Efficacy and Safety of Riociguat in Patients With Symptomatic Pulmonary Hypertension (PH) Associated With Idiopathic Interstitial Pneumonias (IIP)
Condition: Idiopathic Interstitial Pneumonias / Hypertension,Pulmonary
MeSH terms: Pneumonia; Hypertension, Pulmonary; Lung Diseases, Interstitial; Idiopathic Interstitial Pneumonias; Hamman-Rich Syndrome; Pulmonary Fibrosis; Hypertension
Intervention: Riociguat (Adempas, BAY63-2521); Placebo
Intervention description: Active drug 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration. The starting dose will be 0.5 mg TID, and the dose will be adjusted every two weeks for ten weeks in 0.5 mg increments up to a maximum dose of 2.5 mg TID based on patient's systolic blood pressure and well-being.; Inactive dosed at 0.5 mg, 1.0 mg, 1.5 mg, 2.0 mg and 2.5 mg TID/day as per individual dose titration for 26 weeks
Intervention MeSH terms: Riociguat
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 147.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      To evaluate the efficacy and safety of 26-weeks of treatment with riociguat vs. placebo in
      patients with symptomatic PH (pulmonary hypertension) associated with IIP (idiopathic
      interstitial pneumonias).
    

Eligibility criteria:

        -  Inclusion Criteria:

          -  Men or women aged from ≥18 to ≤80 years

          -  Diagnosed with one of the following (confirmed using a multidisciplinary approach, as
             per ATS(American Thoracic Society) / ERS(European Respiratory Society) / JRS (Japanese
             Respiratory Society) / ALAT(Latin American Thoracic Association) guidelines:

               -  Major IIPs (idiopathic interstitial pneumonias) diagnosis or suspected as one of
                  the following:

               -  Idiopathic pulmonary fibrosis

               -  Idiopathic nonspecific interstitial pneumonia

               -  Respiratory bronchiolitis-interstitial lung disease

               -  Desquamative interstitial pneumonia

               -  Cryptogenic organizing pneumonia

               -  Acute interstitial pneumonia

               -  Rare IIPs diagnosis by one of the following:

               -  Idiopathic lymphoid interstitial pneumonia

               -  Idiopathic pleuroparenchymal fibroelastosis

               -  Unclassifiable idiopathic interstitial pneumonias

          -  Forced Vital Capacity (FVC) ≥ 45 %

          -  6MWD (6 minutes walking distance) ≥ 150 m to ≤ 450 m {under stable O2(oxygen)
             supplementation via nasal cannula}

          -  Diagnosis of PH (pulmonary hypertension) confirmed by right heart catheter (RHC) with
             (mean artery pulmonary artery pressure )mPAP ≥ 25 mmHg and (pulmonary artery wedge
             pressure)PAWP ≤15 mmHg at rest

          -  Systolic blood pressure (SBP) ≥ 95 mmHg and no signs or symptoms of hypotension

          -  WHO functional class II-IV

          -  Women of childbearing potential can only be included in the study if a pregnancy test
             is negative. Women of childbearing potential must agree to use adequate contraception
             when sexually active. 'Adequate contraception' is defined as any combination of at
             least 2 effective methods of birth control, of which at least one is a physical
             barrier (e.g. condoms with hormonal contraception or implants or combined oral
             contraceptives, certain intrauterine devices). Adequate contraception is required from
             the signing of the informed consent form up until 4 weeks after the last study drug
             administration

          -  Exclusion Criteria:

          -  Known significant left heart disease:

               -  Pulmonary venous hypertension indicated by baseline pulmonary capillary wedge
                  pressure > 15 mmHg

               -  Symptomatic coronary artery disease

               -  Systolic left-ventricular dysfunction with an left ventricular ejection fraction
                  (LVEF) <45%

          -  Active state of hemoptysis or pulmonary hemorrhage, including those events managed by
             bronchial artery embolization

          -  Any history of bronchial artery embolization or massive hemoptysis within 3 months
             prior to screening. Massive hemoptysis being defined as acute bleeding >240 mL in a
             24-hour period or recurrent bleeding >100 mL/d over several days

          -  Difference > 15% between the eligibility and the baseline 6MWD test

          -  Forced expiratory volume in one second (FEV1) / Forced Vital Capacity (FVC) <0.65
             after bronchodilator administration

          -  Initiation in cytotoxic, immunosuppressive, cytokine modulating therapy initiated
             within 3 months prior to screening. Such agents might include. azathioprine,
             cyclophosphamide, corticosteroids, etanercept, tumor necrosis factor alpha (TNFα)
             inhibitors and others

          -  Any specific treatment for (pulmonary arterial hypertension) PAH/PH (pulmonary
             hypertension )within 3 months prior to screening

          -  Concomitant use of the following medication: nitrates or (nitric oxide) NO donors
             (such as amyl nitrite) in any form, phosphodiesterase 5 inhibitors (such as
             sildenafil, tadalafil, vardenafil) and non-specific phosphodiesterase (PDE) inhibitors
             (theophylline, dipyridamole),

          -  Pregnant women (i.e. positive pregnancy test or other signs of pregnancy), or breast
             feeding women, or women of childbearing potential not using adequate contraception (as
             defined in the aforementioned inclusion criterion) and not willing to agree to 4
             weekly pregnancy testing from Visit 1(first administration of study drug) onwards
             until 4 weeks after last study drug intake