Phase 1
N=23
Single Dose Study in Patients With Chronic Obstructive Pulmonary Disease (COPD) Associated Pulmonary Hypertension.
Hypertension, Pulmonary · Pulmonary Disease, Chronic Obstructive
Bottom Line
View on ClinicalTrials.gov: NCT00640315 ↗Enrolled (actual)
23
Serious AEs
8.7%
Results posted
Feb 2014
Primary outcome: Primary: Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean) — -3.60; -4.83 mmHg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Riociguat (Adempas, BAY63-2521) 1.0 mg (Drug); Riociguat (Adempas, BAY63-2521) 2.5 mg (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Bayer
- Primary completion
- Sep 2009
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean) |
-3.60; -4.83 | — |
| PRIMARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR) |
-58.32; -123.8 | — |
| PRIMARY Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat |
481.9; 1319; 605.5; 999.5; NA; 1019 | — |
| 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 |
481.9; 527.4; 605.5; 399.8; NA; 421.6 | — |
| 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 |
35.53; 38.85; 44.86; 29.93; NA; 31.03 | — |
| PRIMARY Maximum Drug Concentration in Plasma (Cmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat |
42.96; 116.0; 35.30; 80.44; 10.44; 27.27 | — |
| PRIMARY Maximum Drug Concentration in Plasma Divided by Dose (Cmax/D) of Riociguat and Metabolite M1 After Single Dose of Riociguat |
42.96; 46.42; 35.30; 32.18; 10.80; 11.28 | — |
| 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 |
3.185; 3.419; 2.617; 2.370; 0.800; 0.831 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean) |
-2.00; -0.64 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst) |
-6.90; -9.42 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast) |
-3.80; -3.25 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP) |
-3.60; -1.17 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR) |
9.40; 13.92 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP) |
-26.30; -22.17 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP) |
-13.50; -11.25 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP) |
-17.10; -13.92 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO) |
0.66; 1.61 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI) |
-108.6; -222.1 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR) |
-440.0; -467.7 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI) |
-836.4; -837.9 | — |
| SECONDARY Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index |
0.35; 0.89 | — |
| SECONDARY Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2) |
-12.64; -12.99 | — |
| SECONDARY Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2) |
4.43; 4.04 | — |
| SECONDARY Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2) |
0.87; 12.07 | — |
| SECONDARY Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2) |
-2.23; -2.89 | — |
| SECONDARY Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2) |
0.27; 6.76 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1) |
2.90; 3.81 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1 |
3.00; 4.35 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC) |
5.16; 8.62 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC |
0.41; 8.65 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC |
-0.69; -1.29 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC) |
1.86; 2.14 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC |
1.91; 2.08 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV) |
0.80; 3.16 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV |
0.83; 3.21 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 75% of Expiratory Vital Capacity (MEF75) |
-0.92; -1.09 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 50% of Expiratory Vital Capacity (MEF50) |
0.17; 5.59 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Maximal Expiratory Flow at 25% of Expiratory Vital Capacity (MEF25) |
8.56; -0.61 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw) |
-5.78; -5.89 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC) |
7.55; 10.09 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC |
7.60; 10.00 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Diffusing Capacity of the Lung for Carbon Monoxide (DLCO) |
15.67; 18.66 | — |
| 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) |
-2.35; 1.72 | — |
| SECONDARY Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity |
20.77; 18.61 | — |
| SECONDARY Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Ventilation (V) |
-0.90; -0.10 | — |
| SECONDARY Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Total Perfusion (Q) |
0.30; -0.40 | — |
| SECONDARY Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Dead Space Ventilation |
3.20; -42.50 | — |
| SECONDARY Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Low V/Q Perfusion |
3.00; -0.30 | — |
| SECONDARY Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Normal V/Q Perfusion |
-9.80; 4.10 | — |
| 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 |
0.00; -0.10 | — |
| 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 |
-0.10; -0.50 | — |
| SECONDARY Multiple Inert Gas Elimination Technique (MIGET) Analysis - Change From Baseline at 1 Hour Post Dose of Intrapulmonary Shunt Flow |
-1.10; -0.30 | — |
| SECONDARY Time to Reach Maximum Drug Concentration in Plasma (Tmax) of Riociguat and Metabolite M1 After Single Dose of Riociguat |
1.75; 1.742; 2.033; 2.042; 11.97; 10.04 | — |
| SECONDARY Half-life Associated With the Terminal Slope (t1/2) of Riociguat and Metabolite M1 After Single Dose of Riociguat |
8.422; 9.541; 12.18; 8.835; NA; 20.57 | — |
| SECONDARY Mean Residence Time (MRT) of Riociguat and Metabolite M1 After Single Dose of Riociguat |
12.92; 13.97; 18.88; 13.37; NA; 34.77 | — |
| 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 |
426.3; 1196; 294.7; 750.3; 200.1; 727.4 | — |
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).
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 105 bpm,
- PaO2 (arterial partial oxygen pressure)/FiO2 (fraction of inspired oxygen) 55 mmHg,
- Severe hepatic insufficiency,
- Severe renal insufficiency.
Data sourced from ClinicalTrials.gov (NCT00640315). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.