A Randomized Double-Blind Study to Assess the Skin Irritation and Sensitization Potential of Once-Weekly Donepezil Transdermal Delivery System
Marwan Sabbagh1, Philip Mathew2, Alan Blau3
1Barrow Neurological Institute, 2Novum Pharmaceutical Research Services, 3Corium, Inc.
Objective:
To assess the skin irritation and sensitization potential of once-weekly 5-mg/d donepezil transdermal delivery system (TDS).
Background:
Once-weekly donepezil TDS (Adlarity®) was approved in 2022 by the US FDA for the treatment of mild, moderate, and severe dementia of the Alzheimer’s type.
Design/Methods:
In this placebo (vehicle), TDS-controlled, randomized, double-blind phase 1 trial (NCT03397862), healthy volunteers aged ≥40 years were evaluated for skin irritation and sensitization potential. Participants were randomized to receive weekly applications of 5-mg/d donepezil TDS on one side of the back and placebo TDS on the opposite side, or vice-versa, with 3 consecutive weekly TDS applications to the same skin site. During a challenge phase, donepezil TDS and placebo TDS were applied to naïve skin sites on opposite sides of the back in a randomized manner for 48 hours. Skin irritation scoring was performed weekly after TDS removal.
Results:
Among the 256 participants who received ≥1 dose of any treatment, the mean (SD) age was 54.3 years (9.4 years). After 3 weekly assessments of TDS, the average of the mean combined irritation score was 0.55 of a possible maximum 7 for donepezil TDS, indicating none-to-minimal skin irritation, and 0.19 for placebo TDS, indicating no skin irritation (treatment difference, −34 [95% CI, −0.43, −0.25]). There was a slight numerical trend of better skin tolerability in participants aged ≥65 versus <65 years. Of 198 participants, 4 (2.0%) were considered potentially sensitized to donepezil TDS, and 0 were potentially sensitized to placebo TDS.
Conclusions:
Once-weekly 5-mg/d donepezil TDS demonstrated acceptable skin tolerability, with minimal skin irritation under conditions of use of 3 consecutive weekly patch applications to the same skin site and minimal sensitization potential, supporting its use as treatment for dementia of the Alzheimer type.