%0 Journal Article
%T Donepezil Plus Solifenacin (CPC-201) Treatment for Alzheimer¡¯s Disease
%A Kathleen Clarence-Smith
%A Martin R. Farlow
%A Thomas N. Chase
%J Archive of "Neurotherapeutics".
%D 2017
%R 10.1007/s13311-016-0511-x
%X Available cholinergic drugs for treating Alzheimer¡¯s disease (AD) provide modest symptomatic benefit. We hypothesized that co-administration of a peripheral anticholinergic to reduce dose-limiting adverse effects (AEs) would enable the safe/tolerable use of higher cholinesterase inhibitor doses and thus improve their antidementia efficacy. A modified single-blind, ascending-dose, phase IIa study of donepezil plus solifenacin (CPC-201) lasting 26 weeks was conducted in 41 patients with probable AD of moderate severity. Entry criteria included the use of donepezil at a dose of 10 mg/day during the preceding 3 months. The primary outcome measure was the maximum tolerated dose (MTD) of donepezil achieved (to protocol limit of 40 mg/day) when administered with the anticholinergic solifenacin 15 mg/day. Secondary measures included assessments of cognitive and global function, as well as of AEs. The mean£¿¡À£¿SD donepezil MTD increased to 38£¿¡À£¿0.74 mg/day (median 40 mg/day; p£¿<£¿0.001); 88% of the study population safely attained this dose at the end of titration. Markedly reduced donepezil AE frequency, especially gastrointestinal, allowed this dose increase. There were no drug-related serious AEs or clinically significant laboratory abnormalities. At 26 weeks, Alzheimer¡¯s Disease Assessment Scale Cognitive Component scores in the efficacy evaluable population improved by 0.35£¿¡À£¿0.85 points over baseline (p£¿<£¿0.05), an estimated 2.5£¿¡À£¿0.84 points above 10 mg/day donepezil and 5.4£¿¡À£¿0.84 points above historic placebo (both p£¿<£¿0.05). Clinical Global Impression of Improvement scores improved by 0.94£¿¡À£¿0.20 to 3.1£¿¡À£¿0.20 points (p£¿<£¿0.001). The findings suggest that limiting donepezil AEs by co-administration of solifenacin allows the safe administration of substantially higher cholinesterase inhibitors doses that may augment cognitive and global benefits in patients with AD
%K Dementia
%K clinical trial
%K donepezil
%K solifenacin
%K cholinesterase inhibitor
%K anticholinergic.
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5398986/