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Impact of Multiple Doses of BAY63-2521 on Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Patients With Interstitial Lung Disease (ILD) Associated Pulmonary Hypertension (PH)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00694850
First received: June 9, 2008
Last updated: August 28, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Hypertension, Pulmonary
Drug: Riociguat (Adempas, BAY63-2521)
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • Safety and tolerability [ Time Frame: 12 weeks treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Pharmacokinetics [ Time Frame: at every study visit except at run-in and Follow-up ] [ Designated as safety issue: No ]
    The assessment will be stopped after protocol amendment 4, which was effective since Jan 06, 2014

  • 6-Minute Walk Test [ Time Frame: at every study visit except at Follow-up ] [ Designated as safety issue: No ]
  • Modified borg scale [ Time Frame: at every study visit except at Follow-up ] [ Designated as safety issue: No ]
    The assessment will be stopped after protocol amendment 4, which was effective since Jan 06, 2014

  • Quality of life assessments [ Time Frame: at baseline, after 6 weeks, after 12 weeks, Follow-up and at each visit during long term extension phase ] [ Designated as safety issue: No ]
    The assessment will be stopped after protocol amendment 4, which was effective since Jan 06, 2014

  • Hemodynamic parameters [ Time Frame: optional after 12weeks ] [ Designated as safety issue: No ]
  • Laboratory Parameters [ Time Frame: at each study visit during run-in and treatment phase and long term extension ] [ Designated as safety issue: Yes ]
    The assessment will be stopped after protocol amendment 4, which was effective since Jan 06, 2014

  • Electrocardiogram (ECG) [ Time Frame: at each study visit during run-in and treatment phase and long term extension ] [ Designated as safety issue: Yes ]
    The assessment will be stopped after protocol amendment 4, which was effective since Jan 06, 2014

  • Blood pressure and heart rate [ Time Frame: at each study visit during run-in and treatment phase and long term extension ] [ Designated as safety issue: Yes ]

Enrollment: 22
Study Start Date: August 2008
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Riociguat (Adempas, BAY63-2521)
BAY63-2521 will be up-titrated from 1,0 mg TID to 2,5 mg TID

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • Co-medication:

    • Patients pretreated with specific medication for pulmonary arterial hypertension (PAH) like endothelin receptor antagonists, prostaglandins or phosphodiesterase type 5 (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 Chronic Obstructive Pulmonary Disease (COPD) with a forced expiratory volume in one second (FEV1)/FVC <60% pred., active tuberculosis
    • Pulmonary hypertension of another WHO group (I, II, IV and 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 (ejection fraction (EF) < 50%)
    • 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 FVC) < 60% predicted
  • Blood gases at room air

    • Arterial partial carbon dioxide pressure (Pa CO2) > 45 mmHg
    • Arterial partial oxygen pressure (Pa O2) < 50 mmHg at O2 supply >/= 4 L/min
  • Peripheral organ function

    • Moderate or severe hepatic insufficiency (Child-Pugh Class Band C and/or total bilirubin > 2.5 mg/dl (0.043 mmol/L); and/or hepatic transaminases >3 upper limit normal [ULN])
    • Moderate or severe renal insufficiency (creatinine > 2 mg/dl) or creatinine clearance according to Cockroft-Gault formula < 35 mL/ min
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00694850

Locations
Germany
München, Bayern, Germany, 81377
Gießen, Hessen, Germany, 35392
Hannover, Niedersachsen, Germany, 30625
Homburg, Saarland, Germany, 66421
Dresden, Sachsen, Germany, 01307
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00694850     History of Changes
Other Study ID Numbers: 12916, 2007-003928-37
Study First Received: June 9, 2008
Last Updated: August 28, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
Interstitial lung disease associated pulmonary hypertension

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Lung Diseases
Lung Diseases, Interstitial
Cardiovascular Diseases
Respiratory Tract Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 25, 2014