Connective Tissue Disease-Associated Pulmonary Arterial Hypertension
Conditions
Interventions
Bardoxolone methyl or placebo will be administered orally once a day for 24
weeks. Bardoxolone methyol will be administered at a dose of 2.5, 5, or 10 mg.
Sponsors
Reata Pharmaceuticals, Inc.
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Adult male and female patients >= 18 to 18.5 kg/m2 3. Symptomatic pulmonary hypertension WHO/NYHA FC class II and III; 4. WHO Group I PAH associated with connective tissue disease; 5. Had a diagnostic right heart catheterization performed and documented within 36 months prior to Day 1 that confirmed a diagnosis of PAH according to all the following criteria: a. Mean pulmonary artery pressure >= 25 mm Hg (at rest); b. Pulmonary capillary wedge pressure (PCWP) ; 240 dyn•sec/cm5 or > 3 mm Hg/liter (L)/minute; 6. Has BNP level = 150 meters on two consecutive tests performed on different days prior to randomization, with a percent difference = 65% (predicted); 12. Had a ventilation-perfusion (V/Q) lung scan, spiral/helical/electron beam computed tomography (CT), or pulmonary angiogram prior to Day 1 that shows no evidence of thromboembolic disease (i.e., should note normal or low probability for pulmonary embolism). If V/Q scan was abnormal (i.e., results other than normal or low probability), then a confirmatory CT or selective pulmonary angiography must exclude chronic thromboembolic pulmonary hypertension; 13. Has adequate kidney function defined as an estimated glomerular filtration rate (eGFR) >= 45 mL/min/1.73 m2 as measured by the central lab; 14. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures; 15. Evidence of a personally signed and dated informed consent document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study prior to initiation of any patient-mandated procedures.
Exclusion criteria
Exclusion criteria: 1. Participation in other investigational clinical studies involving interventional 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 90 days prior to Day 1 or planned initiation during the study;;3. Stopped receiving any PAH chronic therapy within 60 days prior to Day 1;;4. Received a dose of prednisone > 20 mg/day (or equivalent dose if other corticosteroid) within 30 days prior to Day 1;;5. Received intravenous (iv) or subcutaneous (sc) prostacyclin/prostacyclin analogues within 90 days prior to Day 1; ;6. Received intravenous inotropes within 30 days prior to Day 1;;7. Has uncontrolled systemic hypertension as evidenced by sitting systolic blood pressure (BP) > 160 mm Hg or sitting diastolic BP >; 100 mm Hg during Screening after a period of rest; ;8. Has systolic BP 65 years; b. BMI >= 30 kg/m2; c. History of systemic hypertension; d. History of type 2 diabetes; e. History of atrial fibrillation;;12. History of atrial septostomy within 180 days prior to Day 1;;13. Uncontrolled obstructive sleep apnea;;14. 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);;15. Serum aminotransferase (ALT or AST) levels > 1.5X the upper limit of normal (ULN) at Screening;;16. Hemoglobin (Hgb) concentration < 10.5 g/dL at Screening;;17. Diagnosis of Down syndrome;;18. History of malignancy within 5 years prior to Screening, with the exception of localized skin or cervical carcinomas;;19. Untreated or uncontrolled active bacterial, fungal, or viral infection; ;20. Known or suspected active drug or alcohol abuse, per investigator judgment;;21. Use of inhaled nitric oxide within 7 days prior to Screening and Day 1 visits, excluding acute vasodilator testing during diagnostic cardiac catheterization;;22. Major surgery within 30 days prior to Day 1 or planned to occur during the course of the study;;23. Unwilling to practice acceptable methods of birth control (both males who have partners of childbearing potential and females of childbearing potential) during Screening, while taking study drug, and for at least 30 days after the last dose of study drug is ingested;;24. Women who are pregnant or breastfeeding;;25. Any disability or impairment that would prohibit performance of the 6MWT;;26. Any abnormal laboratory level that, in the opinion of the investigator, would put the patient at risk by tria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary Efficacy Endpoint: Change from baseline in six-minute-walk distance (6MWD) relative to placebo at Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary Efficacy Endpoint: Time-to-first clinical improvement event consisting of a persistent change for any of the following: - Improvement by at least one WHO functional class - Increase from baseline in 6MWD by at least 10% - Decrease from baseline in creatine kinase (as a surrogate biomarker for muscle injury and inflammation) by at least 10% | — |
Countries
Netherlands
Outcome results
None listed