A Phase 3 Study of Extended-release Tacrolimus in Subjects With Pulmonary Arterial Hypertension and Functional Limitations

Inclusion criteria

• WHO Group 1 PH: Pulmonary Arterial Hypertension;
• WHO functional class II - IV despite optimized treatment with one or more modalities. Treatments for PAH must be stable for at least 3 months at the time of screening;
• Right heart catheterization (RHC) at screening (or within 3 months prior to screening);
• Screening 6MWD >75 meters to ≤450 meters.

Exclusion criteria

• PAH due to pulmonary veno-occlusive disease or pulmonary capillary hemangiomatosis
• Chronic thromboembolic or portopulmonary hypertension
• Total Lung Capacity (TLC) <60% predicted;
• FEV1/FVC <70% predicted or FEV1 <60% predicted;
• Evidence of left-sided heart disease;
• Inability to safely attempt completion of the 6MWD;
• Life expectancy <6 months;
• eGFR <30 mL/min/1.73 m2 (CKD-EPI equation);
• Moderate to severe hepatic dysfunction (Child-Pugh score >10);
• Serum potassium >5.1 mEq/L;
• Use of experimental PAH treatments within the past 3 months;
• Active infection requiring antibiotic, antifungal, or antiviral therapies;
• Current systemic treatment with cyclosporine;
• Known allergy or hypersensitivity to tacrolimus;
• Significant psychiatric, addictive, or other disorder that compromises the subject's ability to provide informed consent, follow study protocol, or adhere to study treatment