NCT02036970

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

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

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 166 (actual)
• Sponsor: Biogen · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

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.

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 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.

Conditions

• Pulmonary Arterial Hypertension
• Pulmonary Hypertension
• Interstitial Lung Disease
• Idiopathic Interstitial Pneumonia
• Idiopathic Pulmonary Fibrosis
• Sarcoidosis
• Respiratory Bronchiolitis Associated Interstitial Lung Disease
• Desquamative Interstitial Pneumonia
• Cryptogenic Organizing Pneumonia
• Acute Interstitial Pneumonitis
• Idiopathic Lymphoid Interstitial Pneumonia
• Idiopathic Pleuroparenchymal Fibroelastosis

Interventions

Type	Name	Description
DRUG	Bardoxolone methyl
DRUG	Placebo

Timeline

• Start date: 2014-05-31
• Primary completion: 2018-01-19
• Completion: 2018-05-16
• First posted: 2014-01-15
• Last updated: 2025-06-10
• Results posted: 2021-07-23

Locations

32 sites across 2 countries: United States, Germany