Clinical trial NCT00863681: BAY63-2521:Long-term Extension Study in Patients With Pulmonary Arterial Hypertension
Official title: Long-term Extension, Multicentre, Multi-national Study to Evaluate the Safety and Tolerability of Oral BAY63-2521 (1mg,1.5 mg, 2.0 mg, 2.5 mg Tid) in Patients With Symptomatic Pulmonary Arterial Hypertension (PAH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension, Pulmonary
Keywords: Pulmonary arterial hypertension
PH
Stimulator
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2009-03-18
Enrollment: 396
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Patients who have completed the 12 weeks treatment of the PATENT-1 trial (study number 12934) will be asked to participate in this long term extension study with BAY63-2521.


Eligibility criteria: Inclusion Criteria:

* Patients who have completed 12 weeks of treatment in the double blind trial PATENT 1

Exclusion Criteria:

* Patients who have an ongoing serious adverse event from PATENT 1 that is assessed as related to BAY63-2521 are not allowed to participate in the extension trial.

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events (TEAE)
timeFrame: From administration of first dose of study medication in PATENT-2 up to 2 days after end of treatment with study medication, up to 10 years and 5 months.
measure: Number of Participant With Death
timeFrame: From baseline to end of safety follow-up visit, up to 10 years and 6 months (1 month more than End of study visit)
Secondary outcomes:
measure: Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Hematology and Coagulation
timeFrame: From baseline to termination visit, up to 10 years
measure: Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Hematology and Coagulation
timeFrame: From baseline to termination visit, up to 10 years
measure: Percentage of Participants With Treatment-emergent High Laboratory Abnormalities in Clinical Chemistry
timeFrame: From baseline to termination visit, up to 10 years
measure: Percentage of Participants With Treatment-emergent Low Laboratory Abnormalities in Clinical Chemistry
timeFrame: From baseline to termination visit, up to 10 years
Other outcomes:
measure: Change of Systolic Blood Pressure (SBP)
timeFrame: From baseline to termination visit, up to 10 years
measure: Change of Diastolic Blood Pressure (DBP)
timeFrame: From baseline to termination visit, up to 10 years
measure: Change of Heart Rate
timeFrame: From baseline to termination visit, up to 10 years
measure: Change of Weight
timeFrame: From baseline to termination visit, up to 10 years
measure: Change of Oxygen Saturation (SaO2)
timeFrame: From baseline to termination visit, up to 10 years
measure: Change of Arterial Partial Oxygen Pressure (PaO2)
timeFrame: From baseline to termination visit, up to 10 years
measure: Change of Arterial Partial Pressure of Carbon Dioxide (PaCO2)
timeFrame: From baseline to termination visit, up to 10 years
measure: Change of RR Duration From Electrocardiogram (ECG)
timeFrame: From baseline to Month 48
measure: Change of PR Duration From ECG
timeFrame: From baseline to Month 48
measure: Change of QRS Duration From ECG
timeFrame: From baseline to Month 48
measure: Change of QT Duration in ECG
timeFrame: From baseline to Month 48
measure: Change in Six-minute Walking Distance (6MWD) Test
timeFrame: From baseline to End of study visit, up to 10 years and 5 months.
measure: Change in Pulmonary Vascular Resistance (PVR)
timeFrame: From baseline to Termination visit, up to 10 years 5 months
measure: Change in N-terminal Prohormone of Brain Natriuretic Peptide (NT-proBNP)
timeFrame: From baseline to End of study visit, up to 10 year and 5 months
measure: Change in World Health Organization (WHO) Functional Class
timeFrame: From baseline to End of study visit, up to 10 years and 5 months.
measure: Number of Participants With Clinical Worsening
timeFrame: From baseline to End of study visit, up to 10 years and 5 months.
measure: Incidence of Clinical Worsening Events Per 100 Person Years
timeFrame: From baseline to End of study visit, up to 10 years and 5 months.
measure: Change From Baseline in Borg CR 10 Scale
timeFrame: From baseline to Week 12
measure: Change in Score of EQ-5D Questionnaire
timeFrame: From baseline to End of study visit, up to 10 years and 5 months.
measure: Change in Score of Living With Pulmonary Hypertension (LPH) Questionnaire
timeFrame: From baseline to End of study visit, up to 10 years and 5 months.
Locations:
city: Los Angeles
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Boston
country: United States
state: Massachusetts
city: Boston
country: United States
state: Massachusetts
city: Omaha
country: United States
state: Nebraska
city: Cleveland
country: United States
state: Ohio
city: Columbus
country: United States
state: Ohio
city: Fairfield
country: United States
state: Ohio
city: Dallas
country: United States
state: Texas
city: El Paso
country: United States
state: Texas
city: Capital Federal
country: Argentina
city: Darlinghurst
country: Australia
state: New South Wales
city: Auchenflower
country: Australia
state: Queensland
city: Herston
country: Australia
state: Queensland
city: Hobart
country: Australia
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: 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: 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: 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: Nagoya
country: Japan
state: Aichi
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: 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
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Guadalajara
country: Mexico
facility: Antiguo Hospital Civil de Guadalajara "Fray Antonio Alcalde"
state: Jalisco
city: Guadalajara
country: Mexico
facility: Pulmocritic
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: Otwock
country: Poland
city: Coimbra
country: Portugal
city: Lisboa
country: Portugal
city: Lisboa
country: Portugal
facility: Centro Hospitalar de Lisboa Norte - Hospital Santa Maria
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Singapore
country: Singapore
city: Singapore
country: Singapore
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
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
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: Ghofrani HA, Grimminger F, Grunig E, Huang Y, Jansa P, Jing ZC, Kilpatrick D, Langleben D, Rosenkranz S, Menezes F, Fritsch A, Nikkho S, Humbert M. Predictors of long-term outcomes in patients treated with riociguat for pulmonary arterial hypertension: data from the PATENT-2 open-label, randomised, long-term extension trial. Lancet Respir Med. 2016 May;4(5):361-71. doi: 10.1016/S2213-2600(16)30019-4. Epub 2016 Apr 8.
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, 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.
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: Rubin LJ, Galie N, Grimminger F, Grunig E, Humbert M, Jing ZC, Keogh A, Langleben D, Fritsch A, Menezes F, Davie N, Ghofrani HA. Riociguat for the treatment of pulmonary arterial hypertension: a long-term extension study (PATENT-2). Eur Respir J. 2015 May;45(5):1303-13. doi: 10.1183/09031936.00090614. Epub 2015 Jan 22.
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.