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



Status:Completed
Conditions:Bronchitis, Lung Cancer, High Blood Pressure (Hypertension), High Blood Pressure (Hypertension), Pneumonia, Women's Studies, Endocrine, Pulmonary, Pulmonary, Pulmonary
Therapuetic Areas:Cardiology / Vascular Diseases, Endocrinology, Oncology, Pulmonary / Respiratory Diseases, Reproductive
Healthy:No
Age Range:18 - 75
Updated:1/5/2019
Start Date:May 2014
End Date:May 16, 2018

Use our guide to learn which trials are right for you!

A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients With Pulmonary Hypertension

This study assesses the safety and efficacy of bardoxolone methyl relative to placebo in
patients with pulmonary hypertension to determine the recommended dose range, evaluate the
change from baseline in 6-minute walk distance (6MWD) and determine the effect of Bardoxolone
methyl in pulmonary hypertension associated with connective tissue disease, interstitial lung
disease, and idiopathic etiologies, including subsets of patients with WHO Group III or WHO
Group V PH following 16 weeks of study participation.

The molecular and pharmacological effects of bardoxolone methyl are broad through its
induction of Nrf2 and suppression of NF-κB. Bardoxolone methyl may therefore address multiple
facets of the pathophysiology of PH because it suppresses activation of proinflammatory
mediators, enhances endothelial NO bioavailability, improves metabolic dysfunction,
suppresses vascular proliferation, and prevents maladaptive remodeling. Furthermore, while
existing therapies primarily target only smooth muscle cells, bardoxolone methyl targets
multiple cell types relevant to PH, including endothelial cells, smooth muscle cells, and
macrophages.

This is a two-part study.

Part 1: Part 1 of the study will include a dose-ranging phase and a dose-titration phase.

Part 2 (extension period): All patients from Part 1 who complete the 16-week treatment period
as planned will be eligible to continue directly into the extension period to evaluate the
intermediate and long-term safety and efficacy of bardoxolone methyl.

Inclusion Criteria:

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. 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

2. 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

3. If WHO Group V PH then patient must be diagnosed with sarcoidosis;

5. Had a diagnostic right heart catheterization performed and documented within 36 months
prior to Day 1 that confirmed a diagnosis of PH

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. 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 or V patients who at rest require supplemental oxygen at a rate of >4
L/min and have peripheral capillary oxygen saturation levels <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. Serum aminotransferase (ALT or AST) levels > the upper limit of normal (ULN) at
Screening;

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

1. Concomitant active opportunistic infections within 180 days prior to Screening;

2. Detectable viral load within 90 days prior to Screening;

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
We found this trial at
31
sites
Littleton, Colorado 80120
Principal Investigator: Ira Dauber
Phone: 303-703-2124
?
mi
from
Littleton, CO
Click here to add this to my saved trials
800 Washington St
Boston, Massachusetts 02111
(617) 636-5000
Principal Investigator: Nicholas Hill, MD
Phone: 617-636-1334
Tufts Medical Center Tufts Medical Center is an internationally-respected academic medical center – a teaching...
?
mi
from
Boston, MA
Click here to add this to my saved trials
75 Francis street
Boston, Massachusetts 02115
(617) 732-5500
Principal Investigator: Aaron Waxman, MD
Phone: 305-613-9411
Brigham and Women's Hosp Boston’s Brigham and Women’s Hospital (BWH) is an international leader in...
?
mi
from
Boston, MA
Click here to add this to my saved trials
72 East Concord Street
Boston, Massachusetts 02118
(617) 638-5300
Principal Investigator: Elizabeth Klings, MD
Phone: 617-638-4475
Boston University School of Medicine A leader in medical education and research, Boston University School...
?
mi
from
Boston, MA
Click here to add this to my saved trials
5801 South Ellis Avenue
Chicago, Illinois 60637
 773.702.1234
Principal Investigator: Remzi Bag, MD
Phone: 773-702-5589
University of Chicago One of the world's premier academic and research institutions, the University of...
?
mi
from
Chicago, IL
Click here to add this to my saved trials
201 Presidents Circle
Salt Lake City, Utah 84108
801) 581-7200
Principal Investigator: John Ryan, MD
Phone: 801-585-2944
University of Utah Research is a major component in the life of the U benefiting...
?
mi
from
Salt Lake City, UT
Click here to add this to my saved trials
1000 W Carson St
Torrance, California 90502
Principal Investigator: Ronald J. Oudiz, MD
Phone: 310-222-3560
?
mi
from
Torrance, CA
Click here to add this to my saved trials
2950 Cleveland Clinic Blvd.
Weston, Florida 33331
866.293.7866
Principal Investigator: Franck Rahaghi, MD
Phone: 954-627-2820
Cleveland Clinic Florida Cleveland Clinic Florida, located in Weston, West Palm Beach, Palm Beach Gardens...
?
mi
from
Weston, FL
Click here to add this to my saved trials
13001 East 17th Place
Aurora, Colorado 80045
Principal Investigator: David Badesch, MD
Phone: 720-848-6552
?
mi
from
Aurora, CO
Click here to add this to my saved trials
Beverly Hills, California 90211
Principal Investigator: Victor Tapson, MD
Phone: 310-828-2878
?
mi
from
Beverly Hills, CA
Click here to add this to my saved trials
Cincinnati, Ohio 45219
Principal Investigator: Peter Engel, MD
Phone: 513-585-1707
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
3230 Eden Ave
Cincinnati, Ohio 45267
Principal Investigator: Jean Elwing, MD
Phone: 513-558-3257
?
mi
from
Cincinnati, OH
Click here to add this to my saved trials
410 W 10th Ave
Columbus, Ohio 43210
(614) 293-8652
Principal Investigator: Nitin Bhatt, MD
Phone: 614-366-2258
The Ohio State University, Wexner Medical Center Located in Columbus, The Ohio State University Wexner...
?
mi
from
Columbus, OH
Click here to add this to my saved trials
1801 Inwood Rd
Dallas, Texas 75390
(214) 645-3300
Phone: 214-645-6493
University of Texas Southwestern Medical Center UT Southwestern is an academic medical center, world-renowned for...
?
mi
from
Dallas, TX
Click here to add this to my saved trials
74 Fetscherstraße
Dresden, 01304
Principal Investigator: Michael Halank, MD
Phone: +49 0351-7965624
?
mi
from
Dresden,
Click here to add this to my saved trials
El Paso, Texas 79912
Principal Investigator: Hernando Garcia, MD
Phone: 915-225-4917
?
mi
from
El Paso, TX
Click here to add this to my saved trials
Houston, Texas 77030
Principal Investigator: Maureen Mayes, MD
Phone: 713-500-7118
?
mi
from
Houston, TX
Click here to add this to my saved trials
Houston, Texas 77030
Principal Investigator: Adanni Frost, MD
Phone: 713-363-7537
?
mi
from
Houston, TX
Click here to add this to my saved trials
7000 Fannin Street
Houston, Texas 77030
Principal Investigator: Bela Patel, MD
Phone: 713-500-6851
?
mi
from
Houston, TX
Click here to add this to my saved trials
Los Angeles, California 90073
Principal Investigator: Shelley Shapiro, MD
Phone: 310-268-4314
?
mi
from
Los Angeles, CA
Click here to add this to my saved trials
259 1st St
Mineola, New York 11501
(516) 663-0333
Principal Investigator: Shilpa DeSouza, MD
Phone: 516-663-9582
Winthrop University Hospital Founded in 1896 by a group of local physicians and concerned citizens,...
?
mi
from
Mineola, NY
Click here to add this to my saved trials
New York, New York 10065
Principal Investigator: Evelyn Horn, MD
Phone: 212-746-2698
?
mi
from
New York, NY
Click here to add this to my saved trials
New York, New York 10003
Principal Investigator: Roxana Sulica, MD
Phone: 201-230-5689
?
mi
from
New York, NY
Click here to add this to my saved trials
Oklahoma City, Oklahoma 73120
Principal Investigator: John Kingrey, MD
Phone: 405-608-1281
?
mi
from
Oklahoma City, OK
Click here to add this to my saved trials
Phoenix, Arizona 85004
Principal Investigator: Rajeev Saggar, MD
Phone: 602-839-6211
?
mi
from
Phoenix, AZ
Click here to add this to my saved trials
Phoenix, Arizona 85013
Principal Investigator: Jeremy Feldman, MD
Phone: 602-271-0832
?
mi
from
Phoenix, AZ
Click here to add this to my saved trials
200 Lothrop St
Pittsburgh, Pennsylvania 15213
Principal Investigator: Robyn Domsic, MD
Phone: 412-648-7040
University of Pittsburgh Medical Center UPMC is one of the leading nonprofit health systems in...
?
mi
from
Pittsburgh, PA
Click here to add this to my saved trials
Portland, Maine 04102
Principal Investigator: Joel Wirth, MD
Phone: 207-662-6550
?
mi
from
Portland, ME
Click here to add this to my saved trials
Rochester, New York 14642
Principal Investigator: Jim White, MD
Phone: 585-486-0869
?
mi
from
Rochester, NY
Click here to add this to my saved trials
Sacramento, California 95817
Principal Investigator: Roblee Allen, MD
Phone: 916-734-1554
?
mi
from
Sacramento, CA
Click here to add this to my saved trials
?
mi
from
Washington,
Click here to add this to my saved trials