Why this study mattered
Donepezil is a first-line treatment for Alzheimer’s-type dementia and has been prescribed for decades as a once-daily tablet. A patch version, Donhesive 175 mg/50 cm², could suit patients who find daily swallowing or remembering doses difficult.
But moving from tablet to patch changes more than the packaging. How the drug is absorbed, how often it is dosed and how the product sits on the skin all become evidence a regulator needs to see. The sponsor needed proof that the patch delivers donepezil at the same steady-state level as the tablet. Steady state is the point where the amount of drug in the body has levelled out after repeated dosing.
The primary goal: show comparative bioavailability between the Donhesive patch (twice weekly for 4 weeks, after a 1-week premedication with an 87.5 mg/25 cm² patch) and the Aricept® 10 mg tablet (once daily for 4 weeks, after a 7-day premedication with a 5 mg tablet).
The secondary goals: monitor safety and tolerability for both regimens, and describe the patch through steady-state pharmacokinetics and adhesion performance, following FDA guidance.
Each volunteer took part in a crossover design: they received both products, one after the other, in a randomly assigned order. Each period began with its own premedication phase so that volunteers started the main treatment already at steady state.
What made this study different
Two treatments, two periods, two sequences, each with its own premedication phase.
Twice-weekly patches against once-daily tablets, for four consecutive weeks each. The tablet was taken under fasting conditions.
Every 24 hours (±60 minutes) on the 5-point FDA scale, with an estimated percent adherence and photos at every timepoint.
Application site examined before dosing and every 24 hours after, using an 8-point irritation scale. Every reaction went through the adverse-event process.
Leftover donepezil measured in each used patch and on the skin beneath it, then compared with the original patch content.
Volunteers seen every 7 days (±2 days) after the first dose for a scheduled safety review.
Four challenges, and how we solved them
Comparing a slow-release patch with a daily tablet fairly
A patch releases the drug continuously, while a tablet is absorbed in one go. The two had to be compared on equal footing, without steady state on one arm hiding or exaggerating differences from the other.
- A multiple-dose, steady-state protocol for both arms.
- A dedicated premedication phase in every period.
- PK sampling started only once each treatment reached a stable, comparable baseline.
Keeping volunteers engaged for two four-week periods
Four weeks of treatment per period, repeated across two periods, is a long commitment. Retention and dosing compliance were real risks.
- Ambulatory safety visits every 7±2 days throughout each treatment phase.
- Regular checkpoints to confirm compliance and address concerns early.
- Volunteers kept engaged through both crossover periods.
Scoring patch adhesion and skin irritation consistently
Adhesion and irritation scores depend on the observer. With assessments every 24 hours across weeks of continuous wear, there was plenty of room for inconsistency.
- Every evaluator standardized on the FDA 5-point adhesion scale and 8-point irritation scale.
- Assessment windows fixed at ±60 minutes.
- A percent-adherence estimate and photos required at each timepoint, so scoring stays consistent and auditable.
Measuring how much drug the patch actually delivers
Unlike a tablet, a patch’s delivered dose is not fixed at manufacture. It depends on how much drug is left behind when the patch comes off, so it had to be measured.
- Every patch retrieved immediately after PK sampling.
- Residual donepezil quantified in the patch and on the skin underneath.
- Percutaneous absorption calculated against the drug content of an original, unused patch.
What the study delivered
- A completed steady-state comparative bioavailability dataset for the Donhesive patch and the Aricept® tablet, from a design built to make the two routes comparable.
- A full adhesion record for the treatment period, scored on the FDA scale and backed by percent-adherence estimates and photos at every 24-hour timepoint.
- A structured skin-tolerability record for the whole wear period, with every reaction captured and managed through standard adverse-event procedures.
- A quantified percutaneous absorption result for the patch, based on measured residual drug. This is a key input to the sponsor’s regulatory submission.
- A safety and tolerability profile for both multiple-dose regimens, monitored through scheduled ambulatory visits across the four-week treatment phase of each period.