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.
- Conditions
- Patients with interstitial lung disease associated pulmonary hypertensionMedDRA version: 21.1Level: PTClassification code 10037400Term: Pulmonary hypertensionSystem Organ Class: 10038738 - Respiratory, thoracic and mediastinal disordersTherapeutic area: Diseases [C] - Cardiovascular Diseases [C14]
- Registration Number
- EUCTR2007-003928-37-DE
- Lead Sponsor
- Bayer AG
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 23
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
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)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 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 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.;Primary end point(s): safety and efficacy (AEs);Timepoint(s) of evaluation of this end point: main phase 12 weeks followed by a long term extension until approval and commercially available
- Secondary Outcome Measures
Name Time Method Secondary end point(s): pharmacokinetics and efficacy:<br>Pharmacokinetics<br>6MWT<br>modified Borg dyspnea score<br>Quality of life assessments (SF-36; Euroqol)<br>Hemodynamic parameters<br>Laboratory samples<br>Electrocardiogram (ECG)<br>Blood Pressure and heart rate<br>;Timepoint(s) of evaluation of this end point: For all: Main phase 12 weeks followed by a long term extension (LTE). <br><br>Pharmacokinetics, modified Borg dyspnea score, Quality of life assessments (SF-36; Euroqol), Hemodynamic parameters, Laboratory samples, Electrocardiogram (ECG)<br>stopped during LTE with amendment 4.<br><br>6MWT and heart rate ongoing until approval and commercially available.