A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With Pulmonary Arterial Hypertension (PAH) (PATENT-1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00810693
First received: December 17, 2008
Last updated: January 24, 2014
Last verified: January 2014
  Purpose

The aim of the study is to assess the efficacy and safety of different doses of BAY63-2521 given orally for 12 weeks, in patients with symptomatic Pulmonary Arterial Hypertension (PAH).


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 Symptomatic Pulmonary Arterial Hypertension (PAH)

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 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    6-minute walking distance (6MWD) is a measure for the objective evaluation of a patient's functional exercise capacity.


Secondary Outcome Measures:
  • Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12 [ Time Frame: Baseline and week 12 ] [ 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 12 [ Time Frame: Baseline and week 12 ] [ 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 12 [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    The WHO functional assessment of pulmonary arterial hypertension ranged from functional class I (participants with PH but without resulting limitation of physical activity) to class IV (participants with PH with inability to carry out any physical activity without symptoms. These participants 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 12 ] [ 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; atrial septostomy; 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 12 [ Time Frame: Baseline and week 12 ] [ 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 12 [ Time Frame: Baseline and week 12 ] [ 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 12 [ Time Frame: Baseline and week 12 ] [ 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).


Enrollment: 445
Study Start Date: December 2008
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Riociguat (Adempas, BAY63-2521) up to 2.5 mg_IDT
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 12 weeks
Drug: Riociguat (Adempas, BAY63-2521)
BAY63-2521: 1mg tid - 2.5mg tid orally for 12 weeks
Experimental: Riociguat (Adempas, BAY63-2521) up to 1.5 mg_IDT
Participants received Riociguat orally as a film-coated tablet up to 1.5mg three times daily (tid) (titration between 1.0 mg and 1.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks
Drug: Riociguat (Adempas, BAY63-2521)
BAY63-2521: 1.5mg tid orally for 12 weeks
Placebo Comparator: Placebo
Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks
Drug: Placebo
Matching Placebo tid orally for 12 weeks

  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 symptomatic PAH (Idiopathic, Familial, Associated PAH due to connective tissue disease, congenital heart disease, portal hypertension with liver cirrhosis, or due to anorexigen or amphetamine use)
  • Treatment naive patients and patients pre-treated with an Endothelin Antagonist or a Prostacyclinanalogue (except I.V.).

Exclusion Criteria:

  • All types of pulmonary hypertension except subtypes of Venice Group I specified in the inclusion criteria, severe COPD (chronic obstructive pulmonary disease), uncontrolled arterial hypertension, left heart failure.
  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: NCT00810693

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States, 35233
United States, Arizona
Tuscon, Arizona, United States, 85724
United States, California
Fresno, California, United States, 93721
La Jolla, California, United States, 92037
Los Angeles, California, United States, 90073
Sacramento, California, United States, 95817
Torrance, California, United States, 90502
United States, Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Gainesville, Florida, United States, 32610
Miami, Florida, United States, 33136
Sarasota, Florida, United States, 34239
Weston, Florida, United States, 33331
United States, Georgia
Atlanta, Georgia, United States, 30342
Decatur, Georgia, United States, 30030
United States, Iowa
Iowa City, Iowa, United States, 52242
United States, Kentucky
Louisville, Kentucky, United States, 40202
United States, Maine
Portland, Maine, United States, 04102
United States, Maryland
Baltimore, Maryland, United States, 21205
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Boston, Massachusetts, United States, 02115
Boston, Massachusetts, United States, 02111
Boston, Massachusetts, United States, 02114
United States, Michigan
Ann Arbor, Michigan, United States, 48109
United States, Minnesota
Rochester, Minnesota, United States, 55905
United States, Missouri
St. Louis, Missouri, United States, 63110
United States, Nebraska
Omaha, Nebraska, United States, 68131
United States, New Jersey
Newark, New Jersey, United States, 07103
United States, New York
New York, New York, United States, 10032
Rochester, New York, United States, 14642
United States, Ohio
Cincinnati, Ohio, United States, 45219
Cleveland, Ohio, United States, 44106
Cleveland, Ohio, United States, 44195
Columbus, Ohio, United States, 43221
Fairfield, Ohio, United States, 45014
United States, Pennsylvania
Pittsburgh, Pennsylvania, United States, 15212
United States, Rhode Island
Providence, Rhode Island, United States, 02903
United States, Texas
Dallas, Texas, United States, 75390
El Paso, Texas, United States, 79902
Houston, Texas, United States, 77030
Argentina
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1181ACH
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1093AAS
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1120AAF
Buenos Aires, Ciudad Auton. de Buenos Aires, Argentina, C1039AAO
Capital Federal, Argentina
Vicente López, Argentina, 1638
Australia, New South Wales
Darlinghurst, New South Wales, Australia, 2010
New Lambton Heights, New South Wales, Australia, 2305
Australia, Queensland
Auchenflower, Queensland, Australia, 4066
Chermside, Queensland, Australia, 4032
Australia, Tasmania
Hobart, Tasmania, Australia, 7000
Australia, Victoria
Heidelberg, Victoria, Australia, 3084
Prahran, Victoria, Australia, 3181
Austria
Linz, Oberösterreich, Austria, 4010
Innsbruck, Austria, 6020
Wien, Austria, 1090
Belgium
Bruxelles - Brussel, Belgium, 1070
Leuven, Belgium, 3000
Brazil
Porto Alegre, Rio Grande do Sul, Brazil, 90020 090
São Paulo, Sao Paulo, Brazil, 04024-002
São Paulo, Sao Paulo, Brazil, 04012 180
Rio de Janeiro, Brazil, 21941-900
São Paulo, Brazil, 05403-000
Canada, Alberta
Calgary, Alberta, Canada, T1Y 6J4
Canada, Ontario
Hamilton, Ontario, Canada, L8L 2X2
Toronto, Ontario, Canada, M5G 2N2
Canada, Quebec
Montreal, Quebec, Canada, H3T 1E2
Canada
Quebec, Canada, G1V 4G5
China, Guangdong
Guangzhou, Guangdong, China, 510100
China
Beijing, China, 100037
Beijing, China, 100020
Shanghai, China, 200032
Shanghai, China, 200433
Czech Republic
Praha 2, Czech Republic, 12800
Denmark
Aarhus N, Denmark, 8200
France
Besancon, France, 25030
Brest, France, F-29609
Bron, France, 69500
Caen, France, 14033
Clamart Cedex, France, 92141
GRENOBLE Cedex 09, France, 38043
Lille Cedex, France, 59037
Marseille, France, 13385
Montpellier, France, 34059
Nice, France, 06200
Pessac, France, 33604
Rouen, France, 76031
Tours, France, 37000
Germany
Heidelberg, Baden-Württemberg, Germany, 69126
München, Bayern, Germany, 81377
Gießen, Hessen, Germany, 35392
Greifswald, Mecklenburg-Vorpommern, Germany, 17475
Hannover, Niedersachsen, Germany, 30625
Köln, Nordrhein-Westfalen, Germany, 50924
Homburg, Saarland, Germany, 66421
Dresden, Sachsen, Germany, 01307
Leipzig, Sachsen, Germany, 04103
Greece
Haidari, Greece, 124 62
Kallithea / Athens, Greece, 17674
Ireland
Dublin, Ireland
Israel
Jerusalem, Israel, 91120
Petach Tikva, Israel, 4941492
Tel Aviv, Israel, 6423906
Italy
Orbassano, Torino, Italy, 10043
Bologna, Italy, 40138
Milano, Italy, 20123
Pavia, Italy, 27100
Roma, Italy, 00161
Trieste, Italy, 34149
Japan
Nagoya, Aichi, Japan, 467-8602
Toyoake, Aichi, Japan, 470-1192
Yoshida, Fukui, Japan, 910-1193
Asahikwa, Hokkaido, Japan, 078-8510
Kobe, Hyogo, Japan, 650-0017
Toride, Ibaraki, Japan, 302-0022
Tsukuba, Ibaraki, Japan, 305-8576
Kanazawa, Ishikawa, Japan, 920-8641
Sagamihara, Kanagawa, Japan, 252-0375
Sendai, Miyagi, Japan, 980-8574
Tomigusuku, Okinawa, Japan, 901-0243
Hamamatsu, Shizuoka, Japan, 430-0929
Bunkyo-ku, Tokyo, Japan, 113-8655
Mitaka, Tokyo, Japan, 181-8611
Ota-ku, Tokyo, Japan, 143-8541
Shinjuku-ku, Tokyo, Japan, 160-8582
Fukuoka, Japan, 812-8582
Hiroshima, Japan, 734-8551
Okayama, Japan, 701-1192
Tokushima, Japan, 770-8503
Korea, Republic of
Seoul, Seoul Teugbyeolsi, Korea, Republic of, 110-744
Seoul, Korea, Republic of, 120-752
Seoul, Korea, Republic of, 135-710
Seoul, Korea, Republic of, 138-736
Mexico
Guadalajara, Jalisco, Mexico, 44670
Guadalajara, Jalisco, Mexico, 44280
Monterrey, Nuevo Leon, Mexico, 64020
Culiacan, Sinaloa, Mexico, 80020
Mexico D.F., Mexico, 14080
Querétaro, Mexico, 38000
Netherlands
Amsterdam, Netherlands, 1081 HV
Rotterdam, Netherlands, 3015 CE
New Zealand
Christchurch, New Zealand, 8011
Poland
Krakow, Poland, 31-202
Otwock, Poland, 05-400
Portugal
Almada, Portugal, 2801-951
Coimbra, Portugal, 3000-075
Lisboa, Portugal, 1169-024
Lisboa, Portugal, 1649-035
Porto, Portugal, 4099-001
Russian Federation
Moscow, Russian Federation, 121552
St. Petersburg, Russian Federation, 197341
Singapore
Singapore, Singapore, 168752
Singapore, Singapore, 119228
Spain
Barcelona, Spain, 08036
Barcelona, Spain, 08035
Madrid, Spain, 28041
Sevilla, Spain, 41013
Sweden
Linköping, Sweden, 581 85
Lund, Sweden, 221 85
Umeå, Sweden, 901 85
Switzerland
Zürich, Switzerland, 8091
Taiwan
Kaoshiung, Taiwan, 81346
Taichung, Taiwan, 40705
Taipei, Taiwan, 11217
Taipei, Taiwan, 10016
Thailand
Bangkok, Thailand, 10400
Bangkok, Thailand, 10330
Chiang Mai, Thailand, 50200
Turkey
Ankara, Turkey
Istanbul, Turkey, 34304
Istanbul, Turkey, 34098
Izmir, Turkey, 35-100
United Kingdom
Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
Clydebank, West Dunbartonshire, United Kingdom, G81 4DY
London, United Kingdom, W12 0HS
London, United Kingdom, NW3 2QG
Newcastle, United Kingdom, NE7 7DN
Sheffield, United Kingdom, S10 2JF
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00810693     History of Changes
Other Study ID Numbers: 12934, 2008-003482-68
Study First Received: December 17, 2008
Results First Received: November 5, 2013
Last Updated: January 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
Greece: Ministry of Health and Welfare
Ireland: Irisch Medicines Board
Israel: Ministry of Health
Italy: Ministry of Health
Japan: Ministry of Health and Welfare
Korea: Food and Drug Administration
Mexico: Ministry of Health
Netherlands: Medicines Evaluetion Board
New Zealand: Medicines and Medical Devices Safety Authority
Poland: Ministry of Health and Social Security - Drug Institute
Portugal: Ministry of Health
Russia: Ministry of Health
Singapore: Ministry of Health
Spain: Ministry of Health and Consumption
Sweden: Medical Products Agency
Switzerland: Federal Office of Public Health
Thailand: Ministry 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:
Pulmonary arterial hypertension
PH
Stimulator

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

ClinicalTrials.gov processed this record on September 30, 2014