A Randomized Comparison of the Pharmacokinetics and Bioavailability of Fluticasone Propionate Delivered via Xhance Exhalation Delivery System Versus Flonase Nasal Spray and Flovent HFA Inhalational Aerosol.

PURPOSE: The exhalation delivery system with fluticasone propionate (Xhance®) has been shown to deliver drug substantially more broadly in the nasal cavity (particularly into superior/posterior regions), with less off-target loss of drug to drip-out and swallowing, than conventional nasal sprays. This open-label study evaluated the systemic bioavailability of Xhance® by comparing the pharmacokinetic (PK) properties of a single dose of fluticasone from 3 products administering the drug using 3 different devices: Xhance®, Flonase® (fluticasone propionate inhalational nasal spray), and Flovent® HFA (fluticasone propionate inhalational aerosol).

METHODS

This open-label study was conducted in 2 parts. Study part 1 compared systemic exposure with a single dose of Xhance® 186 or 372 μg versus Flonase® 400 μg (3-way, 3-treatment, 3-sequence, randomized crossover in healthy subjects; n = 90). A separate study, part 2, under the same umbrella protocol, compared systemic exposure with Xhance® 372 μg versus Flovent® HFA 440 μg (2-way, 2-treatment, 2-sequence, randomized crossover in patients with mild to moderate asthma; n = 30).

FINDINGS: With Xhance® 186 μg, the geometric least squares mean (LSM) Cmax was higher than with Flonase® 400 μg (16.02 vs 11.66 pg/mL, respectively; geometric mean ratio [GMR], 137.42%) and the geometric LSM AUC0-∞ values were similar (97.30 vs 99.61 pg · h/mL; GMR, 97.78%). With Xhance® 372 μg, the geometric LSM Cmax and AUC0-∞ were higher than with Flonase® 400 μg (Cmax, 23.50 vs 11.66 pg/mL [GMR, 201.53%]; AUC0-∞, 146.61 vs 99.61 pg · h/mL [GMR, 147.19%]). In part 2, the geometric LSM Cmax and AUC0-∞ values were lower with Xhance® 372 μg than with Flovent® HFA 440 μg (Cmax, 25.28 vs 40.02 pg/mL [GMR, 63.18%]; AUC0-∞, 205.78 vs 415.16 pg · h/mL [GMR, 49.57%]).

IMPLICATIONS: Similar intranasal doses of Xhance® (372 μg) and Flonase® (400 μg) are clearly not bioequivalent. Systemic exposure is very low with all products. Systemic exposure is higher with Xhance® than with Flonase® and substantially lower than with Flovent® HFA 440 μg and, based on dose normalization, Flovent® HFA 220 μg. ClincalTrials.gov identifier: NCT02266927.