A Multi-center, Non-randomized, Non Blinded, Non-controlled Study to Investigate the Impact of Multiple Doses of BAY63-2521 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Patients With Interstitial Lung Disease Associated Pulmonary Hypertension.
The purpose of this study is to assess multiple ascending doses of a new drug (BAY63-2521) given orally, to evaluate if it is safe and can help to improve the well-being, symptoms (e.g. disturbed breathing) and outcome of pulmonary hypertension associated with lung fibrosis. Patients living with pulmonary hypertension associated with interstitial lung disease have a risk of increased number of hospitalisations because of worsening of their condition. Until now there is no approved medication for this disease. The current treatment of pulmonary hypertension associated with interstitial lung disease consists: of oxygen and medical treatment with vasodilators, e.g. so-called Calcium-antagonists. Therefore, there is a need for new drugs in the treatment of pulmonary hypertension associated with interstitial lung disease.
• Diagnosis of an interstitial lung disease (usual interstitial pneumonia \[UIP\], nonspecific interstitial pneumonia \[NSIP\] or sarcoidosis) with high resolution CT and a total lung capacity (TLC) ≤ 90% or scleroderma associated pulmonary arterial hypertension (PAH) with total lung capacity (TLC) ≤ 80%.
• Interstitial lung disease (ILD) must have been stable for at least 3 months (decrease in forced vital capacity (FVC)\< 10% and diffusing capacity of lung for carbon monoxide (DLco) \< 15 % in 3 months), i.e. no significant changes in pulmonary function testing and stable medication in terms of ILD (e.g., corticosteroids, immunosuppressants)
• Mean pulmonary vascular resistance (PVR) \> 400 dyne sec cm-5 or mean pulmonary arterial pressure (PAP mean) \> 30 mmHg
• Pulmonary capillary wedge pressure (PCWP) \< 15 mmHg
• Hemodynamic parameters at baseline (PAP, PCWP, cardiac output \[CO\], systemic mean arterial pressure \[SAP\])
• High resolution computer tomography (HRCT) (should not be older than 12 months prior start of the study)
• Heart rate \> 55 beats per minute (BPM) and \< 105 BPM at rest
• Systolic blood pressure (SBP) \> 90 mmHg
• World Health Organisation (WHO) functional class II, III and IV
• 6 Minute Walking Test (6MWT) \> 100m and \< 450 m
• Stable controlled arterial hypertension according to current guidelines
• Women of childbearing potential will be included in the study if the pregnancy test is negative and combination of condoms with a safe and highly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain intra-uterine devices \[IUDs\]) is granted.