A Phase 2 Study of the Safety and Tolerability of Treprostinil Palmitil Inhalation Powder in Patients With Pulmonary Hypertension Associated With Interstitial Lung Disease

Colin Church, Maria Molina-Molina, Miguel Arias-Guillén, Patrick Muchmore, Ben R. Lavon, Jan De Backer, Natalya Makulova, Bipin Mistry, Jia Guo, Jasmanda Wu, Junaideen Fahumy, Ariel Teper, Peng-Liang Zhao, Kevin C. Mange, Gerald O'Brien

https://doi.org/10.1002/pul2.70322 

Abstract

Treprostinil palmitil (TP) inhalation powder (TPIP), an investigational formulation of the treprostinil prodrug TP, was designed to provide prolonged pulmonary vasodilation with once-daily administration. In this phase 2 study (NCT05176951), adults with pulmonary hypertension associated with interstitial lung disease (PH-ILD) were randomized 3:1 to receive TPIP (n = 29) or placebo (n = 10) for 16 weeks. TPIP was up-titrated from 80 µg to each patient's maximum tolerated dose (≤ 640 µg). Study endpoints were safety and tolerability (primary); pharmacokinetics of TP and treprostinil (secondary); and clinical worsening, change from baseline in 6-min walk distance (6MWD), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (exploratory). Maximum TPIP dose (640 µg) once daily was achieved by 79.3% of patients. TPIP was well tolerated in this study, with a safety profile generally consistent with previously reported route-specific treatment-emergent adverse events (TEAEs) of inhaled treprostinil, such as cough and dyspnea. TEAEs occurred in 93.1% and 90.0% of patients on TPIP and placebo, respectively. Most TEAEs were mild or moderate in both groups. In patients on TPIP and placebo, TEAEs leading to treatment discontinuation occurred in 4 (13.8%) and 3 (30.0%) patients, respectively, and serious AEs occurred in 6 (20.7%) and 4 (40.0%) patients, respectively. Following the 640 µg TPIP dose, the treprostinil elimination half-life was 7.1 h. In TPIP and placebo groups, clinical worsening was observed in 3 (10.3%) and 5 (50.0%) patients, respectively. Trends for improvement were observed in 6MWD and NT-proBNP with TPIP treatment. These results suggest that TPIP may be a suitable once-daily treatment for PH-ILD.

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