension
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.
Interventions
DRUGRiociguat (Adempas, BAY63-2521) 1.0 mg
1.0 mg BAY63-2521 will be given twice per subject, as single dose administration during the hemodynamic investigation (on study day 1) and during the lung function testing (on study day 3).
DRUGRiociguat (Adempas, BAY63-2521) 2.5 mg
2.5 mg BAY63-2521 will be given twice per subject, as single dose administration during the hemodynamic investigation (on study day 1) and during the lung function testing (on study day 3).
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | 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 | — |
| Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | 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 | — |
| Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | 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 | — |
| 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 | 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 | — |
| 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 | 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 | — |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean) | From baseline up to 4 hours after administration | PAPmean was reported during right heart catheterization |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR) | From baseline up to 4 hours after administration | PVR was calculated according to the formula PVR = 80\*(PAPmean - pulmonary capillary wedge pressure)/cardiac output |
| Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | 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
| Measure | Time frame | Description |
|---|---|---|
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP) | From baseline up to 4 hours after administration | MAP was acquired during right heart catheterization |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO) | From baseline up to 4 hours after administration | CO was measured in triplicate by the thermodilution technique |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI) | From baseline up to 4 hours after administration | PVRI was calculated as PVRI = (80\*(PAPmean - PCWP)/CO)\*body surface area |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR) | From baseline up to 4 hours after administration | SVR was calculated as SVR = 80\*(MAP-RAPmean)/CO |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI) | From baseline up to 4 hours after administration | SVRI was calculated as SVRI = (80\*(MAP - RAPmean)/CO)\*body surface area |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index | From baseline up to 4 hours after administration | Cardiac index was calculated as cardiac index = CO / body surface area. |
| Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2) | Baseline and 2 hours post dose | Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline. |
| Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | Baseline and 2 hours post dose | Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline. |
| Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2) | Baseline and 2 hours post dose | Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline. |
| Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2) | Baseline and 2 hours post dose | Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline. |
| Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2) | Baseline and 2 hours post dose | Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline. |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1 | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC | Baseline and 2 hours post dose | The percent of predicted TLC was provided by investigator at site. |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 75% of Expiratory Vital Capacity (MEF75) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 50% of Expiratory Vital Capacity (MEF50) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 25% of Expiratory Vital Capacity (MEF25) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | Baseline and 2 hours post dose | — |
| 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) | Baseline and 2 hours post dose | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity | Baseline and 2 hours post dose | — |
| Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Ventilation (V) | Baseline and 1 hour post dose | — |
| Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Perfusion (Q) | Baseline and 1 hour post dose | — |
| Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Dead Space Ventilation | Baseline and 1 hour post dose | — |
| Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Low V/Q Perfusion | Baseline and 1 hour post dose | — |
| Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Normal V/Q Perfusion | Baseline and 1 hour post dose | — |
| 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 | Baseline and 1 hour post dose | — |
| 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 | Baseline and 1 hour post dose | — |
| Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Intrapulmonary Shunt Flow | Baseline and 1 hour post dose | — |
| Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | 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 | — |
| Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | 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 | — |
| Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | 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 | — |
| 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 | 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 | — |
| Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC | Baseline and 2 hours post dose | — |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean) | From baseline up to 4 hours after administration | RAPmean was reported during right heart catheterization |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst) | From baseline up to 4 hours after administration | PAPsyst was acquired during right heart catheterization |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast) | From baseline up to 4 hours after administration | PAPdiast was acquired during right heart catheterization |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP) | From baseline up to 4 hours after administration | PCWP was acquired during right heart catheterization |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR) | From baseline up to 4 hours after administration | HR was acquired during right heart catheterization |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP) | From baseline up to 4 hours after administration | Systolic arterial blood pressure was acquired during right heart catheterization. |
| Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP) | From baseline up to 4 hours after administration | Diastolic arterial blood pressure was acquired during right heart catheterization. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mean PR Duration (PRmean) - Change From Baseline to Day 3 | Baseline and day 3 | PR duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. |
| Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Day 3 | Baseline and day 3 | Fridericia-corrected QTcF duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. |
| Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Day 3 | Baseline and day 3 | Bazett-corrected QTcB duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. |
| Mean QT Duration (QTmean) - Change From Baseline to Day 3 | Baseline and day 3 | QT duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. |
| Mean QRS Duration (QRSmean) - Change From Baseline to Day 3 | Baseline and day 3 | QRS duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position. |
Countries
Germany
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg Participants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3. | 10 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg Participants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3. | 13 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Riociguat (Adempas, BAY63-2521) 1.0 mg | Riociguat (Adempas, BAY63-2521) 2.5 mg | Total |
|---|---|---|---|
| Age, Continuous | 67.5 Years STANDARD_DEVIATION 8.9 | 69.2 Years STANDARD_DEVIATION 5.7 | 68.4 Years STANDARD_DEVIATION 7.1 |
| Gender Female | 5 Participants | 6 Participants | 11 Participants |
| Gender Male | 5 Participants | 7 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 10 | 6 / 13 |
| serious Total, serious adverse events | 0 / 10 | 2 / 13 |
Outcome results
Primary
Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 481.9 µg*h/L | Geometric Coefficient of Variation 65.3 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 605.5 µg*h/L | Geometric Coefficient of Variation 79.1 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | NA µg*h/L | — |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | NA µg*h/L | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | NA µg*h/L | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 1319 µg*h/L | Geometric Coefficient of Variation 56.8 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 1019 µg*h/L | Geometric Coefficient of Variation 26 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 999.5 µg*h/L | Geometric Coefficient of Variation 61.6 |
Primary
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
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Riociguat - Study day 1 (00d01h) | 481.9 10^3*h/L | Geometric Coefficient of Variation 65.3 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Riociguat - Study day 3 (02d01h) | 605.5 10^3*h/L | Geometric Coefficient of Variation 79.1 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Metabolite M1 - Study day 1 (00d01h) | NA 10^3*h/L | — |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Metabolite M1 - Study day 3 (02d01h) | NA 10^3*h/L | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Metabolite M1 - Study day 3 (02d01h) | NA 10^3*h/L | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Riociguat - Study day 1 (00d01h) | 527.4 10^3*h/L | Geometric Coefficient of Variation 56.8 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Metabolite M1 - Study day 1 (00d01h) | 421.6 10^3*h/L | Geometric Coefficient of Variation 26 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Riociguat - Study day 3 (02d01h) | 399.8 10^3*h/L | Geometric Coefficient of Variation 61.6 |
Primary
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
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Riociguat - Study day 1 (00d01h) | 35.53 kg*h/L | Geometric Coefficient of Variation 62.6 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Riociguat - Study day 3 (02d01h) | 44.86 kg*h/L | Geometric Coefficient of Variation 68 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Metabolite M1 - Study day 1 (00d01h) | NA kg*h/L | — |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Metabolite M1 - Study day 3 (02d01h) | NA kg*h/L | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Metabolite M1 - Study day 3 (02d01h) | NA kg*h/L | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Riociguat - Study day 1 (00d01h) | 38.85 kg*h/L | Geometric Coefficient of Variation 56.7 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Metabolite M1 - Study day 1 (00d01h) | 31.03 kg*h/L | Geometric Coefficient of Variation 27.1 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Riociguat - Study day 3 (02d01h) | 29.93 kg*h/L | Geometric Coefficient of Variation 65.7 |
Primary
Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 42.96 µg/L | Geometric Coefficient of Variation 32.3 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 35.30 µg/L | Geometric Coefficient of Variation 46 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 10.44 µg/L | Geometric Coefficient of Variation 56.5 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | 9.869 µg/L | Geometric Coefficient of Variation 37.2 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | 26.49 µg/L | Geometric Coefficient of Variation 26.5 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 116.0 µg/L | Geometric Coefficient of Variation 36 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 27.27 µg/L | Geometric Coefficient of Variation 34.9 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 80.44 µg/L | Geometric Coefficient of Variation 27.3 |
Primary
Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 42.96 10^3/L | Geometric Coefficient of Variation 32.3 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 35.30 10^3/L | Geometric Coefficient of Variation 46 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 10.80 10^3/L | Geometric Coefficient of Variation 56.5 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | 10.21 10^3/L | Geometric Coefficient of Variation 37.2 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | 10.96 10^3/L | Geometric Coefficient of Variation 26.5 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 46.42 10^3/L | Geometric Coefficient of Variation 36 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 11.28 10^3/L | Geometric Coefficient of Variation 34.9 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 32.18 10^3/L | Geometric Coefficient of Variation 27.3 |
Primary
Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 3.185 kg/L | Geometric Coefficient of Variation 27 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 2.617 kg/L | Geometric Coefficient of Variation 39.1 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 0.800 kg/L | Geometric Coefficient of Variation 46.8 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | 0.757 kg/L | Geometric Coefficient of Variation 26.8 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | 0.807 kg/L | Geometric Coefficient of Variation 27.5 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 3.419 kg/L | Geometric Coefficient of Variation 30.9 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 0.831 kg/L | Geometric Coefficient of Variation 31.7 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Maximum Drug Concentration in Plasma Divided by Dose Per kg Body Weight (Cmax,Norm) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 2.370 kg/L | Geometric Coefficient of Variation 31.4 |
Primary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean)
PAPmean was reported during right heart catheterization
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean) | -3.60 mmHg | Standard Deviation 3.41 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean) | -4.83 mmHg | Standard Deviation 4.17 |
Primary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR)
PVR was calculated according to the formula PVR = 80\*(PAPmean - pulmonary capillary wedge pressure)/cardiac output
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR) | -58.32 (dyn*s*cm^-5) | Standard Deviation 50.46 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR) | -123.8 (dyn*s*cm^-5) | Standard Deviation 73.53 |
Secondary
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
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Riociguat - Study day 1 (00d01h) | 426.3 µg*h/L | Geometric Coefficient of Variation 66.1 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Riociguat - Study day 3 (02d01h) | 294.7 µg*h/L | Geometric Coefficient of Variation 81.6 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Metabolite M1 - Study day 1 (00d01h) | 200.1 µg*h/L | Geometric Coefficient of Variation 76.6 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | Metabolite M1 - Study day 3 (02d01h) | 139.4 µg*h/L | Geometric Coefficient of Variation 98.8 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Metabolite M1 - Study day 3 (02d01h) | 490.6 µg*h/L | Geometric Coefficient of Variation 29.1 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Riociguat - Study day 1 (00d01h) | 1196 µg*h/L | Geometric Coefficient of Variation 55.8 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Metabolite M1 - Study day 1 (00d01h) | 727.4 µg*h/L | Geometric Coefficient of Variation 20.1 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | Riociguat - Study day 3 (02d01h) | 750.3 µg*h/L | Geometric Coefficient of Variation 41.3 |
Secondary
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2)
Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline.
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2) | -2.23 Percentage | Standard Deviation 3.89 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2) | -2.89 Percentage | Standard Deviation 3.84 |
Secondary
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2)
Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline.
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2) | -12.64 Percentage | Standard Deviation 24.79 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2) | -12.99 Percentage | Standard Deviation 14 |
Secondary
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2)
Arterial blood gas analysis was performed by insertion of an indwelling arterial cannula. Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline.
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | 4.43 Percentage | Standard Deviation 20.93 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2) | 4.04 Percentage | Standard Deviation 13.27 |
Secondary
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2)
Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline.
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2) | 0.87 Percentage | Standard Deviation 8.57 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2) | 12.07 Percentage | Standard Deviation 10.53 |
Secondary
Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2)
Percent change was calculated as 100%\*(value post dose - value at baseline)/ value at baseline.
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2) | 0.27 Percentage | Standard Deviation 6.58 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2) | 6.76 Percentage | Standard Deviation 6.1 |
Secondary
Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 8.422 hour | Geometric Coefficient of Variation 58.6 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 12.18 hour | Geometric Coefficient of Variation 47.5 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | NA hour | — |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | NA hour | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | NA hour | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 9.541 hour | Geometric Coefficient of Variation 50.7 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 20.57 hour | Geometric Coefficient of Variation 46.4 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 8.835 hour | Geometric Coefficient of Variation 50.8 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Diffusing Capacity of the Lung for Carbon Monoxide (DLCO)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | 15.67 Percentage | Standard Deviation 26.65 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) | 18.66 Percentage | Standard Deviation 17.39 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC | -0.69 Percentage | Standard Deviation 11.26 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC | -1.29 Percentage | Standard Deviation 17.98 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1) | 2.90 Percentage | Standard Deviation 3.32 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1) | 3.81 Percentage | Standard Deviation 11.55 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC) | 5.16 Percentage | Standard Deviation 16.08 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC) | 8.62 Percentage | Standard Deviation 23.73 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 25% of Expiratory Vital Capacity (MEF25)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 25% of Expiratory Vital Capacity (MEF25) | 8.56 Percentage | Standard Deviation 29.57 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 25% of Expiratory Vital Capacity (MEF25) | -0.61 Percentage | Standard Deviation 40.44 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 50% of Expiratory Vital Capacity (MEF50)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 50% of Expiratory Vital Capacity (MEF50) | 0.17 Percentage | Standard Deviation 18.29 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 50% of Expiratory Vital Capacity (MEF50) | 5.59 Percentage | Standard Deviation 15.03 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 75% of Expiratory Vital Capacity (MEF75)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 75% of Expiratory Vital Capacity (MEF75) | -0.92 Percentage | Standard Deviation 22.28 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 75% of Expiratory Vital Capacity (MEF75) | -1.09 Percentage | Standard Deviation 17.38 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1 | 3.00 Percentage | Standard Deviation 3.38 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1 | 4.35 Percentage | Standard Deviation 11.88 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC | 0.41 Percentage | Standard Deviation 8.01 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC | 8.65 Percentage | Standard Deviation 23.77 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV | 0.83 Percentage | Standard Deviation 9.09 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV | 3.21 Percentage | Standard Deviation 22.46 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC
The percent of predicted TLC was provided by investigator at site.
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC | 1.91 Percentage | Standard Deviation 10.63 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC | 2.08 Percentage | Standard Deviation 10.92 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC | 7.60 Percentage | Standard Deviation 22.89 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC | 10.00 Percentage | Standard Deviation 20.45 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV) | 0.80 Percentage | Standard Deviation 9.15 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV) | 3.16 Percentage | Standard Deviation 22.39 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity | 20.77 Percentage | Standard Deviation 27.36 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity | 18.61 Percentage | Standard Deviation 16.49 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw) | -5.78 Percentage | Standard Deviation 24.03 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw) | -5.89 Percentage | Standard Deviation 34.27 |
Secondary
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)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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) | -2.35 Percentage | Standard Deviation 6.9 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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) | 1.72 Percentage | Standard Deviation 12.79 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC) | 1.86 Percentage | Standard Deviation 10.53 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC) | 2.14 Percentage | Standard Deviation 10.85 |
Secondary
Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC)
Time frame: Baseline and 2 hours post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC) | 7.55 Percentage | Standard Deviation 22.35 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC) | 10.09 Percentage | Standard Deviation 20.5 |
Secondary
Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 12.92 hour | Geometric Coefficient of Variation 50.2 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 18.88 hour | Geometric Coefficient of Variation 39.5 |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | NA hour | — |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | NA hour | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | NA hour | — |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 13.97 hour | Geometric Coefficient of Variation 46.5 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 34.77 hour | Geometric Coefficient of Variation 41.1 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 13.37 hour | Geometric Coefficient of Variation 46.5 |
Secondary
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Dead Space Ventilation
Time frame: Baseline and 1 hour post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Dead Space Ventilation | 3.20 Percentage of total ventilation | Standard Deviation 8.5 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Dead Space Ventilation | -42.50 Percentage of total ventilation | — |
Secondary
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Intrapulmonary Shunt Flow
Time frame: Baseline and 1 hour post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Intrapulmonary Shunt Flow | -1.10 Percentage of total perfusion | Standard Deviation 1.7 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Intrapulmonary Shunt Flow | -0.30 Percentage of total perfusion | — |
Secondary
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Low V/Q Perfusion
Time frame: Baseline and 1 hour post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Low V/Q Perfusion | 3.00 Percentage | Standard Deviation 13.4 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Low V/Q Perfusion | -0.30 Percentage | — |
Secondary
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Normal V/Q Perfusion
Time frame: Baseline and 1 hour post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Normal V/Q Perfusion | -9.80 Percentage | Standard Deviation 21 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Normal V/Q Perfusion | 4.10 Percentage | — |
Secondary
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Perfusion (Q)
Time frame: Baseline and 1 hour post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Perfusion (Q) | 0.30 L/min | Standard Deviation 0.5 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Perfusion (Q) | -0.40 L/min | Standard Deviation 0.5 |
Secondary
Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Ventilation (V)
Time frame: Baseline and 1 hour post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Ventilation (V) | -0.90 L/min | Standard Deviation 1 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Ventilation (V) | -0.10 L/min | Standard Deviation 0.2 |
Secondary
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
Time frame: Baseline and 1 hour post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | -0.10 L/MIN | Standard Deviation 0.4 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | -0.50 L/MIN | — |
Secondary
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
Time frame: Baseline and 1 hour post dose
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | 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 | 0.00 L/MIN | Standard Deviation 0.1 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | 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 | -0.10 L/MIN | — |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index
Cardiac index was calculated as cardiac index = CO / body surface area.
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index | 0.35 L/min/m^2 | Standard Deviation 0.26 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index | 0.89 L/min/m^2 | Standard Deviation 0.83 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO)
CO was measured in triplicate by the thermodilution technique
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO) | 0.66 L/min | Standard Deviation 0.48 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO) | 1.61 L/min | Standard Deviation 1.49 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP)
Diastolic arterial blood pressure was acquired during right heart catheterization.
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP) | -13.50 mmHg | Standard Deviation 6.84 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP) | -11.25 mmHg | Standard Deviation 9.5 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast)
PAPdiast was acquired during right heart catheterization
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast) | -3.80 mmHg | Standard Deviation 4.73 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast) | -3.25 mmHg | Standard Deviation 2.83 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR)
HR was acquired during right heart catheterization
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR) | 9.40 beats per minute | Standard Deviation 7.31 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR) | 13.92 beats per minute | Standard Deviation 8.68 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP)
MAP was acquired during right heart catheterization
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP) | -17.10 mmHg | Standard Deviation 7.71 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP) | -13.92 mmHg | Standard Deviation 8.03 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean)
RAPmean was reported during right heart catheterization
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean) | -2.00 mmHg | Standard Deviation 1.41 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean) | -0.64 mmHg | Standard Deviation 1.69 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP)
PCWP was acquired during right heart catheterization
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP) | -3.60 mmHg | Standard Deviation 3.57 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP) | -1.17 mmHg | Standard Deviation 3.38 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI)
PVRI was calculated as PVRI = (80\*(PAPmean - PCWP)/CO)\*body surface area
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI) | -108.6 dyn*s*cm^-5*m^2 | Standard Deviation 93.46 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI) | -222.1 dyn*s*cm^-5*m^2 | Standard Deviation 130.69 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI)
SVRI was calculated as SVRI = (80\*(MAP - RAPmean)/CO)\*body surface area
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI) | -836.4 dyn*s*cm^-5*m^2 | Standard Deviation 385.92 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI) | -837.9 dyn*s*cm^-5*m^2 | Standard Deviation 276.17 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR)
SVR was calculated as SVR = 80\*(MAP-RAPmean)/CO
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR) | -440.0 dyn*s*cm^-5 | Standard Deviation 205.78 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR) | -467.7 dyn*s*cm^-5 | Standard Deviation 154.94 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP)
Systolic arterial blood pressure was acquired during right heart catheterization.
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP) | -26.30 mmHg | Standard Deviation 16.63 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP) | -22.17 mmHg | Standard Deviation 15.24 |
Secondary
Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst)
PAPsyst was acquired during right heart catheterization
Time frame: From baseline up to 4 hours after administration
Population: per-protocol population (subjects with data available for this outcome measure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst) | -6.90 mmHg | Standard Deviation 4.86 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst) | -9.42 mmHg | Standard Deviation 6.73 |
Secondary
Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat
Time frame: 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
Population: per-protocol population
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 1.75 hour |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 2.033 hour |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 11.97 hour |
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | 9.017 hour |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 3 (02d01h) | 12.04 hour |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 1 (00d01h) | 1.742 hour |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Metabolite M1 - Study day 1 (00d01h) | 10.04 hour |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat | Riociguat - Study day 3 (02d01h) | 2.042 hour |
Other Pre-specified
Mean PR Duration (PRmean) - Change From Baseline to Day 3
PR duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time frame: Baseline and day 3
Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean PR Duration (PRmean) - Change From Baseline to Day 3 | 0.64 msec | Standard Deviation 21.6 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean PR Duration (PRmean) - Change From Baseline to Day 3 | 11.20 msec | Standard Deviation 27.57 |
Other Pre-specified
Mean QRS Duration (QRSmean) - Change From Baseline to Day 3
QRS duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time frame: Baseline and day 3
Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean QRS Duration (QRSmean) - Change From Baseline to Day 3 | -2.56 msec | Standard Deviation 5.79 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean QRS Duration (QRSmean) - Change From Baseline to Day 3 | 0.68 msec | Standard Deviation 12.99 |
Other Pre-specified
Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Day 3
Bazett-corrected QTcB duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time frame: Baseline and day 3
Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Day 3 | -1.45 msec | Standard Deviation 23.08 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Day 3 | 0.95 msec | Standard Deviation 13.49 |
Other Pre-specified
Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Day 3
Fridericia-corrected QTcF duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time frame: Baseline and day 3
Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Day 3 | -1.58 msec | Standard Deviation 20.15 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Day 3 | -12.73 msec | Standard Deviation 10.5 |
Other Pre-specified
Mean QT Duration (QTmean) - Change From Baseline to Day 3
QT duration was evaluated as part of the 12-lead electrocardiogram. ECGs were recorded after the participant had been at rest for 15 minutes in a supine position.
Time frame: Baseline and day 3
Population: All subjects who received at least one dose of the trial medication were included in the safety evaluation.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Riociguat (Adempas, BAY63-2521) 1.0 mg | Mean QT Duration (QTmean) - Change From Baseline to Day 3 | -2.00 msec | Standard Deviation 22.03 |
| Riociguat (Adempas, BAY63-2521) 2.5 mg | Mean QT Duration (QTmean) - Change From Baseline to Day 3 | -36.88 msec | Standard Deviation 15.48 |