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A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With CTEPH. (CHEST-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00855465
First received: December 15, 2008
Last updated: October 24, 2014
Last verified: October 2014
  Purpose

The aim of the study is to assess the efficacy and safety of different doses of BAY63-2521, given orally for 16 weeks, in patients with Chronic Thromboembolic Pulmonary Hypertension (CTEPH).


Condition Intervention Phase
Pulmonary Hypertension
Drug: Riociguat (Adempas, BAY63-2521)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Randomized, Double-blind, Placebo-controlled, Multi-centre, Multi-national Study to Evaluate the Efficacy and Safety of Oral BAY63-2521 (1 mg, 1.5 mg, 2 mg, or 2.5 mg Tid) in Patients With Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    6-minute walking distance (6MWD) is a measure for the objective evaluation of a participant's functional exercise capacity.


Secondary Outcome Measures:
  • Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    The pulmonary vascular resistance (PVR) is a calculated hemodynamic parameter. PVR is derived from the directly measured parameters mean pulmonary arterial pressure (PAPmean) and pulmonary capillary wedge pressure (PCWP), divided by the cardiac output (CO). PVR and PAPmean are acquired during a right heart catheterization. CO is a calculated hemodynamic parameter, too. Formula: PVR = 80*(PAPmean - PCWP)/CO

  • N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    N-terminal pro-brain natriuretic peptide (NT-proBNP) levels in the blood are used for screening, diagnosis of acute congestive heart failure (CHF) and may be useful to establish prognosis in heart failure.

  • World Health Organization (WHO) Functional Class - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (Patients with PH but without resulting limitation of physical activity) to class IV (Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right-heart failure.). Changes to a lower WHO functional class resemble improvement; changes to a higher functional class resemble deterioration of PAH.

  • Percentage of Participants With Clinical Worsening [ Time Frame: At week 16 ] [ Designated as safety issue: No ]
    The combined endpoint "time to clinical worsening", made up of the following components, defined by the first occurrence: all-cause mortality; heart/lung transplantation; rescue endarterectomy; first hospitalization due to pulmonary hypertension; start of a new pulmonary hypertension treatment; persistent worsening of 6MWD or WHO functional class due to deterioration of PH.

  • Borg CR 10 Scale - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    The Borg CR10 Scale is a participant reported outcome measure used in clinical diagnosis of e.g. breathlessness and dyspnea. It documents the participant's exertion during a physical test. Low values indicate low levels of exertion; high values indicate more intense exertion reported by the participant. The score ranges from 0 ("Nothing at all") to 10 ("Extremely strong - Maximal").

  • EQ-5D Utility Score - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    EQ-5D utility score is a Quality-of-Life participant reported outcome measure. The utility score is calculated based on five questions concerning problems with mobility, self-care, usual activities, pain/discomfort and anxiety/depression. An increase in the utility score represents an improvement in quality of life. The score ranges from -0.594 (worst answer in all five questions) to 1 (best answer in all five questions).

  • Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    The self-reported Living with Pulmonary Hypertension (LPH) questionnaire is designed to measure the effects of PH and PH-specific treatments on an individual's quality of life. The LPH total score can range from 0 (best) to 105 (worst).


Other Outcome Measures:
  • All Caused Mortality [ Time Frame: At visit 6 (week 16) ] [ Designated as safety issue: Yes ]
    All cause mortality (including cardiovascular mortality) was one component of the composite endpoint "time to clinical worsening".

  • Mean Pulmonary Artery Pressure (PAPmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    Mean pulmonary arterial pressure (PAPmean) is a directly measured hemodynamic parameter. PAPmean is recorded during a right heart catheterization.

  • Cardiac Index (CI) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: No ]
    The cardiac index (CI) is a calculated hemodynamic parameter. CI is derived from the directly measured parameters cardiac output (CO), divided by the body surface area (BSA). BSA is a calculated parameter, using the subject's height and weight in the DuBois formula. Formula: BSA = (W [kg]*0.425)*(H [cm]*0.725)*0.007184 (m^2)

  • Systolic Blood Pressure (SBP) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Systolic systemic arterial blood pressure (SBP) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: 95 - 180 mmHg.

  • Diastolic Blood Pressure (DBP) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Diastolic systemic arterial blood pressure (DBP) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: <= 110 mmHg.

  • Heart Rate (HR) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Heart rate (HR) is a directly non-invasively measured hemodynamic parameter. Range allowed in this study at Visit 0 and/or Visit 1 before randomization: 50 -105 beats per minute (bpm) at rest.

  • Alanine Aminotransferase (ALT) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Alanine Aminotransferase (ALT) is a standard clinical chemistry parameter. Normal range: 0 to 45 U/L.

  • Aspartate Aminotransferase (AST) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Aspartate Aminotransferase (AST) is a standard clinical chemistry parameter. Normal range: 0 to 41 U/L.

  • Alkaline Phosphatase (AP) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Alkaline phosphatase (AP) is a standard clinical chemistry parameter. Normal range: 40 to 129 U/L (males), 35 to 104 U/L (females)

  • Bilirubin - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Bilirubin is a standard clinical chemistry parameter. Normal range: 0.1 to 1.2 mg/dL

  • Creatinine - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Creatinine is a standard clinical chemistry parameter. Normal range: 0.25 to 1.20 mg/dL (males), 0.46 to 1.00 mg/dL (females)

  • Creatinine Clearance - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Creatinine clearance is a standard clinical chemistry parameter. Normal range: 90 to 140 mL/min (males), 80 to 125 mL/min (females)

  • Creatine Kinase (CK) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Creatine Kinase is a standard clinical chemistry parameter. Normal range: 35 to 232 U/L (males), 26 to 145 U/L (females)

  • Erythrocytes (RBC) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Erythrocytes (red blood cells, RBC) is a standard clinical hematology parameter. Normal range: 4.6 to 5.8*10^12 cells/L (males), 4.1 to 5.2*10^12 cells/L (females)

  • Leukocytes (WBC) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Leukocytes (white blood cells, WBC) is a standard clinical hematology parameter. Normal range: 4.0 to 10.7*10^9 cells/L

  • Lymphocytes - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Total lymphocytes is a standard clinical hematology parameter. Normal range: 1.0 to 4.0*10^9 cells/L

  • Neutrophils - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Neutrophils is a standard clinical hematology parameter. Normal range: 1.6 to 7.4*10^9 cells/L

  • Hemoglobin - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Hemoglobin is a standard clinical hematology parameter. Normal range: 13.5 to 17.5 g/dL (males), 12.0 to 16.0 g/dL (females)

  • Hematocrit - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Hematocrit is a standard clinical hematology parameter. Normal range: 40 to 52% (males), 36 to 46% (females)

  • Potassium - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Potassium is a standard clinical chemistry parameter. Normal range: 3.5 to 5.3 mmol/L

  • Urate - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Urate is a standard clinical chemistry parameter. Normal range: 4.0 to 8.5 mg/dL (males, 16-59 years), 3.4 to 8.7 mg/dL (males, >60 years) 2.5 to 7.5 mg/dL (females)

  • Urea (BUN) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Urea (blood urea nitrogen, BUN) is a standard clinical chemistry parameter. Normal range: 4 to 25 mg/dL

  • Cystatin C - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Cystatin C is a biomarker. Normal range: 0.53 to 1.01 ng/mL

  • Triacylglycerol Lipase - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Triacylglycerol lipase is a standard clinical chemistry parameter. Normal range: 7 to 60 U/L

  • Arterial Partial Pressure of Carbon Dioxide (PaCO2) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Arterial partial pressure of carbon dioxide (PaCO2) is performed as part of the capillary or arterial blood gas analysis. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.

  • Arterial Partial Oxygen Pressure (PaO2) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Arterial partial pressure of oxygen (PaO2) is performed as part of the capillary or arterial blood gas analysis. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.

  • Oxygen Saturation (SaO2) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Oxygen saturation (SaO2) is measured as part of the capillary or arterial blood gas analysis. Normal blood oxygen saturation is considered 95-100 percent. If possible, no supplementary oxygen was given during the resting period and while blood samples were drawn.

  • Mean PR Duration (PRmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    PR duration was evaluated as part of the 12-lead electrocardiogram. electrocardiograms (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 Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    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.

  • Mean QT Duration (QTmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    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 QTcB Duration (Bazett's Correction Formula, QTcB) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    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 QTcF Duration (Fridericia's Correction Formula, QTcF) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    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 RR Duration (RRmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    RR 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 Ventricular Rate (VRmean) - Change From Baseline to Week 16 [ Time Frame: Baseline and week 16 ] [ Designated as safety issue: Yes ]
    Ventricular rate 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


Enrollment: 262
Study Start Date: February 2009
Study Completion Date: June 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Riociguat (Adempas, BAY63-2521)_individual dose titration
Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 16 weeks
Drug: Riociguat (Adempas, BAY63-2521)
BAY63-2521: 1 mg tid - 2,5 mg tid orally for 16 weeks.
Placebo Comparator: Placebo
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 16 weeks
Drug: Placebo
Matching Placebo tid orally for 16 weeks

Detailed Description:

Adverse event data will be covered in Adverse events section.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients with CTEPH either inoperable or with persistent or recurrent PH after surgery.

Exclusion Criteria:

  • All types of pulmonary hypertension except subtypes 4.1 and 4.2 of the Venice Clinical Classification of Pulmonary Hypertension.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00855465

  Show 131 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00855465     History of Changes
Other Study ID Numbers: 11348, 2007-000072-16
Study First Received: December 15, 2008
Results First Received: November 4, 2013
Last Updated: October 24, 2014
Health Authority: Argentina: National Administration of Drugs, Foods and Medical Technology
Australia: Department of Health
Austria: Ministry of Labor, Health and Social Affairs
Belgium: Ministry of Social Affairs, Public Health and the Environment
Brazil: Ministry of Health
Canada: Health Protection Branch
China: Ministry of Health- State Food and Drug Administration
Czech Republic: Ministry of Health
Denmark: Danish Medicines Agency
France: Ministry of Health
Germany: Federal Institute for Drugs and Medical Devices
Israel: Ministry of Health
Italy: Ministry of Health
Japan: Ministry of Health and Welfare
Korea, Republic of: Food and Drug Administration
Mexico: Ministry of Health
Netherlands: Medicines Evaluation Board
Poland: Ministry of Health and Social Security- Drug Institute
Portugal: Ministry of Health
Russia: Ministry of Health
Slovakia: State Institute for Drug Control
Spain: Ministry of Health and Consumption
Switzerland: Federal Office of Public Health
Taiwan: Department of Health
Turkey: Ministry of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration

Keywords provided by Bayer:
Chronic thromboembolic pulmonary hypertension
PH
soluble Guanylate Cyclase Stimulator
sGC

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 23, 2014