Skip to main content
OpenTrials
Completed

NCT Number: NCT00640315

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

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).

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Hypertension, Pulmonary Cardiovascular Diseases Chronic Disease Disease Attributes Hypertension Lung Diseases Lung Diseases, Obstructive Pathologic Processes Pathological Conditions, Signs and Symptoms Pulmonary Disease, Chronic Obstructive Respiratory Tract Diseases Vascular Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Heidelberg, Baden-Wurttemberg, Germany

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Riociguat (Adempas, BAY63-2521) 1.0 mg

Drug

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).

Riociguat (Adempas, BAY63-2521) 2.5 mg

Drug

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).

Primary outcomes

  1. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Pulmonary Artery Pressure (PAPmean)

    Time frame: From baseline up to 4 hours after administration

    PAPmean was reported during right heart catheterization

  2. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance (PVR)

    Time frame: From baseline up to 4 hours after administration

    PVR was calculated according to the formula PVR = 80*(PAPmean - pulmonary capillary wedge pressure)/cardiac output

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

Secondary outcomes

  1. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Right Atrial Pressure (RAPmean)

    Time frame: From baseline up to 4 hours after administration

    RAPmean was reported during right heart catheterization

  2. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Pulmonary Artery Pressure (PAPsyst)

    Time frame: From baseline up to 4 hours after administration

    PAPsyst was acquired during right heart catheterization

  3. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Pulmonary Artery Pressure (PAPdiast)

    Time frame: From baseline up to 4 hours after administration

    PAPdiast was acquired during right heart catheterization

  4. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Capillary Wedge Pressure (PCWP)

    Time frame: From baseline up to 4 hours after administration

    PCWP was acquired during right heart catheterization

  5. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Heart Rate (HR)

    Time frame: From baseline up to 4 hours after administration

    HR was acquired during right heart catheterization

  6. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systolic Blood Pressure (SBP)

    Time frame: From baseline up to 4 hours after administration

    Systolic arterial blood pressure was acquired during right heart catheterization.

  7. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Diastolic Blood Pressure (DBP)

    Time frame: From baseline up to 4 hours after administration

    Diastolic arterial blood pressure was acquired during right heart catheterization.

  8. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Mean Arterial Pressure (MAP)

    Time frame: From baseline up to 4 hours after administration

    MAP was acquired during right heart catheterization

  9. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Output (CO)

    Time frame: From baseline up to 4 hours after administration

    CO was measured in triplicate by the thermodilution technique

  10. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Pulmonary Vascular Resistance Index (PVRI)

    Time frame: From baseline up to 4 hours after administration

    PVRI was calculated as PVRI = (80*(PAPmean - PCWP)/CO)*body surface area

  11. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance (SVR)

    Time frame: From baseline up to 4 hours after administration

    SVR was calculated as SVR = 80*(MAP-RAPmean)/CO

  12. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Systemic Vascular Resistance Index (SVRI)

    Time frame: From baseline up to 4 hours after administration

    SVRI was calculated as SVRI = (80*(MAP - RAPmean)/CO)*body surface area

  13. Swan-Ganz Hemodynamics - Maximal Change From Baseline at Day 1 of Cardiac Index

    Time frame: From baseline up to 4 hours after administration

    Cardiac index was calculated as cardiac index = CO / body surface area.

  14. Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Oxygen Pressure (PaO2)

    Time frame: 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".

  15. Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Partial Pressure of Carbon Dioxide (PaCO2)

    Time frame: 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".

  16. Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Pressure (PvO2)

    Time frame: Baseline and 2 hours post dose

    Percent change was calculated as "100%*(value post dose - value at baseline)/ value at baseline".

  17. Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Arterial Oxygen Saturation (SaO2)

    Time frame: 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".

  18. Blood Gas Analysis - Percentage Change From Baseline at 2 Hours Post Dose of Venous Oxygen Saturation (SvO2)

    Time frame: Baseline and 2 hours post dose

    Percent change was calculated as "100%*(value post dose - value at baseline)/ value at baseline".

  19. 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

  20. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FEV1

    Time frame: Baseline and 2 hours post dose

  21. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Vital Capacity (FVC)

    Time frame: Baseline and 2 hours post dose

  22. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted FVC

    Time frame: Baseline and 2 hours post dose

  23. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of FEV1/FVC

    Time frame: Baseline and 2 hours post dose

  24. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Lung Capacity (TLC)

    Time frame: Baseline and 2 hours post dose

  25. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted TLC

    Time frame: Baseline and 2 hours post dose

    The percent of predicted TLC was provided by investigator at site.

  26. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Residual Volume (RV)

    Time frame: Baseline and 2 hours post dose

  27. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted RV

    Time frame: Baseline and 2 hours post dose

  28. 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

  29. 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

  30. 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

  31. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Total Airway Resistance (Raw)

    Time frame: Baseline and 2 hours post dose

  32. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Vital Capacity (VC)

    Time frame: Baseline and 2 hours post dose

  33. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Percent of Predicted VC

    Time frame: Baseline and 2 hours post dose

  34. 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

  35. 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

  36. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Specific Diffusing Capacity

    Time frame: Baseline and 2 hours post dose

  37. 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

  38. 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

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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

  44. 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

  45. 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

  46. 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

  47. 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

  48. 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

Other outcomes

  1. Mean PR Duration (PRmean) - Change From Baseline to Day 3

    Time frame: 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.

  2. Mean QRS Duration (QRSmean) - Change From Baseline to Day 3

    Time frame: 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.

  3. Mean QT Duration (QTmean) - Change From Baseline to Day 3

    Time frame: 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.

  4. Mean QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Day 3

    Time frame: 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.

  5. Mean QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Day 3

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study 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

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Mar 21, 2008
Registry last updated
Dec 28, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.