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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 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: September 26, 2014
Last verified: September 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

  Show 32 Study Locations
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: September 26, 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
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 30, 2014