A Randomized Double-blind Study to Assess the Skin Irritation and Sensitization Potential of a Once-weekly Donepezil Transdermal Delivery System in Healthy Volunteers.

ABSTRACT

BACKGROUND: A once-weekly donepezil transdermal delivery system (TDS; Adlarity; Corium, LLC) is indicated for the treatment of mild, moderate, and severe dementia of the Alzheimer type. METHODS: In this placebo-controlled, randomized, double-blind phase 1 trial, healthy volunteers aged 40 years or older were randomized to receive a placebo and donepezil TDS and were evaluated for the primary endpoints of skin irritation and sensitization potential. Skin irritation was scored. RESULTS: Two hundred fifty-six participants were randomized and received ≥1 dose of any treatment. After the first weekly TDS application, no skin irritation or minimal irritation was evident between donepezil and placebo TDSs. At the third weekly TDS application, for donepezil TDS, the average of the mean combined skin irritation score was 0.55 of a possible maximum of 7, indicating none to minimal skin irritation, and for placebo, the score was 0.19, indicating no skin irritation. Of 198 participants, 4 (2.0%) were considered potentially sensitized to donepezil TDS, and 0 were potentially sensitized to placebo TDS. CONCLUSION: Once-weekly 5-mg/d donepezil TDS demonstrated minimal skin irritation under conditions of use of 3 consecutive weekly patch applications to the same skin site and minimal sensitization potential.