Open-label, international, multicenter, non-placebo controlled (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)

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2013-001759-10-DE
• Date of registration: 15/10/2013
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: Open-label, international, multicenter, non-placebo controlled (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)
• Scientific title: 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) - RESPITE
• Date of first enrolment: 03/01/2014
• Target sample size: 70
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-001759-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Canada, Czech Republic, Germany, Switzerland, United Kingdom, United States

Contacts

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

• Name: Bayer Clinical Trials Contact
• Affiliation: Bayer AG

Key inclusion & exclusion criteria

Inclusion criteria:
• Male or female patients (18 -75 years of age) with idiopathic, heritable, drug/toxin induced PAH or associated PAH due to congenital heart disease (i.e. atrial septal defects if corrected for more than 12 months) 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 of 165-440 m
• Cardiac index <3.0 L/min/m2.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 55
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

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 in the judgment of the investigator (e.g. based on a clean CT lung scan)
• 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 woman (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


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Hypertension, Pulmonary

Intervention(s)

Trade Name: Adempas
Product Name: BAY 63-2521 Tablet
Product Code: BAY 63-2521
Pharmaceutical Form: Tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY 63-2521
Other descriptive name: RIOCIGUAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-

Trade Name: Adempas
Product Name: BAY 63-2521 Tablet
Product Code: BAY 63-2521
Pharmaceutical Form: Tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY 63-2521
Other descriptive name: RIOCIGUAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.0-

Trade Name: Adempas
Product Name: BAY 63-2521 Tablet
Product Code: BAY 63-2521
Pharmaceutical Form: Tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY 63-2521
Other descriptive name: RIOCIGUAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1.5-

Trade Name: Adempas
Product Name: BAY 63-2521 Tablet
Product Code: BAY 63-2521
Pharmaceutical Form: Tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY 63-2521
Other descriptive name: RIOCIGUAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.0-

Trade Name: Adempas
Product Name: BAY 63-2521 Tablet
Product Code: BAY 63-2521
Pharmaceutical Form: Tablet
INN or Proposed INN: Riociguat
CAS Number: 625115-55-1
Current Sponsor code: BAY 63-2521
Other descriptive name: RIOCIGUAT
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2.5-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Not applicable

Main Objective: To investigate whether it is safe, feasible and beneficial to replace PDE-5i therapy with Riociguat in PAH patients demonstrating insufficient response to PDE-5 inhibition.

Secondary Objective: Not applicable

Primary end point(s): There is no primary endpoint in this study. All efficacy variables are exploratory.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: After 12 and 24 weeks (except for change in cardiac index: after 24 weeks only)

Secondary end point(s): • Change from baseline in 6 minute walking distance.
• Change in cardiac index.
• Change in N-terminal pro-brain natriuretic peptide.
• Change in World Health Organization functional class.
• Proportion of patients with clinical worsening.
• Change in quality of life EuroQol questionnaire.
• Change in quality of life Living with pulmonary hypertension questionnaire.
• Proprtion of patients without clinical worsening who achieve at least World Health Organization functional class II and an improvement in 6 minute walking distance of greater than or equal to 30 metres.

Secondary ID(s)

Bay63-2521/16719

NCT02007629

Source(s) of Monetary Support

Bayer AG