Clinical trial NCT02007629: Riociguat Clinical Effects Studied in Patients With Insufficient Treatment Response to Phosphodiesterase-5 Inhibitor
Official title: An Open-label, International, Multicenter, Single-arm, Uncontrolled, Phase IIIb Study of Riociguat in Patients With Pulmonary Arterial Hypertension (PAH) Who Demonstrate an Insufficient Response to Treatment With Phosphodiesterase-5 Inhibitors (PDE-5i)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hypertension, Pulmonary
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2013-12-11
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: BAY63-2521 Riociguat leads to the relaxation of smooth muscle cells in pulmonary arteria and may also inhibit abnormal remodeling of lung blood vessels. In patients with pulmonary arterial hypertension Riociguat showed to reduce the pulmonary blood pressure and improved the right heart function without unacceptable side effects. Here dose of Riociguat will be adjusted over 8 weeks then a Maintenance Phase of 16 weeks follows. Patients with Pulmonary Arterial Hypertension treated with stable doses of Phosphodiesterase Type-5 Inhibitors (Eg Sildenafil, Tadalafil) not appropriately responding to therapy will be included. Based on previous evidence and on the different modes of action an improvement of exercise capacity, heart function and quality of life may be expected if PDE5i treatment is transitioned to riociguat.

Where Riociguat is pending market approval or reimbursement once the treatment phase is completed drug can be made available for another 18 months (Extended Drug Supply Phase - EDSP) under study conditions. Patients may also transition at the end of the maintenance period or any time during the EDSP to any program that is intended to provide riociguat until drug approval/reimbursement, e.g. a long-term extension study, compassionate use or named patient program. Study termination is also possible at any time.


Eligibility criteria: Inclusion Criteria:

* Male or female patients (18 -75 years of age) with idiopathic, familial, drug/toxin induced and associated PAH due to congenital heart disease (Group I / Dana Point Classification of PH) demonstrating insufficient response to treatment with PDE-5i for at least 3 months
* Patients with and without endothelin receptor antagonist (ERA) therapy
* World Health Organization Functional Class (WHO FC) III at screening
* 6-minute walking distance (6MWD) of 165-440 m
* Cardiac index \<3.0 L/min/m\*2.

Exclusion Criteria:

* All types of PH except subtypes of Dana Point Group I specified in the inclusion criteria
* Evidence of clinically significant restrictive or obstructive parenchymal lung diseases
* Diffusing capacity of the lung for carbon monoxide (DLCO) \<30% predicted
* History or active state of serious hemoptysis / pulmonary hemorrhage including those managed by bronchial artery embolization
* Patients unable to perform a valid 6MWD test
* Pregnant women (i.e. positive pregnancy test or other signs of pregnancy), or breast feeding women, or women with childbearing potential not using a combination of 2 effective methods of birth control, for example a combination of condoms with a safe and highly effective contraception method (prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device) or a double barrier method is used throughout the study.

Primary outcomes:
measure: Change from baseline in 6 Minute Walking Distance (6MWD)
timeFrame: Baseline, Week 12 and Week 24
Secondary outcomes:
Other outcomes:
measure: Change From Baseline in Cardiac Index
timeFrame: Baseline, Week 24
measure: Change From Pre-treatment in N-Terminal Pro-Brain Natriuretic Peptide (NTproBNP)
timeFrame: Baseline, Week 12 and Week 24
measure: Change From Baseline in World Health Organization Functional Class (WHO FC)
timeFrame: Baseline, Week 12 and Week 24
measure: Percentage of Subjects With Clinical Worsening
timeFrame: Baseline to Week 24
measure: Change From Baseline in European Quality of life (Qol)-Group (EQ)-5D Questionnaire
timeFrame: Baseline, Week 12 and Week 24
measure: Change from pre-treatment of 6MWD
timeFrame: Baseline, Week 12 and Week 24
measure: Percentage of Subjects Without Clinical Worsening who Achieve at Least WHO FC II and an Improvement in 6 MWD of Greater Than or Equal to (>=) 30 meters
timeFrame: Baseline, Week 12 and Week 24
Locations:
city: La Jolla
country: United States
state: California
city: Sacramento
country: United States
state: California
city: Iowa City
country: United States
state: Iowa
city: Boston
country: United States
state: Massachusetts
city: Saint Louis
country: United States
state: Missouri
city: Pittsburgh
country: United States
state: Pennsylvania
city: Providence
country: United States
state: Rhode Island
city: Bruxelles - Brussel
country: Belgium
city: Leuven
country: Belgium
city: Montreal
country: Canada
state: Quebec
city: Praha 2
country: Czechia
city: GRENOBLE Cedex 09
country: France
city: Le Kremlin Bicetre Cedex
country: France
city: Marseille
country: France
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Regensburg
country: Germany
state: Bayern
city: Hannover
country: Germany
state: Niedersachsen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Dresden
country: Germany
state: Sachsen
city: Leipzig
country: Germany
state: Sachsen
city: Roma
country: Italy
state: Lazio
city: Pavia
country: Italy
state: Lombardia
city: Zürich
country: Switzerland
city: Newcastle Upon Tyne
country: United Kingdom
state: Tyne And Wear
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: Hoeper MM, Klinger JR, Benza RL, Simonneau G, Langleben D, Naeije R, Corris PA. Rationale and study design of RESPITE: An open-label, phase 3b study of riociguat in patients with pulmonary arterial hypertension who demonstrate an insufficient response to treatment with phosphodiesterase-5 inhibitors. Respir Med. 2017 Jan;122 Suppl 1:S18-S22. doi: 10.1016/j.rmed.2016.11.001. Epub 2016 Nov 5.
citation: Hoeper MM, Simonneau G, Corris PA, Ghofrani HA, Klinger JR, Langleben D, Naeije R, Jansa P, Rosenkranz S, Scelsi L, Grunig E, Vizza CD, Chang M, Colorado P, Meier C, Busse D, Benza RL. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Eur Respir J. 2017 Sep 9;50(3):1602425. doi: 10.1183/13993003.02425-2016. Print 2017 Sep.