An Evaluation of the Pharmacokinetics, Safety, and Tolerability of Aclidinium/Formoterol Fixed-Dose Combination Administered in Chinese Patients with Moderate-to-Severe Chronic Obstructive Pulmonary Disease

Hong Zhang, Sami Z Daoud, Michael S Gillen, Natalia Calderon, Maria Heijer, Eduard Molins, Esther Garcia-Gil, Hong Chen, Qianqian Li, Chengjiao Liu, Yanhua Ding, Hong Zhang, Sami Z Daoud, Michael S Gillen, Natalia Calderon, Maria Heijer, Eduard Molins, Esther Garcia-Gil, Hong Chen, Qianqian Li, Chengjiao Liu, Yanhua Ding

Abstract

Background and objectives: The aim of this study was to evaluate the pharmacokinetics, safety, and tolerability of aclidinium bromide/formoterol fumarate in patients from China with moderate-to-severe chronic obstructive pulmonary disease (COPD).

Methods: In this open-label, repeat-dose, 5-day pharmacokinetic study (NCT03276078) of inhaled aclidinium bromide/formoterol fumarate 400/12 µg twice daily, plasma concentrations of aclidinium, formoterol, and two aclidinium metabolites (LAS34823, LAS34850) were assessed (days 1 and 5). Adverse event (AE) data were collected.

Results: Twenty patients (15 [75%] males) with a mean age of 59.2 years were included. Median (range) time to maximum concentration on days 1 and 5 was 0.08 (0.08-0.50) and 0.08 (0.08-0.50) h, respectively, for aclidinium; and 1.00 (0.08-3.00) and 0.08 (0.08-1.50) h, respectively, for formoterol. Mean elimination half-life and accumulation ratio for area under the concentration-time curve during a dosage interval (AUCτ) was 19.42 h and 2.0, respectively, for aclidinium; and 14.06 h and 1.4, respectively, for formoterol. Steady-state maximum concentration (Cmax,ss) and AUCτ on day 5 were 60.86 pg/mL and 168.80 h·pg/mL, respectively, for aclidinium; and 6.47 pg/mL and 31.98 h·pg/mL, respectively, for formoterol. Aclidinium produced high coefficients of variation (day 1: AUCτ 79.0%, Cmax 84.5%; day 5: AUCτ 82.2%, Cmax 150.0%). Few AEs were reported, typically one per patient. One patient discontinued due to a serious AE (considered possibly unrelated to treatment).

Conclusions: Aclidinium/formoterol 400/12 µg twice daily was well-tolerated in patients from China with moderate-to-severe COPD. Safety findings were consistent with the known safety profile.

Clinical trial identifier: ClinicalTrials.gov, NCT03276078.

Conflict of interest statement

Sami Z. Daoud, Michael S. Gillen, Maria Heijer and Eduard Molins are employed by AstraZeneca, and Esther Garcia-Gil and Natalia Calderon are former employees of AstraZeneca. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study design. BID twice daily, D day
Fig. 2
Fig. 2
Geometric mean plasma concentrations of a aclidinium, b formoterol, c LAS34850, and d LAS34823 (pharmacokinetic analysis set). SD standard deviation

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