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

• ClinicalTrials.gov Identifier: NCT00543855
• Recruitment Status: Completed
• First Posted: October 15, 2007
• Results First Posted: February 18, 2013
• Last Update Posted: March 8, 2013
• Sponsor: Eisai Co., Ltd.
• Information provided by (Responsible Party): Eisai Inc. ( Eisai Co., Ltd. )

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Dementia With Lewy Bodies (DLB)	Drug: 3 mg Donepezil hydrochloride; Drug: 5 mg Donepezil hydrochloride; Drug: 10 mg Donepezil hydrochloride; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 167 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Double-blind Study of E2020 in Patients With Dementia With Lewy Bodies - Phase II
• Study Start Date: November 2007
• Actual Primary Completion Date: February 2010
• Actual Study Completion Date: February 2010

Arms and Interventions

Arm	Intervention/treatment
Experimental: 3 mg Donepezil hydrochloride	Drug: 3 mg Donepezil hydrochloride; 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.; Other Names: Aricept; Donepezil hydrochloride; E2020
Experimental: 5 mg Donepezil hydrochloride	Drug: 5 mg Donepezil hydrochloride; 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).; Other Names: Aricept; Donepezil hydrochloride; E2020
Experimental: 10 mg Donepezil hydrochloride	Drug: 10 mg Donepezil hydrochloride; 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).; Other Names: Aricept; Donepezil hydrochloride; E2020
Placebo Comparator: Placebo	Drug: Placebo; 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.

Outcome Measures

Primary Outcome Measures :

1. Cognitive Function: Change From Baseline in Mini-mental State Examination (MMSE) Total at Week 12 Last Observation Carried Forward (LOCF) [ Time Frame: Baseline and every 4 weeks up to 12 weeks ]
   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.
2. Psychiatric Symptoms: Change From Baseline in Neuropsychiatric Inventory (NPI) Total at Week 12 Last Observation Carried Forward (LOCF) [ Time Frame: Baseline and every 4 weeks up to 12 weeks ]
   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.
3. Global Clinical Function: Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus) Total at Week 12 Last Observation Carried Forward (LOCF) [ Time Frame: Baseline and week 12 ]
   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.
4. Burden on Caregiver: Change From Baseline in J-ZBI (Japanese- Zarit Caregiver Burden Interview) Total at Week 12 Last Observation Carried Forward (LOCF) [ Time Frame: Baseline and Week 12 ]

   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.

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Locations

Japan

Nagoya, Aichi, Japan

Obu, Aichi, Japan

Toyokawa, Aichi, Japan

Kurume, Fukuoka, Japan

Omuta, Fukuoka, Japan

Maebashi, Gunma, Japan

Miyoshi, Hiroshima, Japan

Otake, Hiroshima, Japan

Himeji, Hyogo, Japan

Kobe, Hyogo, Japan

Tsukuba, Ibaraki, Japan

Kahoku, Ishikawa, Japan

Morioka, Iwate, Japan

Yokohama, Kanagawa, Japan

Nankoku, Kochi, Japan

Koshi, Kumamoto, Japan

Joyo, Kyoto, Japan

Sendai, Miyagi, Japan

Komoro, Nagano, Japan

Kashihara, Nara, Japan

Joetsu, Niigata, Japan

Sanjo, Niigata, Japan

Yufu, Oita, Japan

Sakai, Osaka, Japan

Suita, Osaka, Japan

Izumo, Shimane, Japan

Bunkyo-ku, Tokyo, Japan

Kodaira, Tokyo, Japan

Koto-ku, Tokyo, Japan

Ota-ku, Tokyo, Japan

Setagaya-ku, Tokyo, Japan

Shinjuku-ku, Tokyo, Japan

Ube, Yamaguchi, Japan

Akita, Japan

Chiba, Japan

Fukui, Japan

Fukuoka, Japan

Kochi, Japan

Kumamoto, Japan

Kyoto, Japan

Osaka, Japan

Saitama, Japan

Shizuoka, Japan

Sponsors and Collaborators

Eisai Co., Ltd.

Investigators

• Study Director: Masaki Nakagawa; Neurosciences Clinical Development Section, Japan / Asia Clinical Research, Product Creation Unit, Eisai Product Creation System.

More Information

• Responsible Party: Eisai Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00543855
• Other Study ID Numbers: E2020-J081-431
• First Posted: October 15, 2007
• Results First Posted: February 18, 2013
• Last Update Posted: March 8, 2013
• Last Verified: March 2013

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

Lewy Body Disease; Dementia; Clinical Trial; Phase II; E2020; donepezil hydrochloride

Additional relevant MeSH terms:

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