The LARIAT Trial is a clinical research trial targeting the Non Specific Interstitial Pneumonia (NSIP) patient population. Please click on the pin nearest to your geographic location to learn more about investigational sites in your area.
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The LARIAT Trial is a clinical research trial targeting the Non Specific Interstitial Pneumonia (NSIP) patient population. Please click on the city nearest to your geographic area to inquire about the LARIAT Trial.
University of California – Davis Medical Center, Sacramento, CA
University of Colorado Denver, Aurora, CO
University of Texas Southwestern Medical Center, Dallas, TX
Washington University School of Medicine, St. Louis, MO
South Denver Cardiology Associates, Littleton, CO
University of California San Francisco, San Francisco, CA
Winthrop University Hospital, Mineola, NY
University of Cincinnati, Cincinnati, OH
The Lindner Clinical Trial Center, Cincinnati, OH
Boston University School of Medicine, Boston, MA
Arizona Pulmonary Specialists, Phoenix, AZ
Houston Methodist Hospital, Houston, TX
BreatheAmerica, El Paso, TX
University of Chicago, Chicago, IL
Tufts Medical Center, Boston, MA
Kentuckiana Pulmonary Associates, Louisville, KY
Harbor UCLA Medical Center, Torrance, CA
The University of Texas, Houston, TX
Cleveland Clinic of Florida, Weston, FL
Lancaster General Hospital, Lancaster, PA
VA Healthcare System of Greater Los Angeles, Los Angeles, CA
The Ohio State University Wexner Medical Center, Columbus, OH
Beth Israel Medical Center, New York City, NY
Cedars-Sinai Medical Center, Beverly Hills, CA
Brigham and Women’s Hospital, Boston, MA
University of Rochester, Rochester, NY
Maine Medical Center, Portland, ME
Stanford University School of Medicine, Stanford, CA
Aurora St. Luke’s Medical Center, Milwaukee, WI
Pulmonary and Critical Care of Atlanta, Atlanta, GA
Diagnamics Inc, Encinitas, CA
Weill Cornell Medical Center, New York, NY
The Iyer Clinic, Herndon, VA
University of Utah, Salt Lake City, UT
Banner Health Research Institute, Phoenix, AZ
Georgetown University Medical Center , Washington, DC
Purpose
| Condition | Intervention | Phase |
|---|---|---|
| Pulmonary 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 Hypertension |
Primary Outcome Measures:
- Change from baseline in 6-Minute Walk Distance (6MWD) [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 208 |
| Study Start Date: | May 2014 |
| Estimated Study Completion Date: | December 2016 |
| Estimated Primary Completion Date: | September 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Dose-Ranging Phase: 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: Dose-Ranging Phase: 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: Dose-Ranging Phase: 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 |
| Experimental: Dose-Ranging Phase: 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 |
| Experimental: Dose-Titration Phase
Bardoxolone methyl [Dose 2] mg capsules or placebo by mouth once daily x 3 weeks, escalating to [Dose 3] mg or placebo by mouth once daily at Week 4 for 13 weeks If a patient experiences a dose-limiting toxicity, the investigator may de-escalate the dose. |
Drug: Bardoxolone methyl
Other Name: RTA 402 capsules
Drug: Placebo |
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.
Eligibility
| Ages Eligible for Study: | 18 Years to 75 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Adult male and female patients ≥ 18 to ≤ 75 years of age upon study consent;
- BMI > 18.5 kg/m²
- Symptomatic pulmonary hypertension WHO class II and III;
WHO Group I, III, or V PH according to the following criteria:
a. If diagnosed with WHO Group I PH, then on of the following subtypes:
i. Idiopathic or heritable PH;
ii. PH associated with connective tissue disease;
iii. PH associated with simple, congenital systemic-to-pulmonary shunts at least 1 year following shunt repair;
iv. PH associated with anorexigen or drug-induced toxicity;
v. PH 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 (IPF);
iii. Nonspecific interstitial pneumonia (NSIP); or
c. If WHO Group V PH then patient must be diagnosed with sarcoidosis;
i. Had a diagnostic right heart catheterization performed and documented within 36 months prior to Day 1 that confirmed a diagnosis of PH
ii. If WHO Group I, has been receiving no more than three (3) FDA-approved disease-specific PH therapies except for intravenous (iv) prostacyclin/prostacyclin analogues. PH therapy must be at a stable dose for at least 90 days prior to Day 1;
iii. 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:
- 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;
- 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;
- Stopped receiving any PH chronic therapy within 60 days prior to Day 1;
- Requirement for receipt of intravenous inotropes within 30 days prior to Day 1;
- 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;
- Has systolic BP < 90 mm Hg during Screening after a period of rest;
- 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%;
- 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:
i. Congenital or acquired valvular disease if clinically significant apart from tricuspid valvular insufficiency due to pulmonary hypertension;
ii. Pericardial constriction;
iii. Restrictive or congestive cardiomyopathy;
iv. Left ventricular ejection fraction < 40% per echocardiogram (ECHO) within 60 days of Day 1;
v. 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 PH, any of the following:
i. Concomitant active opportunistic infections within 180 days prior to Screening;
ii. Detectable viral load within 90 days prior to Screening;
iii. Cluster designation (CD+) T-cell count < 200 mm3 within 90 days prior to Screening;
iv. Changes in antiretroviral regimen within 90 days prior to Screening;
v. Using inhaled pentamidine;
This information was originally posted on www.clinicaltrials.gov.