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

纳入标准：

1. Adult male and female patients ≥ 18 to ≤ 75 years of age upon study consent;
2. BMI > 18.5 kg/m²
3. Symptomatic pulmonary hypertension WHO class II and III;

4. WHO Group I, III, or V PH according to the following criteria:

   1. 如果被诊断出患有我的I组PAH，则按照以下子类型进行：

      • Idiopathic or heritable PAH;
      • pahassociated with connective tissue disease;
      • pahassociated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair;
      • pahassociated with anorexigen or drug-induced toxicity;
      • 与人类免疫缺陷病毒（HIV）相关的PAH；或者

   2. 如果谁是III组PH，则主要诊断必须是以下亚型之一：

      • Connective tissue disease associated ILD (CTD-ILD);
      • 特发性肺纤维化(IPF);
      • Nonspecific interstitial pneumonia (NSIP); or
   3. If WHO Group V PH then patient must be diagnosed with sarcoidosis;
5. 如果在第1天前36个月内执行并记录了右心导管插入术，则证实了pH的诊断
6. 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;
7. 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:

1. 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;
2. 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;
3. Stopped receiving any PH chronic therapy within 60 days prior to Day 1;
4. Requirement for receipt of intravenous inotropes within 30 days prior to Day 1;
5. 坐着的收缩压（BP）> 160 mm Hg或静坐后舒适时舒适的舒张压> 100 mm Hg证明，具有不受控制的全身性高血压。
6. 休息一段时间后筛选期间的收缩压<90毫米汞柱；
7. 谁在休息时需要以> 4 l/min的速度补充氧气，并且外周毛细血管氧饱和度<92％；

8. Has a history of clinically significant left-sided heart disease and/or clinically significant cardiac disease,including but not limited to any of the following:

   1. Congenital or acquired valvular disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension;
   2. Pericardial constriction;
   3. Restrictive or congestive cardiomyopathy;
   4. Left ventricular ejection fraction < 40% per echocardiogram (ECHO) within 60 days of Day 1;
   5. Any current or prior history of symptomatic coronary disease (prior myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft surgery, or anginal chest pain);
9. Acutely decompensated heart failure within 30 days prior to Day 1, as per Investigator assessment;
10. History of atrial septostomy within 180 days prior to Day 1;
11. History of obstructive sleep apnea that is untreated;
12. Has a history of portal hypertension or chronic liver disease, including hepatitis B and/or hepatitis C (with evidence of recent infection and/or active virus replication) defined as mild to severe hepatic impairment (Child-Pugh Class A-C);
13. 血清氨基转移酶（ALT或AST）水平>筛选时正常（ULN）的上限；

14. For patients with HIV-associated PAH, any of the following:

    1. Concomitant active opportunistic infections within 180 days prior to Screening;
    2. 筛查前90天内可检测的病毒负荷；
    3. Cluster designation (CD+) T-cell count < 200 mm3 within 90 days prior to Screening;
    4. Changes in antiretroviral regimen within 90 days prior to Screening;
    5. Using inhaled pentamidine