Efficacy and safety of a transdermal donepezil patch in patients with mild‐to‐moderate Alzheimer's disease: A 24‐week, randomized, multicenter, double‐blind, parallel group, non‐inferiority study

Aim To assess non‐inferiority of a donepezil patch 27.5 mg compared with donepezil hydrochloride tablets 5 mg in patients with mild‐to‐moderate Alzheimer's disease; and to compare the efficacy and safety profiles of a donepezil patch 27.5 mg with donepezil hydrochloride tablets 5 mg. Methods This was a 24‐week, multicenter, randomized, double‐blind, double‐dummy, parallel group, non‐inferiority (phase III) study carried out in Japan. The primary end‐point was the change in the Alzheimer's Disease Assessment Scale‐cognitive component‐Japanese version from baseline to week 24, with the aim of evaluating the non‐inferiority of the donepezil patch 27.5 mg compared with donepezil hydrochloride tablets 5 mg. Results Of 340 randomized patients, 303 completed the double‐blind period. Changes from baseline in the Alzheimer's Disease Assessment Scale‐cognitive component‐Japanese version at week 24 (least squares mean ± standard error) were −0.7 ± 0.4 (donepezil patch 27.5 mg) and 0.2 ± 0.4 (donepezil hydrochloride tablet 5 mg). The difference in the least squares means (95% confidence interval) was −0.9 (−2.01 to 0.14). The upper bound of the 95% confidence interval for the difference between groups was less than the predefined non‐inferiority margin of 2.15. The donepezil patches 27.5 mg also had a safety profile that showed good tolerability comparable with donepezil hydrochloride tablets 5 mg. Conclusions Non‐inferiority on suppression of cognitive decline was shown for the donepezil patch 27.5 mg when compared with donepezil hydrochloride tablets 5 mg in Japanese patients with mild‐to‐moderate Alzheimer's disease. Geriatr Gerontol Int 2023; 23: 275–281. We assessed non‐inferiority of a donepezil patch 27.5 mg in comparison with donepezil hydrochloride tablets 5 mg in patients with mild‐to‐moderate Alzheimer's disease; and compared the efficacy and safety profiles of the donepezil patch with the donepezil hydrochloride tablets. Non‐inferiority of the patch and the tablets was shown. The patch had a safety profile with good tolerability.