Safety, Tolerability, and Pharmacokinetics of a New Formulation of Nemiralisib Administered via a Dry Powder Inhaler to Healthy Individuals.

PURPOSE: Nemiralisib, a phosphoinositide 3-kinase δ inhibitor, is being investigated as an immunomodulatory agent with anti-inflammatory properties in chronic obstructive pulmonary disease. This study evaluated the pharmacokinetic (PK) properties and safety of a new formulation of nemiralisib that contains 0.4% magnesium stearate.

METHODS: In this randomized, double-blind, parallel-group study, healthy individuals received a single dose of 500 or 750 μg of nemiralisib administered via the Ellipta dry powder inhaler (DPI) (n = 6 in each treatment group). Aerodynamic particle size distribution (APSD) data comparing previous and new formulations were available before the study. Serial PK analyses for plasma exposure and safety assessments were performed during the first 24 h after dosing, with follow-up measurements on days 3 and 6 in clinic.

FINDINGS: APSD had increases of approximately 6-fold and 2-fold in very fine particle mass and fine particle mass over the previous (Diskus) formulation. In humans, systemic exposure (AUC) was greater after inhalation of 750 versus 500 μg of nemiralisib (AUC0-t : 17,200 h∙pg/mL; 95% CI, 10,900-27,200 h∙pg/mL and 13,100; 95% CI, 8130-21,000 h∙pg/mL, respectively). A low frequency of individual adverse events and no serious adverse events were reported after both doses.

IMPLICATIONS: After single-dose inhalation of 500 and 750 μg of nemiralisib from the Ellipta DPI in healthy individuals, plasma PK data were well defined, and as predicted based on previous PK and APSD data, exposure was increased with the new formulation. Nemiralisib was well tolerated with no new safety issues identified. These data supported progression of nemiralisib to a Phase IIb study in patients with chronic obstructive pulmonary disease. ClinicalTrials.gov identifier: NCT03189589.