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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2015 by Reata Pharmaceuticals, Inc.
Sponsor:
Information provided by (Responsible Party):
Reata Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT02036970
First received: January 13, 2014
Last updated: May 4, 2015
Last verified: May 2015
  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: 48
Study Start Date: May 2014
Estimated Study Completion Date: April 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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
Experimental: 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
Experimental: 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

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 dose-escalation 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. BMI > 18.5 kg/m²
  3. Symptomatic pulmonary arterial hypertension WHO/NYHA FC class II and III;
  4. 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 anorexigen or drug-induced toxicity;
    5. PAH associated with human immunodeficiency virus (HIV);
  5. Had a diagnostic right heart catheterization performed and documented within 36 months prior to Screening that confirmed a diagnosis of PAH
  6. Has been receiving at least one, but no more than two (2) 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 PAH 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. 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);
  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 31 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: May 4, 2015
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
Cardiovascular Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on May 21, 2015