Lti-201: Evaluation Of The Hemodynamics And Safety Of Inhaled Liq861 (Treprostinil) In Pulmonary Arterial Hypertension (Who Group 1) Patients

Introduction: LIQ861 is a novel, dry-powder formulation of treprostinil (TRE) designed with PRINT® technology to enhance deep-lung drug deposition and enable delivery of TRE in 1-2 breaths per capsule 4 times per day (QID) with a convenient dry-powder inhaler (DPI). Aims and Objectives: Study aims are to characterize hemodynamic dose-response relationships for LIQ861 and to evaluate the safety of LIQ861 in patients with pulmonary arterial hypertension (PAH). Methods: LTI-201 is a European open-label, phase 2 study with a dose-escalation phase (Part A) and 16 weeks of continuous administration of LIQ861 (Part B). Eligibility criteria include New York Heart Association functional class II-IV; six-minute walk distance ≥150 m; forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) ≥60% of predicted values; and FEV1/FVC ratio ≥60%. Planned enrollment is 32 patients at 2 centers. During Part A, 4 successive cohorts (n=8 each) will receive LIQ861 in a 25, 50, 75, and 100 µg capsule-strength dose using the Plastiape RS00 Model 8 DPI device. Safety results will be reviewed before proceeding to the next dose. During Part B, PAH patients will receive LIQ861 from Day 1 through Week 16. Results: The primary efficacy endpoint is the change in pulmonary vascular resistance from baseline to maximal response on Day 1 (Part A) and Week 16 (Part B). Additional hemodynamic endpoints and pharmacokinetic parameters will be assessed during Parts A and B. The primary safety endpoint is the incidence of adverse events and SAEs in Parts A and B. Conclusion: LTI-201 will assess the pharmacokinetics, safety, and efficacy of LIQ861 in PAH patients.