Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH) - LARIAT

Inclusion Criteria

• Adult male and female patients ≥ 18 to ≤ 75 years of age upon study consent;
• BMI > 18.5 kg/m²
• Symptomatic pulmonary hypertension WHO class II and III;
• WHO Group I, III, or V PH according to the following criteria:
• If diagnosed with WHO Group I PAH, then on of the following subtypes:
• Idiopathic or heritable PAH;
• PAH associated with connective tissue disease;
• PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair;
• PAH associated with anorexigen or drug-induced toxicity;
• PAH associated with human immunodeficiency virus (HIV); or
• If WHO Group III PH then primary diagnosis must be one of the following subtypes:
• Connective tissue disease associated ILD (CTD-ILD);
• Idiopathic pulmonary fibrosis (IPF);
• Nonspecific interstitial pneumonia (NSIP); or
• If WHO Group V PH then patient must be diagnosed with sarcoidosis;
• Had a diagnostic right heart catheterization performed and documented within 36 months prior to Day 1 that confirmed a diagnosis of PH
• If WHO Group I, has been receiving no more than three (3) FDA-approved disease-specific PAH therapies except for intravenous (iv) prostacyclin/prostacyclin analogues. PAH therapy must be at a stable dose for at least 90 days prior to Day 1;
• Has adequate kidney function defined as an estimated glomerular filtration rate (eGFR) ≥ 45 mL/min/1.73 m2 using the Modification of Diet in Renal Disease (MDRD) 4-variable formula;

Exclusion Criteria

• Participation in other interventional clinical studies involving pharmaceutical products being tested or used in a way different from the approved form or when used for an unapproved indication within 30 days prior to Day 1;
• Initiation of an exercise program for cardio-pulmonary rehabilitation within 3 months (90 days) prior to Day 1 or planned initiation during Part 1 of the study;
• Stopped receiving any PH chronic therapy within 60 days prior to Day 1;
• Requirement for receipt of intravenous inotropes within 30 days prior to Day 1;
• Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mm Hg or sitting diastolic blood pressure > 100 mm Hg during Screening after a period of rest;
• Has systolic BP 4 L/min and have peripheral capillary oxygen saturation levels the upper limit of normal (ULN) at Screening;
• For patients with HIV-associated PAH, any of the following:
• Concomitant active opportunistic infections within 180 days prior to Screening;
• Detectable viral load within 90 days prior to Screening;
• Cluster designation (CD+) T-cell count < 200 mm3 within 90 days prior to Screening;
• Changes in antiretroviral regimen within 90 days prior to Screening;
• Using inhaled pentamidine