Safety and tolerability of treprostinil palmitil inhalation powder (TPIP) in pulmonary hypertension associated with interstitial lung disease (PH-ILD)

Objective: This phase 2, double-blind, placebo-controlled trial (NCT05176951) evaluated safety and tolerability of TPIP in patients with PH-ILD over 16 weeks. Methods: Patients were randomized 3:1 to TPIP or placebo dry powder inhalation once-daily, titrated from 80 μg to the maximum tolerated dose, up to 640 μg. Primary endpoints were adverse events (AEs), serious AEs (SAEs), and change in oxygenation during 6-min walk test (6MWT). Secondary endpoints (pharmacokinetics [PK]) and exploratory endpoints were assessed. Results: 39 patients were randomized (TPIP n=29; placebo n=10); 30 (76.9%) completed treatment. Baseline characteristics were generally balanced except for gender. TPIP maximum dose (640 μg) was achieved by 79.3% of patients. AEs occurred in 27 (93.1%) vs 9 (90.0%) patients with TPIP vs placebo; most frequent were cough, diarrhea, and dyspnea and most AEs were mild/moderate. SAEs occurred in 6 (20.7%) vs 4 (40.0%) patients with TPIP vs placebo; there were 2 deaths in each group. No SAE/death was assessed as treatment-related. AEs leading to treatment discontinuation were less frequent with TPIP (13.8%) vs placebo (30.0%). There were no meaningful changes from baseline in oxygenation at 6MWT or in supplemental oxygen use with TPIP or placebo. The TPIP PK profile supports once-daily dosing. At week 10 following TPIP 480 μg and 640 μg, the treprostinil median T max , mean C max , AUC Ƭ, and t 1/2 were 1.03 and 1.46 h, 1246 and 1594 pg/mL, 4675 and 7510 pg*h/mL and 7.28 and 7.10 h, respectively. Exploratory endpoints: Clinical worsening occurred in 3 (10.3%) vs 5 (50.0%) patients with TPIP vs placebo (nominal P =0.0164). Placebo-corrected median change from baseline in the 6MWT distance with TPIP was 30 m (95% CI -49 to 171; nominal P =0.348). Conclusion: TPIP was generally well tolerated, with the maximum dose (640 μg) achieved by most patients. AEs were consistent with inhaled prostacyclin therapy. Funding This study was funded by Insmed Incorporated. Publication History Article published online: 04 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany