PMID- 25713599
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150225
LR  - 20220310
IS  - 1758-9193 (Print)
IS  - 1758-9193 (Electronic)
VI  - 7
IP  - 1
DP  - 2015
TI  - Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled, 
      confirmatory phase III trial.
PG  - 4
LID - 10.1186/s13195-014-0083-0 [doi]
LID - 4
AB  - INTRODUCTION: The efficacy of a cholinesterase inhibitor, donepezil, in patients 
      with dementia with Lewy bodies (DLB) was investigated to confirm the superiority 
      over placebo in the 12-week, double-blind phase of this phase III study. METHODS: 
      Patients with probable DLB (n = 142) were randomly assigned to placebo or to 5 mg 
      or 10 mg of donepezil administered once daily for 12 weeks. The co-primary 
      endpoints were changes in cognitive function assessed using the Mini-Mental State 
      Examination (MMSE) and behavioral and neuropsychiatric symptoms using the 
      Neuropsychiatric Inventory (NPI-2: hallucinations and fluctuations). The 
      superiority of each active group over placebo was determined with simultaneous 
      statistical significance in both endpoints. Safety evaluations included adverse 
      events (AEs) and the unified Parkinson's disease rating scale (UPDRS) part III. 
      RESULTS: The predefined superiority of donepezil to the placebo was not confirmed 
      in either active group in the primary analysis. MMSE score significantly improved 
      compared to placebo in the 10 mg group (10 mg: 2.2 +/- 0.4, placebo: 0.6 +/- 0.5 
      (mean +/- standard error); P = 0.016). The change in MMSE score in the 5 mg group 
      was not significant (1.4 +/- 0.5 (mean +/- standard error); P = 0.232). Although 
      NPI-2 improved compared to baseline in the active groups, the differences from 
      placebo were not significant. Most AEs were mild or moderate. Although the 
      incidence of parkinsonism was slightly higher in the 10 mg group, the change in 
      the UPDRS score was minimal and without a significant difference from the placebo 
      group. CONCLUSIONS: The co-primary endpoints were not achieved in this trial. 
      However, significant improvement in MMSE score was demonstrated with 10 mg, but 
      not 5 mg, of donepezil. The evaluation of psychiatric symptoms might be affected 
      by advanced education and instructions given to caregivers. Overall, donepezil 
      was well tolerated in patients with DLB. With careful attention on 
      gastrointestinal or parkinsonian symptoms, patients with DLB can safely benefit 
      from treatment with donepezil. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: 
      NCT01278407 (trial registration date: 14 January 2011).
FAU - Ikeda, Manabu
AU  - Ikeda M
AD  - Department of Neuropsychiatry, Faculty of Life Sciences, Kumamoto University, 
      1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556 Japan.
FAU - Mori, Etsuro
AU  - Mori E
AD  - Department of Behavioral Neurology and Cognitive Neuroscience, Tohoku University 
      Graduate School of Medicine, 2-1, Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575 
      Japan.
FAU - Matsuo, Kazutaka
AU  - Matsuo K
AD  - Eisai Product Creation Systems, Eisai Co. Ltd, 4-6-10 Koishikawa, Bunkyo-ku, 
      Tokyo 112-8088 Japan.
FAU - Nakagawa, Masaki
AU  - Nakagawa M
AD  - Eisai Product Creation Systems, Eisai Co. Ltd, 4-6-10 Koishikawa, Bunkyo-ku, 
      Tokyo 112-8088 Japan.
FAU - Kosaka, Kenji
AU  - Kosaka K
AD  - Department of Psychiatry, Yokohama City University School of Medicine, 3-9 
      Fukuura, Kanazawa-ku, Yokohama, Kanagawa 236-0004 Japan.
LA  - eng
SI  - ClinicalTrials.gov/NCT01278407
PT  - Journal Article
DEP - 20150203
PL  - England
TA  - Alzheimers Res Ther
JT  - Alzheimer's research & therapy
JID - 101511643
PMC - PMC4338565
EDAT- 2015/02/26 06:00
MHDA- 2015/02/26 06:01
PMCR- 2015/02/03
CRDT- 2015/02/26 06:00
PHST- 2014/04/28 00:00 [received]
PHST- 2014/11/12 00:00 [accepted]
PHST- 2015/02/26 06:00 [entrez]
PHST- 2015/02/26 06:00 [pubmed]
PHST- 2015/02/26 06:01 [medline]
PHST- 2015/02/03 00:00 [pmc-release]
AID - 83 [pii]
AID - 10.1186/s13195-014-0083-0 [doi]
PST - epublish
SO  - Alzheimers Res Ther. 2015 Feb 3;7(1):4. doi: 10.1186/s13195-014-0083-0. 
      eCollection 2015.