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.
Church et al. (Wed,) studied this question.