Clinical trial NCT00810693: A Study to Evaluate Efficacy and Safety of Oral BAY63-2521 in Patients With Pulmonary Arterial Hypertension (PAH)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pulmonary Hypertension
Keywords: Pulmonary arterial hypertension
PH
Stimulator
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2008-12-18
Enrollment: 445
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility 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.

Primary outcomes:
measure: 6 Minutes Walking Distance (6MWD) - Change From Baseline to Week 12
timeFrame: Baseline and week 12
Secondary outcomes:
measure: Pulmonary Vascular Resistance (PVR) - Change From Baseline to Week 12
timeFrame: Baseline and week 12
measure: N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP) - Change From Baseline to Week 12
timeFrame: Baseline and week 12
measure: World Health Organization (WHO) Functional Class - Change From Baseline to Week 12
timeFrame: Baseline and week 12
measure: Percentage of Participants With Clinical Worsening
timeFrame: At week 12
measure: Borg CR 10 Scale - Change From Baseline to Week 12
timeFrame: Baseline and week 12
measure: EQ-5D Utility Score - Change From Baseline to Week 12
timeFrame: Baseline and week 12
measure: Living With Pulmonary Hypertension (LPH) Questionnaire - Change From Baseline to Week 12
timeFrame: Baseline and week 12
Other outcomes:
Locations:
city: Tucson
country: United States
state: Arizona
city: La Jolla
country: United States
state: California
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Louisville
country: United States
state: Kentucky
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Omaha
country: United States
state: Nebraska
city: New York
country: United States
state: New York
city: Cincinnati
country: United States
state: Ohio
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Fairfield
country: United States
state: Ohio
city: Providence
country: United States
state: Rhode Island
city: Dallas
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Houston
country: United States
state: Texas
city: Capital Federal
country: Argentina
city: Darlinghurst
country: Australia
state: New South Wales
city: New Lambton Heights
country: Australia
state: New South Wales
city: Auchenflower
country: Australia
state: Queensland
city: Herston
country: Australia
state: Queensland
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Prahran
country: Australia
state: Victoria
city: Linz
country: Austria
state: Oberösterreich
city: Innsbruck
country: Austria
city: Wien
country: Austria
city: Bruxelles - Brussel
country: Belgium
city: Leuven
country: Belgium
city: Porto Alegre
country: Brazil
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
state: Sao Paulo
city: São Paulo
country: Brazil
state: Sao Paulo
city: Rio de Janeiro
country: Brazil
city: Calgary
country: Canada
state: Alberta
city: Toronto
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Guangzhou
country: China
state: Guangdong
city: Beijing
country: China
city: Beijing
country: China
city: Shanghai
country: China
city: Shanghai
country: China
city: Praha 2
country: Czechia
city: Aarhus N
country: Denmark
city: Besancon
country: France
city: Brest
country: France
city: GRENOBLE Cedex 09
country: France
city: Lille Cedex
country: France
city: Montpellier
country: France
city: Nice
country: France
city: Pessac
country: France
city: Rouen
country: France
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Gießen
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
state: Niedersachsen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Homburg
country: Germany
state: Saarland
city: Dresden
country: Germany
state: Sachsen
city: Leipzig
country: Germany
state: Sachsen
city: Chaidari
country: Greece
city: Petah Tikva
country: Israel
city: Trieste
country: Italy
state: Friuli-Venezia Giulia
city: Roma
country: Italy
state: Lazio
city: Milano
country: Italy
state: Lombardia
city: Pavia
country: Italy
state: Lombardia
city: Torino
country: Italy
state: Piemonte
city: Nagoya
country: Japan
state: Aichi
city: Yoshida
country: Japan
state: Fukui
city: Kobe
country: Japan
state: Hyogo
city: Toride
country: Japan
state: Ibaraki
city: Tsukuba
country: Japan
state: Ibaraki
city: Kanazawa
country: Japan
state: Ishikawa
city: Sagamihara
country: Japan
state: Kanagawa
city: Sendai
country: Japan
state: Miyagi
city: Tomigusuku
country: Japan
state: Okinawa
city: Bunkyo-ku
country: Japan
state: Tokyo
city: Mitaka
country: Japan
state: Tokyo
city: Ota-ku
country: Japan
state: Tokyo
city: Shinjuku-ku
country: Japan
state: Tokyo
city: Hiroshima
country: Japan
city: Okayama
country: Japan
city: Seoul
country: Korea, Republic of
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Guadalajara
country: Mexico
state: Jalisco
city: Guadalajara
country: Mexico
state: Jalisco
city: Monterrey
country: Mexico
state: Nuevo Leon
city: Culiacan
country: Mexico
state: Sinaloa
city: Mexico D.F.
country: Mexico
city: Querétaro
country: Mexico
city: Christchurch
country: New Zealand
city: Otwock
country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
city: Porto
country: Portugal
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Barcelona
country: Spain
city: Barcelona
country: Spain
city: Sevilla
country: Spain
city: Linköping
country: Sweden
city: Lund
country: Sweden
city: Umeå
country: Sweden
city: Zürich
country: Switzerland
city: Kaohsiung City
country: Taiwan
city: Taipei
country: Taiwan
city: Taipei
country: Taiwan
city: Bangkok
country: Thailand
city: Chiang Mai
country: Thailand
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Cambridge
country: United Kingdom
state: Cambridgeshire
city: Clydebank
country: United Kingdom
state: West Dunbartonshire
city: London
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Archer SL. Riociguat for pulmonary hypertension--a glass half full. N Engl J Med. 2013 Jul 25;369(4):386-8. doi: 10.1056/NEJMe1306684. No abstract available.
citation: Ghofrani HA, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh AM, Langleben D, Kilama MO, Fritsch A, Neuser D, Rubin LJ; PATENT-1 Study Group. Riociguat for the treatment of pulmonary arterial hypertension. N Engl J Med. 2013 Jul 25;369(4):330-40. doi: 10.1056/NEJMoa1209655.
citation: Rosenkranz S, Ghofrani HA, Beghetti M, Ivy D, Frey R, Fritsch A, Weimann G, Saleh S, Apitz C. Riociguat for pulmonary arterial hypertension associated with congenital heart disease. Heart. 2015 Nov;101(22):1792-9. doi: 10.1136/heartjnl-2015-307832. Epub 2015 Jul 1.
citation: Wang C, Jing ZC, Huang YG, Zhou DX, Liu ZH, Meier C, Nikkho S, Curram J, Zhang P, He JG. Riociguat for the treatment of pulmonary hypertension: Chinese subgroup analyses and comparison. Heart Asia. 2016 May 17;8(1):74-82. doi: 10.1136/heartasia-2015-010712. eCollection 2016.
citation: Ghofrani HA, Humbert M, Langleben D, Schermuly R, Stasch JP, Wilkins MR, Klinger JR. Riociguat: Mode of Action and Clinical Development in Pulmonary Hypertension. Chest. 2017 Feb;151(2):468-480. doi: 10.1016/j.chest.2016.05.024. Epub 2016 Jun 2.
citation: Benza RL, Boucly A, Farber HW, Frost AE, Ghofrani HA, Hoeper MM, Lambelet M, Rahner C, Bansilal S, Nikkho S, Meier C, Sitbon O. Change in REVEAL Lite 2 risk score predicts outcomes in patients with pulmonary arterial hypertension in the PATENT study. J Heart Lung Transplant. 2022 Mar;41(3):411-420. doi: 10.1016/j.healun.2021.10.013. Epub 2021 Oct 28.
citation: Benza RL, Farber HW, Frost AE, Ghofrani HA, Corris PA, Lambelet M, Nikkho S, Meier C, Hoeper MM. Application of the REVEAL risk score calculator 2.0 in the CHEST study. Respir Med. 2022 Apr-May;195:106783. doi: 10.1016/j.rmed.2022.106783. Epub 2022 Mar 1.
citation: Benza RL, Ghofrani HA, Grunig E, Hoeper MM, Jansa P, Jing ZC, Kim NH, Langleben D, Simonneau G, Wang C, Busse D, Meier C, Ghio S. Effect of riociguat on right ventricular function in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. J Heart Lung Transplant. 2021 Oct;40(10):1172-1180. doi: 10.1016/j.healun.2021.06.020. Epub 2021 Jul 10.
citation: Humbert M, Coghlan JG, Ghofrani HA, Grimminger F, He JG, Riemekasten G, Vizza CD, Boeckenhoff A, Meier C, de Oliveira Pena J, Denton CP. Riociguat for the treatment of pulmonary arterial hypertension associated with connective tissue disease: results from PATENT-1 and PATENT-2. Ann Rheum Dis. 2017 Feb;76(2):422-426. doi: 10.1136/annrheumdis-2015-209087. Epub 2016 Jul 25.
citation: Saleh S, Becker C, Frey R, Muck W. Population pharmacokinetics and the pharmacokinetic/pharmacodynamic relationship of riociguat in patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. Pulm Circ. 2016 Mar;6(Suppl 1):S86-96. doi: 10.1086/685404.