Bardoxolone Methyl Evaluation in Patients With Pulmonary Arterial Hypertension (PAH) (LARIAT)

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Reata Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02036970
First received: January 13, 2014
Last updated: June 30, 2014
Last verified: June 2014
  Purpose

This study assesses the safety and efficacy of bardoxolone methyl relative to placebo in patients with pulmonary arterial hypertension to determine the recommended dose range and evaluate the change from baseline in 6-minute walk distance (6MWD) following 16 weeks of study participation.


Condition Intervention Phase
Pulmonary Arterial Hypertension
Drug: Bardoxolone methyl
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Dose-Ranging Study of the Efficacy and Safety of Bardoxolone Methyl in Patients With Pulmonary Arterial Hypertension

Resource links provided by NLM:


Further study details as provided by Reata Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Change from baseline in 6-Minute Walk Distance (6MWD) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 112
Study Start Date: May 2014
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Cohort 1: Dose 1
Bardoxolone methyl [Dose 1] mg capsules or placebo by mouth once daily x 16 weeks
Drug: Bardoxolone methyl
Other Name: RTA 402 capsules
Drug: Placebo
Placebo Comparator: Cohort 2: Dose 2
Bardoxolone methyl [Dose 2] mg capsules or placebo by mouth once daily x 16 weeks
Drug: Bardoxolone methyl
Other Name: RTA 402 capsules
Drug: Placebo
Placebo Comparator: Cohort 3: Dose 3
Bardoxolone methyl [Dose 3] mg capsules or placebo by mouth once daily x 16 weeks
Drug: Bardoxolone methyl
Other Name: RTA 402 capsules
Drug: Placebo
Placebo Comparator: Cohort 4: Dose 4
Bardoxolone methyl [Dose 4] mg capsules or placebo by mouth once daily x 16 weeks
Drug: Bardoxolone methyl
Other Name: RTA 402 capsules
Drug: Placebo
Placebo Comparator: Cohort 5: Dose 5
Bardoxolone methyl [Dose 5] mg capsules or placebo by mouth once daily x 16 weeks
Drug: Bardoxolone methyl
Other Name: RTA 402 capsules
Drug: Placebo

Detailed Description:

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 PAH 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 PAH, including endothelial cells, smooth muscle cells, and macrophages.

This is a two-part study.

Part 1: Part 1 of the study will include both dose-escalation and expansion cohorts.

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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Adult male and female patients ≥ 18 to ≤ 75 years of age upon study consent;
  2. Symptomatic pulmonary arterial hypertension WHO/NYHA FC class II and III;
  3. One of the following subtypes of WHO Group 1 PAH:

    1. Idiopathic or heritable PAH;
    2. PAH associated with connective tissue disease;
    3. PAH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair;
    4. PAH associated with anorexigens;
    5. PAH associated with human immunodeficiency virus (HIV);
  4. Had a diagnostic right heart catheterization performed and documented within 12 months prior to Screening that confirmed a diagnosis of PAH
  5. Has been receiving an oral, disease-specific PAH therapy consisting of an endothelin receptor antagonist (ERA) and/or a phosphodiesterase type-5 inhibitor (PDE5i). PAH therapy must be at a stable dose for at least 90 days prior to Day 1;
  6. Has adequate kidney function defined as an estimated glomerular filtration rate (eGFR) ≥ 60 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 within 30 days prior to Day 1;
  2. Participation in an intensive exercise training program for pulmonary rehabilitation within 90 days prior to Screening;
  3. Receiving chronic treatment with a prostacyclin/prostacyclin analogue or riociguat within 60 days prior to Day 1. Use of prostacyclin for acute vasodilator testing during right heart catheterization is allowed;
  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. Has a history of left-sided heart disease and/or clinically significant cardiac disease,including but not limited to any of the following:

    1. Aortic or mitral valve disease (stenosis or regurgitation) defined as greater than mild aortic insufficiency;
    2. Pericardial constriction;
    3. Restrictive or congestive cardiomyopathy;
    4. Left ventricular ejection fraction < 40% at the Screen A echocardiogram (ECHO);
    5. Evidence of left ventricular diastolic dysfunction;
    6. Left ventricular shortening fraction < 22% at the Screen A ECHO;
    7. Symptomatic coronary disease;
  8. Acutely decompensated heart failure within 30 days prior to Day 1, as per Investigator assessment;
  9. History of atrial septostomy within 180 days prior to Day 1;
  10. History of obstructive sleep apnea that is untreated;
  11. 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;
  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;
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02036970

Locations
United States, Arizona
Arizona Pulmonary Specialists Recruiting
Phoenix, Arizona, United States, 85012
Contact: Research Coordinator    602-271-0832      
Principal Investigator: Jeremy Feldman, MD         
United States, California
Harbor - UCLA Medical Center Recruiting
Torrance, California, United States, 90502
Contact: Research Coordinator    310-222-3560      
Principal Investigator: Ronald J. Oudiz, MD         
United States, Colorado
University of Colorado Cardiac and Vascular Center Recruiting
Aurora, Colorado, United States, 80045
Contact: Research Coordinator    720-848-6540      
Principal Investigator: David Badesch, MD         
South Denver Cardiology Recruiting
Littleton, Colorado, United States, 80120
Contact: Research Coordinator    303-715-2210      
Principal Investigator: Ira Dauber         
United States, Illinois
University of Chicago Medicine Recruiting
Chicago, Illinois, United States, 60637
Contact: Research Coordinator    773-702-5589      
Principal Investigator: Mardi Gomberg-Maitland, MD         
United States, Kentucky
Kentuckian Pulmonary Associates Recruiting
Louisville, Kentucky, United States, 40202
Contact: Research Coordinator    502-587-8000      
Principal Investigator: John McConnell, MD         
United States, Massachusetts
Tufts Medical Center Recruiting
Boston, Massachusetts, United States, 02111
Contact: Research Coordinator    617-636-1334      
Principal Investigator: Nicholas Hill, MD         
Boston University School of Medicine Recruiting
Boston, Massachusetts, United States, 02118
Contact: Research Coordinator    617-638-4486      
Principal Investigator: Harrison W. Farber, MD         
United States, Missouri
Washington University School of Medicine Recruiting
St. Louis, Missouri, United States, 63110
Contact: Research Coordinator    314-747-8174      
Principal Investigator: Murali Chakinala, MD         
United States, Ohio
Lindner Center for Research & Education at The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Research Coordinator    513-585-1777      
Principal Investigator: Peter Engel, MD         
University of Cincinnati Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Research Coordinator       roadst@ucmail.uc.edu   
Principal Investigator: Jean Elwing, MD         
Mercy Health Physicians Cincinnati, LLC Recruiting
Fairfield, Ohio, United States, 45014
Contact: Research Coordinator       mdclifford@health-partners.org   
Principal Investigator: Lynne Wagoner, MD         
United States, Oregon
Legacy Medical Group - Pulmonary Clinic Recruiting
Portland, Oregon, United States, 97210
Contact: Research Coordinator       tmayfiel@lhs.org   
Principal Investigator: Catherine Markin, MD         
United States, Pennsylvania
The Heart Group of Lancaster General Hospital Recruiting
Lancaster, Pennsylvania, United States, 17603
Contact: Research Coordinator       LAKruse@lghealth.org   
Principal Investigator: Justin Roberts, DO         
United States, Texas
UT Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: Research Coordinator    214-645-6489      
Principal Investigator: Fernando Torres, MD         
BreatheAmerica El Paso, Inc. Recruiting
El Paso, Texas, United States, 79912
Contact: Research Coordinator    615-665-7130      
Principal Investigator: Hernando Garcia, MD         
Sponsors and Collaborators
Reata Pharmaceuticals, Inc.
  More Information

No publications provided

Responsible Party: Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02036970     History of Changes
Other Study ID Numbers: RTA 402-C-1302
Study First Received: January 13, 2014
Last Updated: June 30, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Reata Pharmaceuticals, Inc.:
Pulmonary Arterial Hypertension
PAH
Bardoxolone methyl
6-minute walk distance
CDDO-me
RTA 402

Additional relevant MeSH terms:
Hypertension, Pulmonary
Hypertension
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 22, 2014