title: Long-term donepezil use for dementia with Lewy bodies: results from an open-label extension of Phase III trial.
abstract: BACKGROUND
  The long-term efficacy and safety of donepezil 10 mg in patients with dementia with Lewy bodies (DLB) were investigated in a 52-week Phase 3 trial.
  
  
  METHODS
  This 52-week study consisted of 16-week randomized placebo-controlled (RCT) and 36-week open-label extension phases. Of 142 DLB patients enrolled in the RCT phase (three arms: placebo, 5 mg, and 10 mg), 110 entered the extension phase. The placebo group of the RCT phase initiated active treatment at week 16, and the active groups maintained allocated treatment and dosages until week 24. After week 24, all patients received 10 mg. Dose reduction to 5 mg for safety concerns was allowed. Efficacy measures included Mini-Mental State Examination (MMSE) for cognitive function and Neuropsychiatric Inventory (NPI) for behavioral symptoms. Safety evaluations included adverse events (AEs) and the unified Parkinson disease rating scale.
  
  
  RESULTS
  In total, 100 subjects completed the study. Cognitive function improvement was sustained for 52 weeks (MMSE at week 52 in 10 mg: 2.8 ± 3.5 (mean ± standard deviation); P <0.001, Student paired t test)). Those who received placebo in the RCT phase showed an improvement after starting active treatment. NPI improved in all the groups throughout the study, including the placebo period. In the subgroup of the 5 mg group without remarkable cognitive or behavioral improvement at week 24, further improvement was observed after a dose increase to 10 mg. After week 24, 21 patients experienced dose reduction. The incidence of any AEs did not increase over time.
  
  
  CONCLUSIONS
  The long-term administration of donepezil at 10 mg/day improved cognitive function for up to 52 weeks in patients with DLB without increasing the risk of clinically significant safety events.
  
  
  BACKGROUND
  NCT01278407. Trial registration date: January 14, 2011.
authors.affiliation: Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 Japan.
authors.forename: Etsuro
authors.initials: E
authors.lastname: Mori
authors.affiliation: Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Ikeda
authors.affiliation: Eisai Product Creation Systems, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo 112-8088 Japan.
authors.forename: Reiko
authors.initials: R
authors.lastname: Nagai
authors.affiliation: Eisai Product Creation Systems, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo 112-8088 Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Eisai Product Creation Systems, Eisai Co., Ltd., 4-6-10 Koishikawa, Bunkyo-ku, Tokyo 112-8088 Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakagawa
authors.affiliation: Department of Psychiatry, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004 Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kosaka