Riociguat in Scleroderma Associated Digital Ulcers

Exclusion Criteria

• •1. Active DU related to calcinosis (as assessed by clinical examination or radiographic evaluation at screening)
• •2. Medical and surgical history
• •* Major surgery (including joint surgery) within 8 weeks prior to screening
• •* Participants with a history of malignancy in the last 5 years other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ
• •3. Hepatic-related criteria
• •\- Hepatic insufficiency classified as Child-Pugh C at screening (see Appendix 11.1 for classification table) at screening visit
• •4. Renal-related criteria
• •* Estimated glomerular filtration rate (eGFR) \< 15 mL/min/1.73m2 (MDRD formula) or on dialysis at the screening visit
• •* Cardiovascular-related criteria
• •* Sitting systolic blood pressure \< 95 mmHg at the screening visit
• •* Sitting heart rate \< 50 beats per minute (BPM) at the screening visit
• •* Left ventricular ejection fraction \< 40% prior to screening on echocardiogram done as part of clinical care
• •5. Pulmonary-related criteria
• •* 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
• •* PAH requiring pharmacologic therapy.
• •* Significant pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted
• •6. Laboratory examinations
• •\- Participants with hemoglobin \< 9.0 g/dL, white blood cell (WBC) count \< 3000/mm3 (\< 3 × 109/L), platelet count \< 100,000/mm3 (\< 3 × 109/L) at the screening visit
• •7. Prior and concomitant therapy
• •* Concomitant use of nitrates or NO donors (such as amyl nitrate) in any form, including topical; phosphodiesterase (PDE) 5 (PDE5) inhibitors (such as sildenafil, tadalafil, vardenafil); and nonspecific PDE5 inhibitors (theophylline,dipyridamole). If the patient is on PDE5 inhibitors, a wash out of 3 days is required for sildenafil and 7 days for tadalafil or vardenafil prior to the baseline visit
• •* Concomitant Endothelin receptor antagonist
• •* Patients who are actively smoking at time of consent. (Quit date of two weeks prior to screening acceptable)
• •8. Pregnant or breastfeeding women
• •9. Other
• •* Any other condition or therapy that would make the participant unsuitable for this study and will not allow participation for the full planned study period
• •* Participation in another clinical study with an investigational drug or medical device within 30 days prior to randomization (phase I-III clinical studies)