American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Feb 2025
Randomized Controlled Trial Multicenter StudyEfficacy and Safety of Admilparant, an LPA1 Antagonist in Pulmonary Fibrosis: A Phase 2 Randomized Clinical Trial.
Rationale: Idiopathic pulmonary fibrosis (IPF) and progressive pulmonary fibrosis (PPF) have high morbidity and mortality; thus, novel treatments are needed. Objectives: Assess efficacy and safety of admilparant (BMS-986278), an oral lysophosphatidic acid receptor 1 antagonist, in patients with IPF and PPF. Methods: This phase 2, randomized, double-blind, placebo-controlled trial included parallel cohorts of patients with IPF (n = 278 randomized, n = 276 treated) or PPF (n = 125 randomized, n = 123 treated) who received 30 mg of admilparant, 60 mg of admilparant, or placebo (1:1:1) twice daily for 26 weeks. ⋯ Treatment discontinuations because of adverse events were similar across IPF arms and lower with admilparant (2.5% [30 mg]; 0% [60 mg]) versus placebo (17.1%) for PPF. Conclusions: In this first phase 2 study to evaluate antifibrotic treatment in parallel IPF and PPF cohorts, 60-mg admilparant slowed lung function decline and was safe and well tolerated, supporting further evaluation in phase 3 trials. Clinical trial registered with clinicaltrials.gov identifier (NCT04308681).
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Am. J. Respir. Crit. Care Med. · Feb 2025
Randomized Controlled TrialEffect of Triple Therapy on Cardiovascular and Severe Cardiopulmonary Events in COPD: A Post-hoc Analysis of a Randomized, Double-Blind, Phase 3 Clinical Trial (ETHOS).
Rationale: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular and cardiopulmonary events. In the phase III, 52-week ETHOS trial (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) reduced rates of moderate/severe exacerbations and all-cause mortality compared with dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. ⋯ Time to first severe COPD exacerbation was a prespecified endpoint; post hoc cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event, time to first cardiovascular adverse event (AE) of special interest, time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. Measurements and Main Results: BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for time to first cardiovascular adverse event of special interest (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). Conclusions: BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate to very severe COPD.