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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to confirm the efficacy of E2020 in patients with dementia with Lewy bodies (DLB).

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.

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

Conditions
-----------------
Dementia With Lewy Bodies (DLB)

Intervention / Treatment
-----------------
* Drug: Donepezil 5 mg
* Drug: Donepezil 10 mg
* Drug: Donepezil matched placebo


Participation Criteria
=================
Eligibility 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

Ages Eligible for Study
-----------------
Minimum Age: 50 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo - Confirmatory Phase<br>Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase. | Drug: Donepezil matched placebo<br> <br> |
| Experimental: Donepezil 5 mg - Confirmatory Phase<br>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<br>* Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg<br>* Other names: E2020;|
| Experimental: Donepezil 10 mg - Confirmatory Phase<br>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<br>* Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg and then the dose was increased to 10 mg<br>* Other names: E2020;|
| Experimental: Placebo to Donepezil (5 +10 mg) - Extension Phase<br>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<br>* Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg and then the dose was increased to 10 mg<br>* Other names: E2020;|
| Experimental: Donepezil (5 +10 mg) - Extension Phase<br>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<br>* Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg and then the dose was increased to 10 mg<br>* Other names: E2020;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Mini-Mental State Examination (MMSE) Score | 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. | Week 12 for Confirmatory Phase | 
| Change From Baseline in Neuropsychiatric Inventory (NPI-2) Score | 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. | Week 12 for Confirmatory Phase | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
DLB, Dementia with Lewy bodies, Lewy Body Disease, Dementia, E2020, Donepezil, Aricept