This article is part of Pulmonology Advisor‘s coverage of the American Thoracic Society International Conference, taking place in Dallas, Texas. Our staff will report on medical research related to asthma and other respiratory conditions, conducted by experts in the field. Check back regularly for more news from ATS 2019.
DALLAS — Use of the dry powder formulation of treprostinil, known as LIQ861, has demonstrated safety and tolerability in patients with pulmonary arterial hypertension (PAH) beyond 2 weeks. The phase 3 open-label multicenter Investigation of the Safety and Pharmacology of Dry Powder Inhalation of Treprostinil (INSPIRE) study (ClinicalTrials.gov Identifier: NCT03399604) was conducted and the results were presented at the American Thoracic Society International Conference held May 17-22, in Dallas, Texas.
The primary objective of the INSPIRE study was to evaluate the long-term safety and tolerability of LIQ861 in patients with PAH. The secondary study objective was to assess the relative bioavailability of treprostinil by comparing LIQ861 with the treprostinil inhalation solution.
Enrollment in the INSPIRE study was conducted across 2 cohorts: prostacyclin (PGI)-naive participants who were stable on ≤2 approved non-PGI oral therapies for the treatment of PAH (add-on group) and participants who were transitioning from the treprostinil inhalation solution (transition group). A minimum of 18 patients treated with treprostinil inhalation solution were also included in a bioavailability substudy that compared treprostinil exposure in a one-directional crossover study.
In all participants, treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), clinical laboratory values, physical examination findings, and vital signs were evaluated at week 2, month 1, and month 2, with bimonthly follow-ups until regulatory approval of LIQ861. Results of the treatment transition from treprostinil inhalation solution were reported at month 2.
Among the exploratory end points investigated were 6-minute walk distance, New York Heart Association Functional Class (NYHA FC), quality of life, and N-terminal B-type natriuretic peptide levels, with data collected through month 4.*
A total of 109 participants were enrolled in the study, with 65 in the add-on group and 44 in the transition group. At baseline, 66.1% of patients (72 of 109) were NYHA FC II and 33.9% of participants (37 of 109) NYHA FC III. At week 2, LIQ861 doses up to approximately 125 mcg were assessed, with no dose-limiting toxicities or study drug–related SAEs observed. Of the TEAEs reported, most were mild and consistent with the use of inhaled PGI therapy. The most commonly reported TEAEs with LIQ861 therapy in ≥4% of patients with PAH were cough (25%), headache (13%), throat irritation (12%), diarrhea (7%), dizziness (6%), chest discomfort (5%), and oropharyngeal pain (5%).
The first patient was treated in March 2018. At month 2, 95.4% of participants (42 of 44) in the transition group remained on LIQ861. No study drug-related SAEs have been reported through 10 months of follow-up.
The investigators concluded that treatment with LIQ861, the dry powder formulation of treprostinil, is safe and well tolerated in patients with PAH.
*The preliminary results from the bioavailability study will be reported at the time the abstract is presented.
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Hill NS, Feldman JP, Sahay S, et al. 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 Tresprostinil NCT03399604). Presented at: the American Thoracic Society International Conference; May 21, 2019; Dallas, TX. Abstract A7402/P1155.