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

Phase 3

Completed

• Conditions: Dementia With Lewy Bodies (DLB)
• Interventions: Drug: Donepezil 10 mg; Drug: Donepezil matched placebo; Drug: Donepezil 5 mg

• Registration Number: NCT01278407
• Lead Sponsor: Eisai Co., Ltd.

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.

Study Timeline

• Study First Submitted: 2011-01-14
• Study First Submitted QC: 2011-01-14
• Study First Posted: 2011-01-17
• Study Start: 2011-02
• Primary Completion: 2013-03
• Study Completion: 2013-04
• Results First Submitted: 2015-10-27
• Results First Submitted QC: 2015-10-27
• Results First Posted: 2015-11-30
• Status Verified: 2015-12
• Last Update Submitted: 2023-06-16
• Last Update Posted: 2023-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 142

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Donepezil (5 +10 mg) - Extension Phase	Donepezil 10 mg	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.
Placebo - Confirmatory Phase	Donepezil matched placebo	Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase.
Placebo to Donepezil (5 +10 mg) - Extension Phase	Donepezil 10 mg	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.
Donepezil 10 mg - Confirmatory Phase	Donepezil 10 mg	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.
Donepezil 5 mg - Confirmatory Phase	Donepezil 5 mg	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Mini-Mental State Examination (MMSE) Score	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	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.