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

• Sponsor: Eisai Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00543855
• Collaborator: (none)
• Enrollment: 167
• Locations: 43
• Arms: 4
• Duration (Months): 27
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.1

Study Details

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
• 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: Nov 1, 2007
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 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) [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) [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) [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) [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

Criteria

• Ages Eligible for Study: 50 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

	Site	City	State	Country	Postal Code
1		Nagoya	Aichi	Japan
2		Obu	Aichi	Japan
3		Toyokawa	Aichi	Japan
4		Kurume	Fukuoka	Japan
5		Omuta	Fukuoka	Japan
6		Maebashi	Gunma	Japan
7		Miyoshi	Hiroshima	Japan
8		Otake	Hiroshima	Japan
9		Himeji	Hyogo	Japan
10		Kobe	Hyogo	Japan
11		Tsukuba	Ibaraki	Japan
12		Kahoku	Ishikawa	Japan
13		Morioka	Iwate	Japan
14		Yokohama	Kanagawa	Japan
15		Nankoku	Kochi	Japan
16		Koshi	Kumamoto	Japan
17		Joyo	Kyoto	Japan
18		Sendai	Miyagi	Japan
19		Komoro	Nagano	Japan
20		Kashihara	Nara	Japan
21		Joetsu	Niigata	Japan
22		Sanjo	Niigata	Japan
23		Yufu	Oita	Japan
24		Sakai	Osaka	Japan
25		Suita	Osaka	Japan
26		Izumo	Shimane	Japan
27		Bunkyo-ku	Tokyo	Japan
28		Kodaira	Tokyo	Japan
29		Koto-ku	Tokyo	Japan
30		Ota-ku	Tokyo	Japan
31		Setagaya-ku	Tokyo	Japan
32		Shinjuku-ku	Tokyo	Japan
33		Ube	Yamaguchi	Japan
34		Akita		Japan
35		Chiba		Japan
36		Fukui		Japan
37		Fukuoka		Japan
38		Kochi		Japan
39		Kumamoto		Japan
40		Kyoto		Japan
41		Osaka		Japan
42		Saitama		Japan
43		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.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Eisai Co., Ltd.
• ClinicalTrials.gov Identifier: NCT00543855
• Other Study ID Numbers: E2020-J081-431
• First Posted: Oct 15, 2007
• Last Update Posted: Mar 8, 2013
• Last Verified: Mar 1, 2013

• Keywords provided by Eisai Co., Ltd.: Lewy Body Disease; Dementia; Clinical Trial; Phase II; E2020; donepezil hydrochloride
• Additional relevant MeSH terms: Dementia; Lewy Body Disease; Donepezil

Study Results

Participant Flow

Pre-assignment Detail	167 participants initiated the Observation period, 140 participants were enrolled in the treatment period, one participant did not receive treatment.

Arm/Group Title	3 mg Donepezil Hydrochloride	5 mg Donepezil Hydrochloride	10 mg Donepezil Hydrochloride	Placebo
Arm/Group Description	E2020 (Aricept) : 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.	E2020 (Aricept) : 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).	E2020 (Aricept) : 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).	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.
Period Title: Overall Study
STARTED	35	33	37	34
COMPLETED	31	31	31	30
NOT COMPLETED	4	2	6	4

Baseline Characteristics

Arm/Group Title	3 mg Donepezil Hydrochloride	5 mg Donepezil Hydrochloride	10 mg Donepezil Hydrochloride	Placebo	Total
Arm/Group Description	E2020 (Aricept) : 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.	E2020 (Aricept) : 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).	E2020 (Aricept) : 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).	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.	Total of all reporting groups
Overall Participants	35	33	37	34	139
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	79.6 (4.5)	77.9 (6.7)	78.4 (6.1)	78.7 (4.9)	78.7 (5.6)
Sex: Female, Male (Count of Participants)
Female	18 51.4%	16 48.5%	33 89.2%	23 67.6%	90 64.7%
Male	17 48.6%	17 51.5%	4 10.8%	11 32.4%	49 35.3%

Outcome Measures

1. Primary Outcome

Title	Cognitive Function: Change From Baseline in Mini-mental State Examination (MMSE) Total at Week 12 Last Observation Carried Forward (LOCF)
Description	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.
Time Frame	Baseline and every 4 weeks up to 12 weeks

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS) was defined as those participants who complied with the study protocol.

Arm/Group Title	3 mg Donepezil Hydrochloride	5 mg Donepezil Hydrochloride	10 mg Donepezil Hydrochloride	Placebo
Arm/Group Description	E2020 (Aricept) : 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.	E2020 (Aricept) : 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).	E2020 (Aricept) : 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).	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.
Measure Participants	33	31	33	30
Baseline	20.1 (4.2)	19.7 (4.4)	19.7 (4.5)	18.2 (4.8)
Change from Baseline (LOCF)	1.2 (3.8)	3.5 (3.2)	2.3 (3.2)	-0.6 (2.7)

2. Primary Outcome

Title	Psychiatric Symptoms: Change From Baseline in Neuropsychiatric Inventory (NPI) Total at Week 12 Last Observation Carried Forward (LOCF)
Description	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.
Time Frame	Baseline and every 4 weeks up to 12 weeks

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS) was defined as those participants who complied with the study protocol.

Arm/Group Title	3 mg Donepezil Hydrochloride	5 mg Donepezil Hydrochloride	10 mg Donepezil Hydrochloride	Placebo
Arm/Group Description	E2020 (Aricept) : 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.	E2020 (Aricept) : 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).	E2020 (Aricept) : 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).	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.
Measure Participants	33	31	33	30
Baseline	20.9 (13.1)	14.2 (8.4)	19.1 (11.8)	18.4 (8.9)
Change from Baseline (LOCF)	-4.3 (21.5)	-5.9 (6.5)	-10.2 (12.0)	-3.1 (10.9)

3. Primary Outcome

Title	Global Clinical Function: Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-plus) Total at Week 12 Last Observation Carried Forward (LOCF)
Description	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.
Time Frame	Baseline and week 12

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS) was defined as those participants who complied with the study protocol.

Arm/Group Title	3 mg Donepezil Hydrochloride	5 mg Donepezil Hydrochloride	10 mg Donepezil Hydrochloride	Placebo
Arm/Group Description	E2020 (Aricept) : 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.	E2020 (Aricept) : 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).	E2020 (Aricept) : 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).	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.
Measure Participants	33	31	33	30
Marked improvement	3.6 10.3%	17.9 54.2%	3.8 10.3%	0 0%
Moderate Improvement	17.9 51.1%	17.9 54.2%	11.5 31.1%	3.7 10.9%
Minimal Improvement	50.0 142.9%	35.7 108.2%	50.0 135.1%	29.6 87.1%
No Change	21.4 61.1%	14.3 43.3%	30.8 83.2%	18.5 54.4%
Minimal Worsening	3.6 10.3%	7.1 21.5%	3.8 10.3%	37.0 108.8%
Moderate Worsening	0 0%	7.1 21.5%	0 0%	11.1 32.6%
Marked Worsening	3.6 10.3%	0 0%	0 0%	0 0%

4. Primary Outcome

Title	Burden on Caregiver: Change From Baseline in J-ZBI (Japanese- Zarit Caregiver Burden Interview) Total at Week 12 Last Observation Carried Forward (LOCF)
Description	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.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

Per Protocol Set (PPS) was defined as those participants who complied with the study protocol.

Arm/Group Title	3 mg Donepezil Hydrochloride	5 mg Donepezil Hydrochloride	10 mg Donepezil Hydrochloride	Placebo
Arm/Group Description	E2020 (Aricept) : 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.	E2020 (Aricept) : 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).	E2020 (Aricept) : 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).	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.
Measure Participants	33	31	33	30
Baseline	28.3 (14.4)	23.2 (11.6)	26.9 (16.3)	22.3 (9.8)
Change from Baseline (LOCF)	-1.3 (11.1)	-0.6 (16.4)	-5.2 (13.8)	2.9 (9.1)

Adverse Events

Adverse Event Reporting Description	Safety Analysis Set (SAS) was defined as all participants who received at least one dose of study drug and had at least one post-baseline safety evaluation.
Arm/Group Title	3 mg Donepezil Hydrochloride		5 mg Donepezil Hydrochloride		10 mg Donepezil Hydrochloride		Placebo
Arm/Group Description	E2020 (Aricept) : 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.		E2020 (Aricept) : 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).		E2020 (Aricept) : 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).		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.
All Cause Mortality
	3 mg Donepezil Hydrochloride		5 mg Donepezil Hydrochloride		10 mg Donepezil Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	3 mg Donepezil Hydrochloride		5 mg Donepezil Hydrochloride		10 mg Donepezil Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/35 (5.7%)		2/33 (6.1%)		4/37 (10.8%)		2/34 (5.9%)
Gastrointestinal disorders
Inguinal Hernia	0/35 (0%)		1/33 (3%)		0/37 (0%)		0/34 (0%)
Infections and infestations
Pyelonephritis	0/35 (0%)		0/33 (0%)		1/37 (2.7%)		0/34 (0%)
Injury, poisoning and procedural complications
Femur Fracture	0/35 (0%)		0/33 (0%)		1/37 (2.7%)		0/34 (0%)
Pelvic Fracture	0/35 (0%)		0/33 (0%)		0/37 (0%)		1/34 (2.9%)
Musculoskeletal and connective tissue disorders
Back Pain	0/35 (0%)		0/33 (0%)		1/37 (2.7%)		0/34 (0%)
Nervous system disorders
Cerebral Infarction	1/35 (2.9%)		0/33 (0%)		0/37 (0%)		0/34 (0%)
Diabetic Neuropathy	0/35 (0%)		0/33 (0%)		0/37 (0%)		1/34 (2.9%)
Paraparesis	0/35 (0%)		1/33 (3%)		0/37 (0%)		0/34 (0%)
Subarachnoid Haemorrhage	1/35 (2.9%)		0/33 (0%)		0/37 (0%)		0/34 (0%)
Psychiatric disorders
Hallucination	1/35 (2.9%)		0/33 (0%)		1/37 (2.7%)		0/34 (0%)
Restlessness	0/35 (0%)		0/33 (0%)		0/37 (0%)		1/34 (2.9%)
Other (Not Including Serious) Adverse Events
	3 mg Donepezil Hydrochloride		5 mg Donepezil Hydrochloride		10 mg Donepezil Hydrochloride		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	24/35 (68.6%)		27/33 (81.8%)		32/37 (86.5%)		24/34 (70.6%)
Gastrointestinal disorders
Diarrhoea	0/35 (0%)		4/33 (12.1%)		3/37 (8.1%)		4/34 (11.8%)
Constipation	0/35 (0%)		3/33 (9.1%)		1/37 (2.7%)		1/34 (2.9%)
Dental Caries	1/35 (2.9%)		2/33 (6.1%)		0/37 (0%)		1/34 (2.9%)
Abdominal Discomfort	0/35 (0%)		2/33 (6.1%)		0/37 (0%)		1/34 (2.9%)
Nausea	0/35 (0%)		0/33 (0%)		2/37 (5.4%)		1/34 (2.9%)
General disorders
Malaise	0/35 (0%)		2/33 (6.1%)		0/37 (0%)		0/34 (0%)
Infections and infestations
Nasopharyngitis	3/35 (8.6%)		2/33 (6.1%)		4/37 (10.8%)		1/34 (2.9%)
Gastroenteritis	0/35 (0%)		0/33 (0%)		3/37 (8.1%)		0/34 (0%)
Injury, poisoning and procedural complications
Contusion	2/35 (5.7%)		2/33 (6.1%)		1/37 (2.7%)		1/34 (2.9%)
Fall	0/35 (0%)		1/33 (3%)		2/37 (5.4%)		0/34 (0%)
Investigations
Blood Creatine Phosphokinase Increased	5/35 (14.3%)		3/33 (9.1%)		5/37 (13.5%)		2/34 (5.9%)
Blood Pressure Increased	5/35 (14.3%)		2/33 (6.1%)		2/37 (5.4%)		1/34 (2.9%)
Blood Urine Present	0/35 (0%)		2/33 (6.1%)		4/37 (10.8%)		3/34 (8.8%)
Blood Triglycerides Increased	2/35 (5.7%)		1/33 (3%)		0/37 (0%)		3/34 (8.8%)
Glucose Urine Present	0/35 (0%)		1/33 (3%)		3/37 (8.1%)		1/34 (2.9%)
White Blood Cell Count Decreased	0/35 (0%)		0/33 (0%)		4/37 (10.8%)		1/34 (2.9%)
Blood Urea Increased	1/35 (2.9%)		0/33 (0%)		1/37 (2.7%)		2/34 (5.9%)
Blood Alkaline Phosphatase Increased	0/35 (0%)		0/33 (0%)		1/37 (2.7%)		3/34 (8.8%)
Electrocardiogram QT Prolonged	0/35 (0%)		1/33 (3%)		0/37 (0%)		2/34 (5.9%)
Protein Urine Present	0/35 (0%)		2/33 (6.1%)		0/37 (0%)		0/34 (0%)
Metabolism and nutrition disorders
Diabetes Mellitus	0/35 (0%)		2/33 (6.1%)		1/37 (2.7%)		0/34 (0%)
Decreased Appetite	1/35 (2.9%)		0/33 (0%)		2/37 (5.4%)		0/34 (0%)
Musculoskeletal and connective tissue disorders
Back Pain	2/35 (5.7%)		1/33 (3%)		2/37 (5.4%)		3/34 (8.8%)
Arthralgia	0/35 (0%)		0/33 (0%)		0/37 (0%)		2/34 (5.9%)
Nervous system disorders
Parkinsonism	1/35 (2.9%)		2/33 (6.1%)		1/37 (2.7%)		0/34 (0%)
Psychiatric disorders
Poriomania	2/35 (5.7%)		0/33 (0%)		0/37 (0%)		0/34 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.