Transdermal Donepezil Provides Drug Delivery Equivalent to Oral Donezepil With Favorable GI Side Effect Profile
Results from a phase 1 trial (NCT04617782) show that both strengths of a donepezil transdermal system (Adlarity; Corium, Boston, MA) maintain equivalent daily exposure of donepezil compared to oral formulations of the drug and have a favorable gastrointestinal (GI) side effect profile.
The therapy is indicated for patients with mild, moderate, or severe dementia due to Alzheimer disease (AD) in 5 or 10 mg/day, once-weekly formulations.
Per guidance from the Food and Drug Administration (FDA), 2 pharmaceutical products are bioequivalent if the 90% confidence interval of the geometric mean ratio (GMR) for AUC and Cmax is within 80%-125%. The study concluded that the GMR for AUC and Cmax were within the bioequivalence range when comparing the 10 mg/day transdermal dose to 10 mg/day oral donepezil.
“The doses of the once-weekly donepezil transdermal system were equivalent to oral donepezil on a milligram-per-day basis, and the safety profile of the transdermal system formulation, including the lower overall incidence of GI side effects, support its use in treating patients with dementia of the Alzheimer’s type,” said Pierre N. Tariot, MD, director, Banner Alzheimer’s Institute.
In the study, fewer overall gastrointestinal adverse effects (AEs) occurred with administration of 10mg/day transdermal vs oral donepezil: 14.5% vs. 53.6%, respectively. The respective incidence rates were 5.5% vs. 17.9% for constipation, 1.8% vs. 30.4% for nausea, 3.6% vs. 12.5% for diarrhea, 5.5% vs. 1.8% for abdominal pain, and 0 vs. 5.4% for vomiting.
The trial included 3 treatment periods of 5 weeks each. In the first period, all 60 participants received 5 mg/day transdermal donepezil. In the second, participants were randomly assigned to receive either 10 mg/day once-weekly transdermal donepezil or 10 mg/day oral donepezil, followed by switching to the alternative treatment in the third period.
The study results were reported in a poster at the Alzheimer's Association International Conference 2022 (AAIC) in San Diego and online.