J Clin Neurol.  2022 Jul;18(4):428-436. 10.3988/jcn.2022.18.4.428.

A Multinational, Multicenter, Randomized, Double-Blind, Active Comparator, Phase III Clinical Trial to Evaluate the Efficacy and Safety of Donepezil Transdermal Patch in Patients With Alzheimer’s Disease

• Han HJ
• Park MY
• Park KW
• Park KH
• Choi SH
• Kim HJ
• Yang DW
• Ebenezer EGAM
• Yang YH
• Kewalram GM
• Han SH
• on Behalf the IPI-301 Study

• KMID: 2530857
• DOI: http://doi.org/10.3988/jcn.2022.18.4.428

Abstract

Background and Purpose
Oral administration of cholinesterase inhibitors is often associated with adverse gastrointestinal effects, and so developing an alternative administration route, such as transdermal, is urgently needed. The primary objective of this study was to determine the efficacy and safety of the IPI-301 donepezil transdermal patch compared with donepezil tablets (control) in mild-to-moderate probable Alzheimer’s disease (AD).
Methods
This prospective, randomized, double-blind, double-dummy, two-arm parallel, multicenter trial included 399 patients, among whom 303 completed the trial. For randomization, the patients were stratified based on previous treatment and donepezil dose; patients in each stratum were randomized to the test and control groups at a 1:1 ratio.
Results
The difference between the control group and the IPI-301 group, quantified as the Hodges–Lehmann estimate of location shift, was 0.00 (95% confidence interval: -1.00 to 1.33), with an upper limit of less than 2.02. The change in Alzheimer’s Disease Cooperative Study– Activities of Daily Living (ADCS-ADL) score differed significantly between the IPI-301 and control groups (p=0.02). However, the changes in the full-itemized ADCS-ADL scores at week 24 did not differ significantly between the two groups. There were no differences between the two groups regarding the scores for the Clinician Interview-Based Impression of Change (f0.9097), Mini-Mental State Examination (p=0.7018), Neuropsychiatric Inventory (p=0.7656), or Clinical Dementia Rating (p=0.9990). Adverse events, vital signs, and laboratory test results were comparable between the two groups.
Conclusions
IPI-301 was safe and efficacious in improving cognitive function in patients with mild-to-moderate AD.

Keyword

donepezil transdermal patch; Alzheimer’s disease; efficacy; safety; acetylcholinesterase inhibitor