Clinical use of aclidinium in patients with COPD

Figures & data

Table 1 Summary of aclidinium efficacy trials

Trial	Study design	Study duration	Intervention	Outcomes
Joos et al^Citation14	n=17 CO, DB, MC, PC, R Phase IIa	Single dose	Aclidinium 100 μg, 300 μg, 900 μg vs placebo	Significant improvements in AUC0–24/24 for aclidinium versus placebo (P<0.001)
Chanez et al^Citation15	n=464 (441 completed) AC, DB, MC, MN, PC, R Phase IIb	4 weeks	Aclidinium 25 μg, 50 μg, 100 μg, 200 μg, 400 μg daily vs placebo daily and tiotropium 18 μg daily (open label)	Significant increases in trough FEV1 at week 4 for aclidinium 200/400 μg and tiotropium compared with placebo
Vestbo et al^Citation16	n= 115 (107 completed) CO, DB, MC, MN, R Phase II	Single dose	Aclidinium 200 μg vs placebo and tiotropium 18 μg	Significant improvements in percentage of patients with FEV1 increase ≥ 10% at 30 minutes compared with placebo (P<0.0001 for both medications) Significant improvements in mean change in FEV1 at 30 minutes: + 122 mL aclidinium, +118 mL tiotropium, +27 mL placebo (P<0.0001 for both compared with placebo) Significant improvements in FVC, IC, and perception of dyspnea
Jones et al^Citation17 ACCLAIM/COPD I	n=843 (707 completed) R, DB, PC, MC, MN Phase III	52 weeks	Aclidinium 200 μg daily vs placebo	Significant increase in trough FEV1 at 12/28 weeks Range +37–67 mL throughout the study Significantly more aclidinium patients achieved the MCID for SGRQ at week 52; mean difference in SGRQ at 52 weeks −4.63 aclidinium, −3.1 placebo (P=0.19) Significantly more aclidinium patients achieved the MCID for TDI at week 52; mean difference in TDI at 52 weeks + 1.83 aclidinium, +0.61 placebo (P<0.000l)
Jones et al^Citation17 ACCLAIM/COPD II	n=804 (564 completed) R, DB, PC, MC, MN Phase III	52 weeks	Aclidinium 200 μg daily vs placebo daily	Significant increase in trough FEV1 at 12/28 weeks Range +51–78 mL throughout the study Significantly more aclidinium patients achieved the MCID for SGRQ at week 52; mean difference in SGRQ at 52 weeks −3.49 aclidinium, −1.28 placebo (P=0.021) Nonsignificantly more aclidinium patients achieved the MCID for TDI at week 52; mean difference in TDI at 52 weeks + 1.61 aclidinium, +1.09 placebo (P=0.12) Fewer patients in aclidinium group compared with placebo group experienced a moderate to severe COPD exacerbation (33.2% vs 39.8%, P=0.0046)
Fuhr et al^Citation11	n=30 (27 completed) AC, CO, DB, MC, PC, R Phase IIa	15 days	Aclidinium 400 μg BID vs placebo and tiotropium 18 μg daily	Mean change in FEV1 AUC0–12/12h was significantly higher in the aclidinium and tiotropium groups than placebo (P<0.0001) Significant differences between aclidinium and tiotropium existed for FEV1 AUC12–24/24h and FVC AUC12–24/24h COPD symptoms significantly improved with aclidinium but not with tiotropium compared with placebo
Singh et al^Citation18	n=79 (68 completed) AC, CO, DB, MC, MN, PC, R Phase IIb	7 days	Aclidinium 100 μg, 200 μg, 400 μg BID vs placebo and formoterol 12 μg BID	Significant improvements in FEV1 AUC0–12 in both active medication groups compared with placebo (P<0.0001)
Jones et al^Citation19 ATTAIN	n=828 (737 completed) DB, MC, MN, PC, R Phase III	24 weeks	Aclidinium 200 μg, 400 μg BID vs placebo	Significant improvements in trough FEV1 compared with placebo at week 24: +99 mL aclidinium 200 μg, +128 mL aclidinium 400 μg(P<0.000l for both) Significant improvements in SGRQ compared with placebo at week 24: −3.8 units aclidinium 200 μg (P<0.001), −4.6 units aclidinium 400 μg (P<0.0001) Significant improvements in TDI at week 24 compared with placebo: +0.6 units aclidinium 200 μg (P<0.05), +1 unit aclidinium 400 μg (P<0.001)
Kerwin et al^Citation20 ACCORD I	n=561 (467 completed) DB, MC, MN, PC, R Phase III	12 weeks	Aclidinium 200 μg, 400 μg BID vs placebo	Statistically significant improvements in trough FEV1 at week 12 for aclidinium 200 μg (+86 mL, P<0.0001). Clinically and statistically significant improvements in FEV1 at week 12 for aclidinium 400 μg (+124 mL, P<0.0001) Significant improvements in TDI, SGRQ, and symptom scores at week 12
D’Urzo et al^Citation21	n=291 (199 completed) DB, MC, MN, R Phase III extension	52 weeks	Aclidinium 200 μg, 400 μg BID	Clinically and statistically significant improvements in SGRQ from baseline in all groups Improvements in trough and peak FEV1
Rennard et al^Citation22 ACCORD II	n=544 (454 completed) DB, PC, MC, MN, R Phase III	12 week	Aclidinium 200 μg, 400 μg BID vs placebo	Statistically but not clinically significant improvements in FEV1 at week 12: +51 mL aclidinium 200 μg, +72 mL aclidinium 400 μg Numerically higher results in SGRQ from baseline in both groups compared with placebo Statistically significant improvements in TDI from baseline
Beier et al^Citation23	n=414 (400 completed) Phase IIIb AC, DB, MC, MN, PC, R	6 weeks	Aclidinium 400 μg BID vs placebo and Tiotropium 18 μg daily	Statistically significant improvements in FEV1 AUC0–24 at week 6 in both active treatments compared with placebo Statistically significant improvements in E-RS compared with placebo in both active treatment arms
Gelb et al^Citation24	n=605 (341 completed) DB, R	52 weeks	Aclidinium 200 μg, 400 μg BID	Numerical improvements in trough FEV1 compared with baseline Clinically significant improvements in SGRQ compared with baseline

Abbreviations: AC, active comparator; ACCLAIM/COPD, Aclidinium Clinical Trial Assessing Efficacy and Safety in Moderate to Severe COPD Patients; ACCORD, Aclidinium in Chronic Obstructive Respiratory Disease; ATTAIN, Aclidinium to Treat Airway Obstruction in COPD Patients; BID, twice daily; CO, crossover; DB, double blind; E-RS, EXACT (exacerbations of chronic pulmonary disease tool)-Respiratory Symptoms; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; IC, inspiratory capacity; MC, multicenter; MCID, minimal clinically important difference; MN, multinational; O, open label; PC, placebo controlled; R, randomized; SGRQ, St George’s Respiratory Questionnaire; TDI, Transitional Dyspnea Index.

Table 2 Patient satisfaction with Pressair™/Genuair™ versus HandiHaler devices

Parameter	Beier et al,^Citation23 n=414 Patient preference (%)		Van der Palen et al,^Citation35 n=105 Patient preference (%)
	Pressair/Genuair	HandiHaler	Pressair/Genuair	HandiHaler
Ease of use	86.7*	9.0	83.9*	16.1
Convenience	87.4*	7.8	79.8*	20.2
Ease of learning	79.1*	8.0	82.4*	17.6
Ease of holding	79.9*	8.5	85.4*	14.6
Ease of operation	81.1*	9.2	84.5*	15.5
Ease of dose preparation	86.4*	7.8	87.6*	12.4
User feedback	76.2*	9.5	69.2**	30.8

Notes:

* P<0.0001

** P<0.01 compared with HandiHaler.

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