A Study of E2020 in Patients With Dementia With Lewy Bodies (DLB), Followed by a Long-term Extension Phase - Full Text View

Purpose

The purpose of this study is to confirm the efficacy of E2020 in patients with dementia with Lewy bodies (DLB).

Condition	Intervention	Phase
Dementia With Lewy Bodies (DLB)	Drug: Donepezil 5 mg Drug: Donepezil 10 mg Drug: Donepezil matched placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Participant, Care Provider, Investigator) Primary Purpose: Treatment
Official Title:	A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of E2020 in Patients With Dementia With Lewy Bodies (DLB), Followed by a Long-term Extension Phase

Resource links provided by NLM:

MedlinePlus related topics: Dementia Lewy Body Disease

Drug Information available for: Donepezil hydrochloride Donepezil

U.S. FDA Resources

Further study details as provided by Eisai Inc. ( Eisai Co., Ltd. ):

Primary Outcome Measures:

Change From Baseline in Mini-Mental State Examination (MMSE) Score [ Time Frame: Week 12 for Confirmatory Phase ]
The MMSE was used to measure cognitive impairment. The MMSE can evaluate overall cognitive function, and is widely used for the assessment of cognitive impairment in dementia patients. The questionnaire consists of 11 items, and each item aims to evaluate different cognitive domains such as orientation, memory, attention, and construction. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from baseline. Data are presented as change from baseline in mean MMSE +/- standard deviation.
Change From Baseline in Neuropsychiatric Inventory (NPI-2) Score [ Time Frame: Week 12 for Confirmatory Phase ]
The NPI was a questionnaire that quantified psychiatric symptoms and behavioral disorders in dementia. A total of 12 items (the original NPI-10 consisting of 10 behavioral domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor behavior, supplemented by 2 dementia with Lewy bodies (DLB)-relevant domains of sleep, and cognitive fluctuation [reported as cognitive fluctuation inventory]) were assessed. The score of each item was calculated as frequency (scale: 1=occasionally to 4=very frequently) x Severity (scale: 1=Mild to 3=Severe). The NPI-2 was calculated as the sum of the scores for hallucinations and cognitive fluctuation, to yield a possible total score of 0 to 24. Lower score=less severity. A negative change score from baseline indicated improvement. Data are presented as change from baseline in mean NPI-2 +/- standard deviation.


Enrollment:	142
Study Start Date:	February 2011
Study Completion Date:	April 2013
Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Placebo Comparator: Placebo - Confirmatory Phase Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase.	Drug: Donepezil matched placebo
Experimental: Donepezil 5 mg - Confirmatory Phase Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 10 weeks in the confirmatory phase.	Drug: Donepezil 5 mg Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg Other Name: E2020
Experimental: Donepezil 10 mg - Confirmatory Phase Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 4 weeks. Thereafter, the dose was increased to 10 mg for 6 weeks in the confirmatory phase.	Drug: Donepezil 10 mg Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg and then the dose was increased to 10 mg Other Name: E2020
Experimental: Placebo to Donepezil (5 +10 mg) - Extension Phase Participants previously receiving donepezil matched placebo up to Week 12 in the Confirmatory Phase, continued placebo until Week 16 (at the beginning of the Extension Phase). Participants received 3 mg of donepezil, and the dose was then increased to 5 mg at Week 18 and to 10 mg at Week 24. After Week 24, dose reduction to 5 mg was allowed if continuation at 10 mg caused any safety concerns.	Drug: Donepezil 10 mg Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg and then the dose was increased to 10 mg Other Name: E2020
Experimental: Donepezil (5 +10 mg) - Extension Phase Participants previously receiving donepezil (5 mg or 10 mg) up to Week 12 in the Confirmatory Phase, maintained allocated treatment and dosages until Week 24. In the 5 mg group of the Confirmatory Phase, the dose was increased to 10 mg at Week 24. After Week 24, dose reduction to 5 mg was allowed if continuation at 10 mg caused any safety concerns.	Drug: Donepezil 10 mg Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg and then the dose was increased to 10 mg Other Name: E2020

Detailed Description:

This 52-week study consisted of 16-week randomized placebo-controlled (RCT, including 12-week Confirmatory Phase) 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.

Eligibility


Ages Eligible for Study:	50 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria

Patients diagnosed as probable dementia with Lewy bodies (DLB) according to the consensus diagnostic criteria for DLB
Patients having caregivers throughout the study who submited written consent to cooperate with this study, who routinely stayed with patients 3 days or more a week (at least 4 hours a day), provided patients' information necessary for this study, assisted treatment compliance, and escorted the patients on required visits to study institution
Clinical Dementia Rating (CDR) score ≥ 0.5
Mini-Mental State Examination (MMSE) score of 10 to 26

Exclusion Criteria

Patients diagnosed with Parkinson's disease with dementia (PDD)
Patients who received anti-dementia drug therapy at the same institution
Patients who received anti-dementia drug therapy within 12 weeks before start of Screening
Patients with a complication of serious neuropsychiatric disease(s) such as stroke, brain tumor, schizophrenia, epilepsy, normal pressure hydrocephalus, mental retardation, brain trauma with unconsciousness, or a history of brain surgery causing unrecovered deficiency
Patients with severe extrapyramidal disorders (Hoehn and Hahr staging score ≥ IV)
Patients whose systolic blood pressure was less than 90 mmHg or pulse rate was less than 50 bpm at screening

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01278407

Show 56 Study Locations

Sponsors and Collaborators

Eisai Co., Ltd.

Investigators


Study Director:	Masaki Nakagawa	Neuroscience Clinical Development Section. JAC PCU

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Mori E, Ikeda M, Nagai R, Matsuo K, Nakagawa M, Kosaka K. Long-term donepezil use for dementia with Lewy bodies: results from an open-label extension of Phase III trial. Alzheimers Res Ther. 2015 Feb 3;7(1):5. doi: 10.1186/s13195-014-0081-2. eCollection 2015.

Ikeda M, Mori E, Matsuo K, Nakagawa M, Kosaka K. Donepezil for dementia with Lewy bodies: a randomized, placebo-controlled, confirmatory phase III trial. Alzheimers Res Ther. 2015 Feb 3;7(1):4. doi: 10.1186/s13195-014-0083-0. eCollection 2015.


Responsible Party:	Eisai Co., Ltd.
ClinicalTrials.gov Identifier:	NCT01278407 History of Changes
Other Study ID Numbers:	E2020-J081-341
Study First Received:	January 14, 2011
Results First Received:	October 27, 2015
Last Updated:	December 30, 2015

Keywords provided by Eisai Inc. ( Eisai Co., Ltd. ):


DLB Dementia with Lewy bodies Lewy Body Disease Dementia	E2020 Donepezil Aricept

Additional relevant MeSH terms:


Dementia Lewy Body Disease Brain Diseases Central Nervous System Diseases Nervous System Diseases Neurocognitive Disorders Mental Disorders Parkinsonian Disorders Basal Ganglia Diseases Movement Disorders	Neurodegenerative Diseases Donepezil Cholinesterase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Cholinergic Agents Neurotransmitter Agents Physiological Effects of Drugs Nootropic Agents

ClinicalTrials.gov processed this record on July 13, 2017