This study evaluates the effects of VI-0106 (an extended-release formulation of tacrolimus) in participants with pulmonary arterial hypertension (PAH) who continue to have functional limitations despite being on optimized background PAH therapy. Participants will be randomly assigned with equal chance to receive either VI-0106 or placebo in a double-blind fashion to assess whether VI-0106 improves outcomes in this population.

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