A Double-blind Study of E2020 (Donepezil Hydrochloride) in Patients With Dementia With Lewy Bodies (DLB) (Study E2020-J081-431)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of E2020 in patients with Dementia with Lewy Bodies (DLB).

Official Title
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Double-blind Study of E2020 in Patients With Dementia With Lewy Bodies - Phase II

Conditions
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Dementia With Lewy Bodies (DLB)

Intervention / Treatment
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* Drug: 3 mg Donepezil hydrochloride
* Drug: 5 mg Donepezil hydrochloride
* Drug: 10 mg Donepezil hydrochloride
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Patients diagnosed as probable Dementia With Lewy Bodies (DLB) according to the diagnostic criteria for DLB. Participants having caregivers who submit written consent for cooperative involvement in this study, can routinely stay with participants 3 days a week (at least 4 hours a day), provide participants' information necessary for this study, assist treatment compliance, and escort participants on required visits to study institution. Exclusion criteria: Participants with past experience of donepezil (Aricept) therapy at the same study institution. Participants treated with donepezil in 3 months immediately before starting the observation period. Participants with a complication of serious neuropsychiatric disease(s) such as stroke, brain tumor, schizophrenia, epilepsia, normal pressure hydrocephalus, mental retardation, brain trauma with unconsciousness, and/or experience of brain surgery causing unsolved deficiency. Participants with severe complication of cardiovascular, hepatic, renal, hematological, or other diseases unable to secure the safety. Pregnant or lactating women, or women who are willing to become pregnant no later than 1 month after the scheduled study completion Participants with severe extrapyramidal disorders (Hoehn & Yahr staging score is ≥IV) Participants whose systolic blood pressure is <90 mmHg or pulse rate is <50 beats/min. Participants suspected to have a complication of vascular dementia based upon neurological findings.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3 mg Donepezil hydrochloride<br> | Drug: 3 mg Donepezil hydrochloride<br>* Observation Period: Two Donepezil hydrochloride placebo tablets once daily by mouth after breakfast for 2 weeks. Treatment Period: One 3 mg Donepezil hydrochloride tablet by mouth plus one Donepezil hydrochloride placebo tablet by mouth, once daily for 12 weeks (Day 1- Day 84) after breakfast.<br>* Other names: E2020;|
| Experimental: 5 mg Donepezil hydrochloride<br> | Drug: 5 mg Donepezil hydrochloride<br>* Observation Period: Two Donepezil hydrochloride placebo tablets once daily by mouth after breakfast for 2 weeks. Treatment Period: One 3 mg Donepezil hydrochloride tablet by mouth plus one Donepezil hydrochloride placebo tablet by mouth, once daily after breakfast for Day 1- Day 14 (2 weeks). Followed by one 5 mg Donepezil hydrochloride tablet by mouth plus one Donepezil hydrochloride placebo tablet by mouth, once daily after breakfast for Day 15- Day 84 (10 weeks).<br>* Other names: E2020;|
| Experimental: 10 mg Donepezil hydrochloride<br> | Drug: 10 mg Donepezil hydrochloride<br>* Observation Period: Two Donepezil hydrochloride placebo tablets once daily by mouth after breakfast for 2 weeks. Treatment Period: One 3 mg Donepezil hydrochloride tablet by mouth plus one Donepezil hydrochloride placebo tablet by mouth, once daily after breakfast for Day 1- Day 14 (2 weeks). Followed by one 5 mg Donepezil hydrochloride tablet by mouth plus one Donepezil hydrochloride placebo tablet by mouth, once daily after breakfast for Day 15- Day 42 (4 weeks). Followed by two 5 mg Donepezil hydrochloride tablets (10 mg) by mouth, once daily after breakfast for Day 43 - Day 84 (6 weeks).<br>* Other names: E2020;|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Observation Period: Two Donepezil hydrochloride placebo tablets once daily by mouth after breakfast for 2 weeks. Treatment Period: Two Donepezil hydrochloride Placebo tablets by mouth, once daily for 12 weeks (Day 1- Day 84) after breakfast.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive Function: Change From Baseline in Mini-mental State Examination (MMSE) Total at Week 12 Last Observation Carried Forward (LOCF) | MMSE measured general cognitive functioning: orientation, memory, attention, calculation, language, visuospatial functions. Total score derived from sub-scores; total ranged from 0 - 30, where a higher score indicated better cognitive state. Change: mean score at Week 12 LOCF minus mean score at baseline. Values at final evaluation were imputed using a Last Observation Carried Forward (LOCF) method. | Baseline and every 4 weeks up to 12 weeks | 
| Psychiatric Symptoms: Change From Baseline in Neuropsychiatric Inventory (NPI) Total at Week 12 Last Observation Carried Forward (LOCF) | NPI measured 10 different domains of psychiatric symptoms including delusion and hallucination. Each domain is scored for: present or absent, frequency, and severity. The score derived from sub-scores; total ranged from 0 to 120, higher score indicated worse neuropsychiatric outcomes. Change: mean score at Week 12 LOCF minus mean score at baseline. Values at final evaluation were imputed using a Last Observation Carried Forward (LOCF) method. | Baseline and every 4 weeks up to 12 weeks | 
| Global Clinical Function: Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus) Total at Week 12 Last Observation Carried Forward (LOCF) | CIBIC plus is a clinician's interview-based impression of change plus the caregiver's input. It is a seven-point categorical assessment scale for evaluating global clinical function, ranging from markedly improved to markedly worse. Percentage of participants in each category were reported. Values at final evaluation were imputed using a Last Observation Carried Forward (LOCF) method. | Baseline and week 12 | 
| Burden on Caregiver: Change From Baseline in J-ZBI (Japanese- Zarit Caregiver Burden Interview) Total at Week 12 Last Observation Carried Forward (LOCF) | J-ZBI is a Japanese version instrument to measure and assess the level of burden experienced by the principal caregivers of participants with dementia. ZBI contains 22 items, in which each statement is scored by the caregiver using a 5-point scale. Response options range from 0 (Never) to 4 (Nearly Always). Total score derived from sub-scores; total ranged from 0-88. Higher scores indicate greater burden. Change: mean score at Week 12 LOCF minus mean score at baseline. Values at final evaluation were imputed using a Last Observation Carried Forward (LOCF) method. | Baseline and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lewy Body Disease, Dementia, Clinical Trial, Phase II, E2020, donepezil hydrochloride