Bardoxolone Methyl Evaluation in Patients With Pulmonary Hypertension (PH)

Phase 1

Conditions: Pulmonary Hypertension
MedDRA version: 19.1Level: HLTClassification code 10037401Term: Pulmonary hypertensionsSystem Organ Class: 100000004855
Therapeutic area: Diseases [C] - Respiratory Tract Diseases [C08]

Registration Number: EUCTR2016-004793-17-ES

Lead Sponsor: Reata Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 198

Inclusion Criteria

1.Adult male and female patients = 18 to = 75 years of age upon study consent;
2. MI > 18.5 kg/m2;
3.Symptomatic pulmonary hypertension WHO Functional Class II and III;
4.WHO Group I, III, or V PH according to the following criteria:
a.If diagnosed with WHO Group I PAH, then one of the following subtypes:
i.Idiopathic or heritable PAH;
ii.PAH associated with connective tissue disease;
iii.PAH associated with simple, congenital systemic-to-pulmonary shunts at
least 1 year following shunt repair;
iv.PAH associated with anorexigen or drug-induced toxicity;
v.PAH associated with human immunodeficiency virus (HIV); or
b.If WHO Group III PH, then primary diagnosis must be one of the following subtypes:
i.Connective tissue disease associated ILD (CTD-ILD);
ii.Idiopathic pulmonary fibrosis according to the American Thoracic Society and European Respiratory Society (ATS/ERS) guidelines (Raghu 2011);
iii.Nonspecific interstitial pneumonia (NSIP) or the following idiopathic interstitial pneumonia subtypes, according to the American Thoracic Society and European Respiratory Society (ATS/ERS) guidelines (Travis 2013):
1.Respiratory bronchiolitis-associated interstitial lung disease;
2.Desquamative interstitial pneumonia;
3.Cryptogenic organizing pneumonia;
4.Acute interstitial pneumonitis;
5.Idiopathic lymphoid interstitial pneumonia;
6.Idiopathic pleuroparenchymal fibroelastosis;
7.Unclassifiable idiopathic interstitial pneumonia, including patients who have not had a lung biopsy; or
c.If WHO Group V PH, then patient must be diagnosed with sarcoidosis;
5.Had a diagnostic right heart catheterization performed and documented prior to Day 1 that confirmed a diagnosis of PH according to all the following criteria:
a.If diagnosed with WHO Group I PAH, then:
i.Mean pulmonary artery pressure = 25 mm Hg (at rest);
ii.Pulmonary capillary wedge pressure (PCWP) = 15 mm Hg;
iii.Pulmonary vascular resistance > 240 dyn.sec/cm5 or > 3 mm Hg/Liter (L)/minute;
b.If not diagnosed with WHO Group I PAH, then:
i.Mean pulmonary artery pressure = 21 mm Hg (at rest);
ii.Pulmonary capillary wedge pressure (PCWP) = 15 mm Hg;
iii.Pulmonary vascular resistance > 160 dyn.sec/cm5
6.Has BNP level = 400 pg/mL;
7.Has an average 6-minute walk distance = 150 meters on two consecutive tests
performed on different days prior to randomization, with both tests measuring within 15% of one another;
8.Has been receiving no more than two (2) approved disease-specific PAH therapies. Cohort
3b WHO Group I PAH patients enrolled outside the United States must be receiving zero (0)or one (1) PAH therapies. PAH therapy must be at a stable dose for at least 90 days prior to Day 1;
9.If WHO Group III or WHO Group V, disease-specific therapy must be at a stable dose for 30 days;
10.Has maintained a stable dose for 30 days prior to Day 1 if receiving any of the following
therapies that may affect PH: vasodilators (including calcium channel blockers), digoxin,
L-arginine supplementation, or oxygen supplementation;
11.If receiving prednisone, has maintained a stable dose of = 20 mg/day (or equivalent dose if other corticosteroid) for at least 30 days prior to Day 1. If receiving treatment for
CTD with any other drugs, doses should remain stable for the duration of the study;
12.Had PFTs within 90 days prior to Day 1 that meet the following criteria:
a.For WHO GroupI PAH patients with connective tissue disease, total lung capacity (TLC) = 65% (predicted);
b.For

Exclusion Criteria

1. Participation in other investigational 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. 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;
6. Has systolic BP < 90 mm Hg during Screening after a period of rest;
7. WHO Group III patients with pulmonary hypertension primarily associated with chronic
obstructive pulmonary disease, sleep-disordered breathing, and/or alveolar hypoventilation
disorders;
8. WHO Group III or V patients who at rest require supplemental oxygen at a rate > 4 L/min or have peripheral capillary oxygen saturation (SpO2) levels < 92%;
9. 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:
a. Congenital or acquired valvular disease if clinically significant apart from tricuspid
valvular insufficiency due to pulmonary hypertension;
b. Pericardial constriction;
c. Restrictive or congestive cardiomyopathy;
d. Left ventricular ejection fraction < 40% per echocardiogram (ECHO) within 60 days of Day 1;
e. Any current or prior history of symptomatic coronary disease (prior myocardial
infarction, percutaneous coronary intervention, coronary artery bypass graft surgery,
or anginal chest pain);
10. Clinical instability within 8 weeks prior to Day 1, such as hospitalization due to respiratory or cardiac symptoms, acutely decompensated heart failure, syncope, or other events that in the investigator’s opinion would suggest the patient is an inappropriate candidate for the study;
11. Has more than two of the following clinical risk factors for left ventricular diastolic
dysfunction:
a. Age > 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. Obstructive sleep apnea that is untreated;
14. For patients with HIV-associated PAH, any of the following:
a. Concomitant active opportunistic infections within 180 days prior to Screening;
b. Detectable viral load within 90 days prior to Screening;
c. Cluster designation 4 (CD4+) T-cell count < 200 mm3 within 90 days prior to Screening;
d. Changes in antiretroviral regimen within 90 days prior to Screening;
e. Using inhaled pentamidine;
15. 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);
16. Serum aminotransferase (ALT or AST) levels > 1.5X the upper limit of normal (ULN) at
Screening;
17. Hemoglobin (Hgb) concentration < 10.5 g/dL at Screening;
18. Diagnosis of Down syndrome;
19. History of malignancy within 5 years prior to screening, with the exception of localized skin or cervical carcinomas;
20. Active bacterial, fu