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Phase 1 Study Results of LIQ861, an Inhaled Dry Powder Formulation of Treprostinil

Robert Rosigno

Toby Vaughn

William Wargin

R. Williams

C Forsythe

T Hunt

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Conference: 2018 PHA International PH Conference & Scientific Sessions

Release Date: 06.28.2018

Presentation Type: Abstracts

File Download: Conference 2018_1057

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2018 International PH Conference and Scientific SeAbstract presented at the 2018 International PH Conference and Scientific Sessions in Orlando, Fla., June 28-July 1, 2018.

Purpose

Treprostinil (Tre) is a synthetic analog of prostacyclin approved for inhalation administration to patients with pulmonary arterial hypertension (PAH) via nebulized Tyvaso® Inhalation Solution (Tre Solution) administered four times daily. The time required for nebulizer preparation, administration and cleaning is a burden to patients. Liquidia is developing LIQ861, a convenient, inhaled dry powder formulation of Tre that offers a simple, portable alternative treatment regimen.

Background

LIQ861 is specifically designed to improve the therapeutic profile of Tre by enhancing deep lung delivery and achieving higher dose levels than current inhaled therapies. Using our proprietary PRINT® technology, LIQ861 particles are a precise, uniform size (1 µm) and trefoil pollen-like shape. Liquidia conducted a Phase 1 randomized, double-blind, placebo-controlled, single ascending dose study in 57 healthy adult subjects who received 25 mcg to 150 mcg in two inhalations per capsule using an approved “off-the-shelf” dry powder inhaler (DPI) device (RS00 Model 8, Plastiape SpA, Lecco, Italy). The study’s primary objectives were to characterize Tre PK, evaluate the safety and tolerability of inhaled LIQ861 and assess the performance of the DPI.

Methods

Successive gender-balanced cohorts of 8 healthy volunteers were randomly assigned to active (n=6) or placebo (n=2). Dosing was initiated in the first cohort at a dose level of 25 mcg treprostinil. Additional cohorts of 8 subjects were enrolled to investigate escalating single doses of LIQ861 at 50, 75, 100, 125, and 150 mcg Tre. PK samples and safety assessments were performed pre- and post-dose administration. A Safety Review Committee was consulted after each cohort to review safety findings and interim PK results. Tre PK parameters and dose proportionality were characterized.

Results

LIQ861 was generally well-tolerated at all dose levels in the study. No dose limiting toxicity was observed and no SAEs were reported. No notable or significant findings were reported with vital signs, physical examinations and laboratory evaluations. The median Tre Tmax was between 10 and 20 min post-dose and both Cmax and AUCinf tended to dose proportionality.

Conclusions

LIQ861 was well-tolerated at Tre doses up to 150 mcg with no SAEs and only mild AEs. Tre exposure (Cmax& AUCinf) from LIQ861 was dose proportional from 25 to 150 mcg. At higher doses, 50% of subjects had measurable Tre at 4 hrs. No dose limiting toxicity was observed and the maximum tolerated dose (MTD) was not reached. Currently, a Phase 3 study titled “Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil (INSPIRE)” evaluating LIQ861 in patients with PAH is in progress (NCT03399604).