Table 1.

Summary of clinical trials of aclidinium bromide in humans

Study	Phase	Subjects (n)	Population	Aclidinium dose(s)*	Duration of study	Primary endpoint	Results
Schelfhout et al33	I	12 (males)	Healthy	50, 300, 600 μg, single dose with crossover	24 hours	Methacholine challenge	Significant protection against bronchoconstriction at all 3 doses.
Joos et al37	I	17 (males)	Moderate to severe COPD	100, 300, 900 μg, single dose with crossover	32 hours	FEV1 AUC0–24	Significant increase in FEV1 AUC0–24 compared with placebo. Significant and dose-dependent improvement in FEV1 2 hrs post-dose (234 for 100 μg dose; 344 mL for 300 μg dose; 377 mL for 900 μg dose).
Vestbo et al48	II	115	Moderate to severe COPD	200 μg (versus 18 μg tiotropium)	3 hours	% of subjects with ≥10% improvement in FEV1 at 30 minutes post-dose	Significant increase in % of subjects achieving ≥10% increase in FEV1 at 30 minutes for both aclidinium and tiotropium (49.5% and 51.8%, respectively, versus 13.8% for placebo). Mean % increase in FEV1 at 30 minutes for aclidinium (12%) and tiotropium (11%) both higher compared to placebo (3%).
Chanez et al34	II-b	464	Moderate to severe COPD	25, 50, 100, 200, or 400 μg daily	4 weeks	Day 29 trough FEV1	Significant improvement in day 29 trough FEV1 (148 mL for 200 μg dose; 128 mL for 400 μg dose). Significant improvement in day 29 peak FEV1 (202 mL for 200 μg dose; 204 mL for 400 μg dose). Day 29 time to peak FEV1 2 hrs versus 3 hrs for tiotropium.
Maltais et al38	III	181	Moderate to severe COPD	200 μg	6 weeks	Exercise duration during constant work rate of 75% Wmax	Significant improvement in exercise endurance relative to placebo (difference 116 ± 40 sec). Significant improvement in trough FEV1 at 6 weeks compared with placebo (difference 101 mL).
Jones et al36 (ACCLAIM I)	III	843	Moderate to severe COPD	200 μg (3:1 active to placebo)	52 weeks	Trough FEV1 at weeks 12 and 28	Statistically significant (but probably not clinically significant) improvement in trough FEV1 at 12 weeks (61 mL) and 28 weeks (67 mL). Significant difference in proportion of subjects achieving clinically significant improvement in SGRQ at all time points (48.1% versus 39.5% for placebo at 52 weeks, P = 0.025). No significant difference in exacerbation rates (26.6% versus 25.7% for placebo) or time to first exacerbation.
Jones et al36(ACCLAIM II)	III	804	Moderate to severe COPD	200 μg (3:1 active to placebo)	52 weeks	Trough FEV1 at weeks 12 and 28	Statistically significant (but probably not clinically significant) improvement in trough FEV1 at 12 weeks (63 mL) and 28 weeks (59 mL). Difference in proportion of subjects achieving clinically significant improvement in SGRQ declined over time, being significant at weeks 12, 28, and 44, but not at 52 weeks (39.0% versus 32.8% for placebo at 52 weeks, P = 0.074). Significant reduction in moderate to severe exacerbations (32.2% versus 39.8% for placebo) and in time to first exacerbation (hazard ratio 0.7 [95% CI 0.55 – 0.92], P = 0.01).

^*Note: All studies placebo-controlled.

Abbreviations: FEV₁ AUC_0–24, area under the curve of FEV₁ over 24 hours following study drug administration; SGRQ, St Georges Respiratory Questionnaire; W_max, maximum tolerated workload during baseline symptom-limited, staged (10 W increments), cycle ergometry.