Results of a double-blind phase 2b study of monthly mimopezil implants compared to oral donepezil in patients with moderate Alzheimer's disease (BRAINZ study)

Mimopezil is a huperzine A derivative with a potent and selective acetylcholinesterase inhibition action. In a previous phase IIa study, daily administration of oral mimopezil delayed cognitive decline in patients with mild to moderate AD and was specifically associated with a high responder rate on MMSE. A sustained-release mimopezil formulation (implants for s.c. injection) has been developed to overcome the poor compliance often associated with oral treatments in AD patients. Single or repeated administration of these implants to healthy volunteers at doses of 3 to 15 mg monthly resulted in a prolonged release of huperzine A for up to four weeks. The purpose of the current report is to provide the efficacy and safety results of a phase IIb study of the mimopezil implants in AD patients. Patients were randomised according to a double-blind, double-dummy design to receive either mimopezil or donepezil treatment for 6 months. Patients in the mimopezil arm received 1 mg mimopezil daily orally during the 1-month titration period, 9 mg mimopezil as s.c. implants in the 1-month maintenance I period, and 12 mg mimopezil as s.c. implants in the 4-month maintenance II period. Patients in the donepezil group received oral donepezil 5 mg daily during the titration period and 10 mg during both maintenance periods. Patients underwent regular assessments during the study. Efficacy will be reported on the following endpoints: change in MMSE score from baseline, MMSE responder rate, change on ADAS-Cog, NPI-Q, IADL scales. Safety will be reported on standard parameters. A total of 158 patients were enrolled in 27 sites over 3 continents. The study is ongoing and so far, above 800 implantations procedures have been performed and well tolerated. Sixteen SAEs have been reported, most of them not related to study drug. Due to the double-blind design, efficacy/safety results are not available at the time of submission of this abstract. A double-blind study of mimopezil implants is ongoing in AD patients. Unblinded efficacy and safety results will be disclosed during the conference.