An open-label, uncontrolled and non-blinded study to assess different doses of a new drug (Bay 63-2521), given orally as multiple ascending doses, to evaluate if it is safe and can help to improve the well-being of patients with interstitial lung disease associated pulmonary hypertension by lowering the pulmonary artery blood pressure.

• Register: EUCTR
• Last refreshed on: 27 November 2023
• Main ID: EUCTR2007-003928-37-DE
• Date of registration: 19/03/2008
• Prospective Registration: Yes
• Primary sponsor: Bayer AG
• Public title: An open-label, uncontrolled and non-blinded study to assess different doses of a new drug (Bay 63-2521), given orally as multiple ascending doses, to evaluate if it is safe and can help to improve the well-being of patients with interstitial lung disease associated pulmonary hypertension by lowering the pulmonary artery blood pressure.
• Scientific title: A multicenter, non-randomized, non-blinded, non-controlled study to investigate the impact of multiple doses of BAY 63-2521 on safety, tolerability, pharmacokinetics and pharmacodynamics in patients with interstitial lung disease associated pulmonary hypertension
• Date of first enrolment: 14/07/2008
• Target sample size: 23
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2007-003928-37
• 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
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Germany

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
The following inclusion criteria must be met at the pre-study examination:
Men and women aged > 18 years.
Diagnosis of an interstitial lung disease (UIP, NSIP or sarcoidosis) with high resolution CT and a total lung capacity (TLC) ILD must have been stable for at least 3 months (decrease in FVC <10% and DLcO < 15% in 3months), i.e. no significant changes in pulmonary function testing and stable medication in terms of ILD (e.g. corticosteroids, immunosuppressants).
WHO functional class II, III and IV.
6MWT > 100 m and < 450 m
Stable controlled arterial hypertension according to current guidelines.
meanPVR > 400 dyne sec cm-5 or PAP mean > 30 mmHg
PCWP > 15 mmHg
Hemodynamic parameters at baseline (PAP, PCWP, CO, SAP).
HRCT (should not be older than 12 months prior start of the study).
Heart rate > 55 BPM and < 105 BPM at rest.
SBP > 90 mmHg
Women of childbearing potential will be included in the study if the pregnancy test is negative and combination of condoms with a safe and higly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain IUDs) is granted.
Completion of a physical examination.
Subjects who are able to understand and follow instructions and who are able to participate in the study for the entire period.
Subjects must have given their written informed consent to participate in the study after receiving adequate previous infomation and prior to any study specific procedures.
Right-heart catheterisation for measurement of hemodynamic paramters and HRCT for the definite diagnosis of ILD associated PH must have been performed independently of this study. Hemodynamic measurement results should not be older than 3 months ad HRCT must not be older than 12 months at study start.

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 12
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 11

Exclusion criteria:
The following factors determined at the pre-study examination will automatically exclude the patient from participating in the trial:

Co-medication:
Patients pretreated with an off label use of specific medication for PAH like endothelin receptor antagonists, prostaglandins or PDE 5 blockers are excluded from the trial.
Requirement for concomitant use of nitrates are contraindicated.

Pre-existing clinically relevant lung disease other than ILD including
-bronchial asthma and COPD with a FEV1/FVC<60% pred., active tuberculosis
-pulmonary hypertension of another WHO group (I, II, IV, V)
-severe congenital abnormalities of the lungs, thorax and diaphragm
-clinical or radiological evidence of a pulmovenoocclusive disease (PVOD).

Systemic hemodynamics
Acute or severe chronic left heart failure.
Severe coronary artery disease (CAD; EF < 50%); CAD patients must be asymptomatic and stable.
Congenital or acquired valvular or myocardial disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension

Pulmonary function

TLC predicted >30%
FEV1 (related to VC) < 60% predicted

Blood gases at room air

-PaCO2 > 45 mmHg
-PaCO2 < 50 mmHg

Peripheral organ function

Moderate or severe hepatic insufficiency (Child-Pugh Class Band C and/or total bilirubin> 2.5mg/dl (43 µmol/L); and/or hepatic transaminases > 3 ULN.
-Moderate or severe renal insufficiency (creatinine > 2 mg/dl) or creatinine clearance according to Cockroft-Gault formula < 35 mL/min.

Others
Previous therapeutic radiation of lungs or mediastinum.
Concomitant participation in anoter trial or study.
Therapy with another investigational product within 30 days prior start of the study.
Women with pregnancy, breast feeding or with childbearing potential lacking combination of condoms and a safe and highly effective contraception method (hormonal contraception wth implants or combined oral contraceptives, certain IUDs).
Patients whose underlying disease is not likely to permit them to survive the study.
Excluded Therapies (see section 4.5.7)


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

Health Condition(s) or Problem(s) studied

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

Patients with interstitial lung disease associated pulmonary hypertension
MedDRA version: 21.1 Level: PT Classification code 10037400 Term: Pulmonary hypertension System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders

Intervention(s)

Product Name: riociguat 0.5 mg
Product Code: BAY 63-2521
Pharmaceutical Form: Film-coated 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-

Product Name: riociguat 1.0 mg
Product Code: BAY 63-2521
Pharmaceutical Form: Film-coated 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-

Product Name: riociguat 1.5 mg
Product Code: BAY 63-2521
Pharmaceutical Form: Film-coated 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-

Product Name: riociguat 2.0 mg
Product Code: BAY 63-2521
Pharmaceutical Form: Film-coated 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-

Product Name: riociguat 2.5 mg
Product Code: BAY 63-2521
Pharmaceutical Form: Film-coated 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: main phase 12 weeks followed by a long term extension until approval and commercially available

Primary end point(s): safety and efficacy (AEs)

Secondary Objective: Secondary objectives of the study are to assess the efficacy parameters and pharmacokinetics of BAY 63-2521 during the course of the study in patients with pulmonary hypertension due to interstitial lung disease.

Main Objective: Main objective of the trial is to investigate the safety and tolerability of a 12-week treatment with BAY 63-2521 of patients with pulmonary hypertension due to intestinal lung disease (ILD idiopathic pulmonary fibrosis, non-specific interstitial pneumonia, sarcoidosis, scleroderma.

Secondary Outcome(s)

Secondary end point(s): pharmacokinetics and efficacy:
Pharmacokinetics
6MWT
modified Borg dyspnea score
Quality of life assessments (SF-36; Euroqol)
Hemodynamic parameters
Laboratory samples
Electrocardiogram (ECG)
Blood Pressure and heart rate

Timepoint(s) of evaluation of this end point: For all: Main phase 12 weeks followed by a long term extension (LTE).

Pharmacokinetics, modified Borg dyspnea score, Quality of life assessments (SF-36; Euroqol), Hemodynamic parameters, Laboratory samples, Electrocardiogram (ECG)
stopped during LTE with amendment 4.

6MWT and heart rate ongoing until approval and commercially available.

Secondary ID(s)

BAY63-2521/12916

Source(s) of Monetary Support

Bayer AG

Ethics review

Status: Approved
Approval date: 29/05/2008
Contact: