Evaluation of Skin Adhesion and Local Skin Tolerability of Once-Weekly Donepezil Transdermal System: Results of a Phase 1 Trial in Healthy Volunteers

Abstract: Donepezil transdermal system (TDS; Adlarity®) is approved for dementia of the Alzheimer’s type. Reported here are skin-adhesion and skin-tolerability evaluations of donepezil TDS in an open-label, phase 1, bioequivalence trial (NCT04617782) enrolling healthy volunteers aged 18-55 years. All participants used once-weekly 5-mg/d donepezil TDS for 5 weeks in Period 1, then once-weekly 10-mg/d TDS or once-daily 10-mg oral donepezil for 5 weeks in Period 2; treatments were switched in Period 3. TDS adhesion was assessed every 12 hours, during the weekly wear periods. Skin tolerability was assessed 0.5, 24, 48, and 72 hours after TDS removal using the US FDA-recommended dermal response criteria. Of 568 TDSs (296 of 5-mg/d and 272 of 10-mg/d), 563 were included in adhesion analysis. The mean percentages (standard deviation) of TDS surface area remaining adhered during weeks 1-5 were 92.6% (10.9%) and 93.3% (8.8%) for 5-mg/d and 10-mg/d TDSs, respectively; ≥75% adhesion was observed for 245 (83.6%) 5-mg/d and 232 (85.9%) 10-mg/d TDSs during the wear periods. Probability of a TDS maintaining ≥75% adhesion was 0.8362 for 5-mg/d and 0.8593 for 10-mg/d TDSs, and ≥80% of the TDSs were ≥75% adhered throughout the wear period. Skin tolerability was similar for 5-mg/d and 10-mg/d TDSs (0.5-hour postremoval combined skin irritation score ≥3 in 51.7% and 54.5% of participants, respectively). No participant discontinued; no TDSs were removed because of skin irritation. Once-weekly 5-mg/d and 10-mg/d donepezil TDSs demonstrated acceptable skin adhesion and tolerability, supporting their use as treatment for dementia of the Alzheimer’s type.Short Description: The poster will present skin-adhesion and local skin-tolerability data for donepezil transdermal system (TDS) evaluated in an open-label, phase 1, bioequivalence trial. The primary end point of the trial was to evaluate bioequivalence of once-weekly 5-mg/d and 10-mg/d donepezil TDSs with once-daily 10-mg oral donepezil (results presented in a separate poster). Our results show a favorable skin-adhesion and skin-tolerability profile of donepezil TDSs, supporting their use in patients with Alzheimer’s disease.Name of Sponsoring Organization(s): Corium, Inc