INSPIRE: A Phase 3 Open-Label, Multicenter Study to Evaluate the Safety and Tolerability of LIQ861 in Pulmonary Arterial Hypertension (PAH) (Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil NCT03399604)

Abstract

Summary of Objectives Inhalational drug delivery to treat PAH is attractive due to enhanced pulmonary specificity and reduced systemic adverse effects. LIQ861 is a dry powder formulation of Treprostinil (TRE) designed to enhance deep-lung delivery and achieve higher tolerated dose levels than current inhaled therapies. LIQ861’s uniform (1µm) particle size with a trefoil, pollen-like shape, enables QID delivery of TRE doses in a convenient, palm-sized, disposable dry powder inhaler (DPI). The primary objective of the INSPIRE study is the safety and tolerability of LIQ861 in subjects transitioning from stable doses of Tyvaso® or as combination therapy with ≤2 approved non-prostacyclin (PGI) oral PAH drugs. The secondary objective is to evaluate the comparative bioavailability (BA) of TRE between LIQ861 and Tyvaso®. Methods Target enrollment is 100 Functional Class (FC) II/III subjects with 18 subjects on Tyvaso® included in a BA sub-study comparing TRE exposure in a one-directional crossover. PGI-naive subjects stable on ≤2 approved, non-PGI oral PAH therapies received LIQ861 at an initial dose of 25mcg QID, increasing in 25mcg increments weekly to tolerance and symptom relief. Subjects transitioning from Tyvaso® received LIQ861 at an initial dose comparable to their Tyvaso® dose, with titration in 25mcg QID increments to tolerance and symptom relief. Endpoints The primary endpoint is the incidence of treatment-emergent Adverse Events and Serious Adverse Events. Safety endpoints: • Changes from Baseline to Month 2 or Early Termination in clinical laboratory, physical exam findings, and vital signs. • Proportion of patients maintaining a stable clinical status from transition through Month 2. Stable clinical status defined as: 1) LIQ861 treatment through at least 2 months beyond transition from Tyvaso® and six-minute walk distance (6MWD) decrease no more than 10%, 2) no interruptions to treatment totaling more than 7 days prior to the end of Month 2, and 3) no treatment with any other PGI analogs or P`GI receptor agonists. Secondary endpoints: NYHA FC, N-terminal B-type natriuretic peptide and Quality of Life will be reported when available. Analysis for the Primary Endpoint and BA sub-study is expected to be completed in 2019.