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 (AUC_τ) was 19.42 h and 2.0, respectively, for aclidinium; and 14.06 h and 1.4, respectively, for formoterol. Steady-state maximum concentration (C_max,ss) and AUC_τ 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: AUC_τ 79.0%, C_max 84.5%; day 5: AUC_τ 82.2%, C_max 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.