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Hypertension, PulmonaryPhase 1NCT00640315

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

A Phase 1 study testing Riociguat (Adempas, BAY63-2521) 1.0 mg and Riociguat (Adempas, BAY63-2521) 2.5 mg in people with Hypertension, Pulmonary and Pulmonary Disease, Chronic Obstructive, run by Bayer at 7 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Riociguat (Adempas, BAY63-2521) 1.0 mg and Riociguat (Adempas, BAY63-2521) 2.5 mg
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
7 sitesGermany
Study dates
Aug 2008to Sep 2009
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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,
Show all 13Show fewer
  • 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.

Trial locations and contacts

7 sites in 1 country.

7 sites in 1 country

Germany7 sites

  • Study site

    Bad Nauheim, Hesse, 61231

  • Study site

    Dresden, Saxony, 01307

  • Study site

    Giessen, Hesse, 35392

  • Study site

    Greifswald, Mecklenburg-Vorpommern, 17475

  • Study site

    Heidelberg, Baden-Wurttemberg, 69126

  • Study site

    Löwenstein, Baden-Wurttemberg, 74245

  • Study site

    München, Bavaria, 81377

Other trials in Germany

About this study

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

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).

Read the 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.

Being tested
Riociguat (Adempas, BAY63-2521) 1.0 mg, Riociguat (Adempas, BAY63-2521) 2.5 mg
Keywords
Chronic obstructive pulmonary disease, COPD, Pulmonary hypertension
Medical subject headings
Hypertension, Pulmonary, Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Riociguat (Adempas, BAY63-2521) 1.0 mgDrug

    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 mgDrug

    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).

Study groups in NCT00640315
Study groupRoleWhat they receive
Riociguat (Adempas, BAY63-2521) 1.0 mgExperimentalParticipants received two single oral doses of 1.0 mg riociguat on study day 1 and study day 3.
Receives: Drug: Riociguat (Adempas, BAY63-2521) 1.0 mg
Riociguat (Adempas, BAY63-2521) 2.5 mgExperimentalParticipants received two single oral doses of 2.5 mg riociguat on study day 1 and study day 3.
Receives: Drug: Riociguat (Adempas, BAY63-2521) 2.5 mg

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    PAPmean was reported during right heart catheterization

    Measured: From baseline up to 4 hours after administration

  2. 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

    Measured: From baseline up to 4 hours after administration

  3. Area Under the Plasma Concentration Versus Time Curve From Zero to Infinity (AUC) of Riociguat and Metabolite M1 After Single Dose of Riociguat

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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 (48)

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

    RAPmean was reported during right heart catheterization

    Measured: From baseline up to 4 hours after administration

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

    PAPsyst was acquired during right heart catheterization

    Measured: From baseline up to 4 hours after administration

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

    PAPdiast was acquired during right heart catheterization

    Measured: From baseline up to 4 hours after administration

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

    PCWP was acquired during right heart catheterization

    Measured: From baseline up to 4 hours after administration

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

    HR was acquired during right heart catheterization

    Measured: From baseline up to 4 hours after administration

  6. 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.

    Measured: From baseline up to 4 hours after administration

  7. 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.

    Measured: From baseline up to 4 hours after administration

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

    MAP was acquired during right heart catheterization

    Measured: From baseline up to 4 hours after administration

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

    CO was measured in triplicate by the thermodilution technique

    Measured: From baseline up to 4 hours after administration

  10. 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

    Measured: From baseline up to 4 hours after administration

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

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

    Measured: From baseline up to 4 hours after administration

  12. 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

    Measured: From baseline up to 4 hours after administration

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

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

    Measured: From baseline up to 4 hours after administration

  14. 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".

    Measured: Baseline and 2 hours post dose

  15. 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".

    Measured: Baseline and 2 hours post dose

  16. 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".

    Measured: Baseline and 2 hours post dose

  17. 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".

    Measured: Baseline and 2 hours post dose

  18. 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".

    Measured: Baseline and 2 hours post dose

  19. Lung Function - Percentage Change From Baseline at 2 Hours Post Dose of Forced Expiratory Volume in 1 Second (FEV1)

    Measured: Baseline and 2 hours post dose

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

    Measured: Baseline and 2 hours post dose

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

    Measured: Baseline and 2 hours post dose

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

    Measured: Baseline and 2 hours post dose

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

    Measured: Baseline and 2 hours post dose

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

    Measured: Baseline and 2 hours post dose

  25. 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.

    Measured: Baseline and 2 hours post dose

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

    Measured: Baseline and 2 hours post dose

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

    Measured: 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)

    Measured: 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)

    Measured: 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)

    Measured: Baseline and 2 hours post dose

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

    Measured: Baseline and 2 hours post dose

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

    Measured: Baseline and 2 hours post dose

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

    Measured: 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)

    Measured: 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)

    Measured: Baseline and 2 hours post dose

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

    Measured: 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)

    Measured: 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)

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Mar 2008 (estimated)
  2. Study startAug 2008
  3. Primary completionSep 2009
  4. Study completionSep 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00640315
Sponsor's protocol ID
12915
Other IDs
2007-003919-31
Status last verified
Nov 2016
First submitted
29 Feb 2008
Last updated
28 Dec 2016
Data monitoring committee
No

Publications

  • H.-A. Ghofrani, G. Staehler, E. Gruenig, M. Halank, V. Mitrovic, S. Unger, W. Mueck, R. Frey, J. Behr. The Effect Of The Soluble Guanylate Cyclase Stimulator Riociguat On Hemodynamics In Patients With Pulmonary Hypertension Due To Chronic Obstructive Pulmonary Disease. D96 CLINICAL TRIALS AND OUTCOMES IN PULMONARY HYPERTENSION.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Riociguat (Adempas, BAY63-2521) 1.0 mg and Riociguat (Adempas, BAY63-2521) 2.5 mg in people with Hypertension, Pulmonary and Pulmonary Disease, Chronic Obstructive, run by Bayer at 7 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Dec 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Feb 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00640315, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Dec 2016.

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