SESSION TITLE: COPD Treatment Posters
SESSION TYPE: Original Investigation Poster
PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM
PURPOSE: To evaluate the pharmacokinetics (PK), safety, and tolerability of aclidinium 400µg/formoterol 12µg fixed-dose combination (FDC) via Pressair®/Genuair®* and formoterol (FOR) 12µg via Foradil® Aerolizer® in patients with moderate to severe chronic obstructive pulmonary disease (COPD).
METHODS: In this Phase 2a, randomized, open-label, 2-way crossover study, 24 patients (male and female) were randomized to 1 of 2 treatment sequences with FDC via Pressair® or FOR via Aerolizer® administered twice daily for 4 days followed by 1 morning inhalation on day 5 and a 7-day washout. Plasma samples were analyzed using validated LC-MS/MS. Cmax and AUC for FOR were compared using ANCOVA. Safety also was evaluated.
RESULTS: All 24 patients completed the study. Following single-dose administration of Pressair® and Aerolizer®, mean FOR Cmax was 9.55 and 8.23pg/mL; mean AUC0-τ was 42.27 and 41.63pg•h/mL. Median FOR tmax was shorter with Pressair® than Aerolizer® (0.38 vs 1.0h). Mean day 1 FOR t½ and Day 5 FOR AUC0-τ,ss, Cmin,ss, Cavg,ss and t½ were comparable between devices. Mean FOR Cmax,ss was numerically greater with Pressair® than Aerolizer® (16.72 vs 14.90pg/mL); 90% CIs for the geometric means ratio (Pressair®/Aerolizer®) for Cmax,ss and AUC0-τ,ss were within 80%-125%. Mean steady-state FOR accumulation ratios were comparable between inhalers. Following single-dose FDC administration, mean aclidinium (ACL) Cmax and AUC0-τ were 101.98pg/mL and 228.30pg•h/mL. In most patients, ACL tmax was achieved 5 min post-dose, mean ACL t½ was ~5h. Day 5 mean ACL Cmax,ss and AUC0-τ,ss were 128.43pg/mL and 404.25pg•h/mL. Mean steady-state ACL accumulation ratio (1.38) was expected due to its ~5h half-life. Six (25.0%) FDC patients and 2 (8.3%) FOR patients reported a total of 11 treatment-emergent adverse events, none led to discontinuation.
CONCLUSIONS: Aclidinium steady state was reached following 5 days of twice daily administration via Pressair® inhaler. Formoterol steady-state was achieved within 5 days regardless of inhaler type. Formoterol PK is bioequivalent between Pressair® and Aerolizer®. All treatments were well tolerated.
CLINICAL IMPLICATIONS: PK and safety of aclidinium/formoterol FDC via Pressair® and formoterol via Aerolizer® are similar. *Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the USA as Pressair® and Genuair® within all other licensed territories. This study was funded by Almirall S.A. and by Forest Research Institute, Inc., a wholly owned subsidiary of Forest Laboratories, Inc.
DISCLOSURE: Stephan Ortiz: Employee: Forest Research Institute The following authors have nothing to disclose: Charles Fogarty
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