Trial Outcomes & Findings for Open-Label Extension Study of 23 mg Donepezil SR in Participants With Moderate to Severe Alzheimer's Disease (NCT NCT00566501)

Last Updated: 2021-11-17

Results Overview

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product, a change in treatment, or discontinuation of study drug, recurrence of an intermittent medical condition not present pretreatment, an abnormal laboratory test result was considered an AE if the identified laboratory abnormality led to any type of intervention, withdrawal of study drug, or withholding of study drug, whether prescribed in the protocol or not. All AEs in Study 328 (NCT00566501) excluding treatment-emergent signs or symptoms continuing from Study 326 (NCT00478205) were reported.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

915 participants

Primary outcome timeframe

From the enrollment of the study up to 30 days after last dose of the study drug (up to 2 years 3 months)

Results posted on

2021-11-17

Participant Flow

Participants took part in the study at 179 centers in Asia, Europe, North America, Oceania, South Africa, and South America during 14 December 2007 to 01 April 2010. This study E2020-G000-328 (NCT00566501) was a 12-month, open-label extension of study E2020-G000-326 (NCT00478205). Participants who had received donepezil 10 milligram (mg) immediate release (IR) or donepezil 23 mg sustained release (SR) during Study E2020-G000-326 (NCT00478205) were eligible for enrollment into this study.

A total of 1084 participants completed the study E2020-G000-326 (NCT00478205), of which 915 participants were enrolled and signed informed consent form and out of them, 902 participants received treatment in this study E2020-G000-328 (NCT00566501).

Participant milestones

Participant milestones
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Overall Study STARTED	570	332
Overall Study COMPLETED	423	210
Overall Study NOT COMPLETED	147	122

Reasons for withdrawal

Reasons for withdrawal
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Overall Study Adverse Event	68	59
Overall Study Medication Non-compliance	5	0
Overall Study Protocol Violation	2	2
Overall Study Request of Investigator or Sponsor	6	7
Overall Study Withdrawal by Subject	33	30
Overall Study Lack of Efficacy	8	3
Overall Study Other	25	21

Baseline Characteristics

Open-Label Extension Study of 23 mg Donepezil SR in Participants With Moderate to Severe Alzheimer's Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=570 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=332 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Total n=902 Participants Total of all reporting groups
Age, Continuous	74.1 years STANDARD_DEVIATION 8.67 • n=5 Participants	74.5 years STANDARD_DEVIATION 8.44 • n=7 Participants	74.3 years STANDARD_DEVIATION 8.58 • n=5 Participants
Sex: Female, Male Female	373 Participants n=5 Participants	202 Participants n=7 Participants	575 Participants n=5 Participants
Sex: Female, Male Male	197 Participants n=5 Participants	130 Participants n=7 Participants	327 Participants n=5 Participants
Race/Ethnicity, Customized Black	16 Participants n=5 Participants	7 Participants n=7 Participants	23 Participants n=5 Participants
Race/Ethnicity, Customized White	429 Participants n=5 Participants	245 Participants n=7 Participants	674 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	42 Participants n=5 Participants	18 Participants n=7 Participants	60 Participants n=5 Participants
Race/Ethnicity, Customized Asian/Pacific	80 Participants n=5 Participants	60 Participants n=7 Participants	140 Participants n=5 Participants
Race/Ethnicity, Customized Other	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the enrollment of the study up to 30 days after last dose of the study drug (up to 2 years 3 months)

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=570 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=332 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Number of Participants With Adverse Events (AEs)	416 Participants	259 Participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to 2 years 3 months

Population: The safety population included all participants who received at least one dose of the study medication during the open-label treatment period and had at least one post-baseline safety assessment. Here 'N' (overall number analyzed) are the participants who were evaluable for the outcome measure.

A TEAV for a laboratory parameter was defined as a value that was clinically significantly outside (above or below) the normal range post-dose, but within the normal range prior to drug administration, or a value that represented a clinically significant exacerbation of an abnormality present prior to drug administration. Abnormal values for hematology parameters were: White Blood cells count: less than or equal to \[\<=\] 2,800/per millimeter (mm) or greater than or equal to \[\>=\] 16,000/mm; Neutrophils: \<=15 percent (%); Hemoglobin: Male (\<=11.5 gram per deciliter \[g/dL\]), Female (\<=9.5 g/dL); Hematocrit: Male (\<=37%), Female (\<=32%); Eosinophils: \>=10%; Platelet Count: \<=75,000/mm or \>=700,000/mm. Percentage of participants with at least 1 abnormal TEAV for hematology was reported.

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=546 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=311 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Percentage of Participants With at Least 1 Treatment-Emergent Abnormal Laboratory Values (TEAVs): Hematology	9.5 percentage of participants	10.9 percentage of participants

SECONDARY outcome

Timeframe: From the first dose of study drug up to 2 years 3 months

A TEAV for a laboratory parameter was defined as a value that was clinically significantly outside (above or below) the normal range postdose, but within the normal range prior to drug administration,or a value that represented a clinically significant exacerbation of an abnormality present prior to drug administration.Abnormal values for clinical chemistry parameters were:Sodium:Less than(\<)130 milliequivalents per litre (mEq/L) or greater than(\>)150 mEq/L;Potassium:\<3 mEq/L or \>5.5 mEq/L; Calcium: \<8.4 milligram per deciliter (mg/dL) or \>1.5 mg/dL;Albumin: 50% lower limit of normal (LLN); Alkaline Phosphatase:\>=3\*upper limit of normal (ULN);Aspartate aminotransferase (AST):\>=3\*ULN;Alanine aminotransferase(ALT):\>=3\*ULN;Total Bilirubin:\>=2.0 mg/dL;Chloride:\<90 mEq/L or \>115 mEq/L;Creatinine:\>=2.0 mg/dL;Creatine phosphokinase:\>=3\*ULN;Blood Urea Nitrogen (BUN):\>=30 mg/dL. Percentage of participants with at least 1 abnormal TEAV (selected parameters) for clinical chemistry was reported.

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=553 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=312 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Percentage of Participants With at Least 1 TEAVs for Selected Parameters: Clinical Chemistry	14.3 percentage of participants	13.1 percentage of participants

SECONDARY outcome

Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12

Population: The Intent-to-treat (ITT) population included all safety participants who have at least one post-baseline efficacy measurement. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable at specified timepoints for this outcome measure.

The SIB evaluated the severity of cognitive dysfunction in participants with more advanced dementia. Test questions measured attention, language, orientation, memory, praxis, visuospatial ability, construction, social skills, orienting head to name. Non-verbal responses were allowed, thus decreasing the need for language output. Forty questions were included with a total possible score range of 0-100. Lower scores indicated greater cognitive impairment.

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=546 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=311 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Change From Baseline in Severe Impairment Battery (SIB) Total Score At Baseline	78.4 score on a scale Standard Deviation 19.05	77.2 score on a scale Standard Deviation 19.49
Change From Baseline in Severe Impairment Battery (SIB) Total Score Change at Month 3	-1.7 score on a scale Standard Deviation 7.11	-0.9 score on a scale Standard Deviation 6.55
Change From Baseline in Severe Impairment Battery (SIB) Total Score Change at Month 6	-4.0 score on a scale Standard Deviation 9.52	-2.8 score on a scale Standard Deviation 8.68
Change From Baseline in Severe Impairment Battery (SIB) Total Score Change at Month 9	-5.5 score on a scale Standard Deviation 11.19	-5.2 score on a scale Standard Deviation 9.71
Change From Baseline in Severe Impairment Battery (SIB) Total Score Change at Month 12	-7.5 score on a scale Standard Deviation 12.99	-6.7 score on a scale Standard Deviation 10.75

SECONDARY outcome

Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12

Population: The ITT population included all safety participants who have at least one post-baseline efficacy measurement. Here 'N' (overall number of participants analyzed) included all participants who were evaluable for this outcome measure and 'n' (number analyzed) included all participants who were evaluable at specified timepoints for this outcome measure.

MMSE is a 30-point scale that measured orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. Scores ranged from 0 (most impaired) to 30 (no impairment). Lower score indicated more impairment.

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=549 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=314 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Change From Baseline in Mini-Mental State Examination (MMSE) Total Score Baseline	14.1 score on a scale Standard Deviation 5.81	13.8 score on a scale Standard Deviation 6.02
Change From Baseline in Mini-Mental State Examination (MMSE) Total Score Change at Month 3	-0.6 score on a scale Standard Deviation 2.27	-0.5 score on a scale Standard Deviation 2.20
Change From Baseline in Mini-Mental State Examination (MMSE) Total Score Change at Month 6	-1.3 score on a scale Standard Deviation 2.70	-1.2 score on a scale Standard Deviation 2.53
Change From Baseline in Mini-Mental State Examination (MMSE) Total Score Change at Month 9	-1.7 score on a scale Standard Deviation 2.95	-1.7 score on a scale Standard Deviation 2.77
Change From Baseline in Mini-Mental State Examination (MMSE) Total Score Change at Month 12	-2.3 score on a scale Standard Deviation 3.08	-2.1 score on a scale Standard Deviation 3.04

SECONDARY outcome

Timeframe: At Baseline, Month 3, Month 6, Month 9 and Month 12

ADCS-ADL is a comprehensive battery of ADL questions used to measure a participant's functional capabilities. The modified ADCS-ADL-severe scale is a 19-item scale that has been validated for the assessment of participants with moderate to severe dementia. It measured the most appropriate basic and instrumental abilities (such as walking, grooming, bathing, and eating) in this participant population. Response to each item was obtained by interview with the caregiver. Ratings reflected caregiver observations about the participant's actual functioning and provided an assessment of change in the functional state of the participant over time. The total score ranged from 0 to 54. Lower scores indicated greater functional impairment.

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=556 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=315 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Change From Baseline in Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Severe Scale (ADCS-ADL) Total Score Baseline	34.3 score on a scale Standard Deviation 11.26	34.3 score on a scale Standard Deviation 11.26
Change From Baseline in Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Severe Scale (ADCS-ADL) Total Score Change at Month 3	-1.6 score on a scale Standard Deviation 5.30	-1.8 score on a scale Standard Deviation 5.27
Change From Baseline in Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Severe Scale (ADCS-ADL) Total Score Change at Month 6	-3.2 score on a scale Standard Deviation 6.13	-3.7 score on a scale Standard Deviation 6.53
Change From Baseline in Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Severe Scale (ADCS-ADL) Total Score Change at Month 9	-4.6 score on a scale Standard Deviation 6.91	-4.8 score on a scale Standard Deviation 7.46
Change From Baseline in Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Severe Scale (ADCS-ADL) Total Score Change at Month 12	-5.6 score on a scale Standard Deviation 7.62	-6.8 score on a scale Standard Deviation 8.96

SECONDARY outcome

Timeframe: At Baseline, Month 6 and Month 12

QoL-AD is a 13-item quality of life instrument developed to specifically assess QoL in participants who have dementia. Each item was scored on a 4-point scale (poor, fair, good, excellent) and a single score was calculated, ranging from 13 (low functioning) to 52 (normal function). Higher score indicated better QoL. The QoL-AD total scores for the participants and caregiver were the sum of the 13 items on each test.

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=527 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=301 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score Caregiver; Baseline	31.6 score on a scale Standard Deviation 6.37	30.8 score on a scale Standard Deviation 6.62
Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score Caregiver; Change at Month 6	-1.4 score on a scale Standard Deviation 5.17	-1.4 score on a scale Standard Deviation 5.08
Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score Caregiver; Change at Month 12	-1.8 score on a scale Standard Deviation 5.60	-1.8 score on a scale Standard Deviation 5.28
Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score Participant; Baseline	35.2 score on a scale Standard Deviation 6.65	34.5 score on a scale Standard Deviation 6.90
Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score Participant; Change at Month 6	-0.2 score on a scale Standard Deviation 5.10	-0.1 score on a scale Standard Deviation 4.95
Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score Participant; Change at Month 12	-0.2 score on a scale Standard Deviation 5.02	-0.2 score on a scale Standard Deviation 4.76

SECONDARY outcome

Timeframe: At Baseline, Month 6 and Month 12

EQ-5D is a health profile questionnaire assessing quality of life along 5 domains. Caregivers rated 5 domains of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The EQ-5D Health Utilities Index (HUI) is derived from the five dimensions of the EQ-5D, using country-specific preference weights (tariffs) to summarize how good or bad each health state is on a scale from 1 to 0. HSI total score ranged from 1 (full health) and 0 (worst health/death).

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=531 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=303 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Total Score Baseline	0.76 score on a scale Standard Deviation 0.17	0.77 score on a scale Standard Deviation 0.19
Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Total Score Change at Month 6	-0.04 score on a scale Standard Deviation 0.15	-0.04 score on a scale Standard Deviation 0.18
Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Total Score Change at Month 12	-0.06 score on a scale Standard Deviation 0.18	-0.06 score on a scale Standard Deviation 0.19

SECONDARY outcome

Timeframe: At Baseline, Month 6 and Month 12

The SCB is a 25-item instrument that questions caregivers about the occurrence and degree of distress as aspects of the burden of care during the preceding two weeks. It was designed specifically for use with caregivers of Alzheimer's disease participants. Each item was assessed on a 5-point scale ranging from "0" (no occurrence) to "4" (occurrence with severe distress). The objective burden was the sum of the total numbers of (1 2 3 4) in all items. Total score ranged from 0 (low distress) to 100 (high distress).

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=520 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=296 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Change From Baseline in Screen for Caregiver Objective Burden (SCB) Total Score Baseline	9.8 score on a scale Standard Deviation 4.36	9.8 score on a scale Standard Deviation 4.74
Change From Baseline in Screen for Caregiver Objective Burden (SCB) Total Score Change at Month 6	0.5 score on a scale Standard Deviation 3.76	1.0 score on a scale Standard Deviation 3.64
Change From Baseline in Screen for Caregiver Objective Burden (SCB) Total Score Change at Month 12	1.2 score on a scale Standard Deviation 3.94	1.5 score on a scale Standard Deviation 3.98

SECONDARY outcome

Timeframe: At Baseline, Month 6 and Month 12

The SCB is a 25-item instrument that questioned caregivers about the occurrence and degree of distress as aspects of the burden of care during the preceding two weeks. It was designed specifically for use with caregivers of Alzheimer's disease participants. Each item was assessed on a 5-point scale ranging from "0" (no occurrence) to "4" (occurrence with severe distress). The subjective burden was the sum of the (total number with score\*score). Total score ranged from 0 (no occurrence) to 100 (occurrence with severe distress).

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=520 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=296 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Change From Baseline in Screen for Caregiver Subjective Burden (SCB) Total Score Baseline	18.4 score on a scale Standard Deviation 10.98	18.5 score on a scale Standard Deviation 12.14
Change From Baseline in Screen for Caregiver Subjective Burden (SCB) Total Score Change at Month 6	1.7 score on a scale Standard Deviation 10.03	3.0 score on a scale Standard Deviation 9.63
Change From Baseline in Screen for Caregiver Subjective Burden (SCB) Total Score Change at Month 12	3.2 score on a scale Standard Deviation 10.30	4.3 score on a scale Standard Deviation 10.64

SECONDARY outcome

Timeframe: At Months 6 and 12

TOS is a pilot instrument designed to evaluate the caregiver's assessment of the participant's status. The caregiver was asked how much he/she thinks the participant has been helped by participating in the study. This instrument comprised a 7-point Likert scale in which a rating of 1=Very much improved; 2=Moderately improved; 3=Minimally improved; 4=About the same; 5=Minimally worse; 6=Moderately worse; 7=Very much worse. The total scale ranged from 1 (marked improvement) to 7 (marked worsening).

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=530 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=302 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 6 · 1=Very much improved	10 Participants	7 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 6 · 2=Moderately improved	56 Participants	29 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 6 · 3=Minimally improved	66 Participants	40 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 6 · 4=About the same	149 Participants	79 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 6 · 5=Minimally worse	130 Participants	73 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 6 · 6=Moderately worse	96 Participants	57 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 6 · 7=Very much worse	23 Participants	17 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 12 · 1=Very much improved	12 Participants	5 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 12 · 2=Moderately improved	37 Participants	20 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 12 · 3=Minimally improved	67 Participants	23 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 12 · 4=About the same	91 Participants	52 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 12 · 5=Minimally worse	103 Participants	42 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 12 · 6=Moderately worse	89 Participants	54 Participants
Number of Participants With Treatment Outcome Scale (TOS) Score At Month 12 · 7=Very much worse	41 Participants	26 Participants

SECONDARY outcome

Timeframe: At Months 6 and 12

GAtS is a technique that is standardized with respect to the general approach, but individualized with respect to the outcome goals of each participant. GAtS was designed to provide insight into the changes that are considered as important by the caregiver and (if feasible) by the participants. At study initiation, the participants (if capable) and, separately, the caregiver were asked to specify up to 4 goals for the participants during study participation. For each goal, a description of the current state (or one supplied with the help of the clinician if necessary) was provided to anchor the baseline assessment at 0, and other possible outcomes were described. The outcome for each goal was quantified by a 4-point scale that provided for improvement (+1, +2), no change (0) or worsening (-1, -2). Total score ranged from -30 (worsened) to 130 (most improved). Baseline score was set to be 50 (when scores of all goals are '0' \[no change\]).

Outcome measures

Outcome measures
Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=510 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=295 Participants Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Goal Attainment Scaling (GAtS) Score Total Score Caregivers; At Month 6	-2.6 score on a scale Standard Deviation 9.63	-3.2 score on a scale Standard Deviation 9.97
Goal Attainment Scaling (GAtS) Score Total Score Caregivers At Month 12	-5.1 score on a scale Standard Deviation 11.10	-5.9 score on a scale Standard Deviation 10.61
Goal Attainment Scaling (GAtS) Score Total Score Participants; At Month 6	2.2 score on a scale Standard Deviation 7.34	-0.8 score on a scale Standard Deviation 8.26
Goal Attainment Scaling (GAtS) Score Total Score Participants; At Month 12	2.4 score on a scale Standard Deviation 7.89	-0.6 score on a scale Standard Deviation 9.57

Adverse Events

Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205)

Serious events: 80 serious events

Other events: 415 other events

Deaths: 14 deaths

Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205)

Serious events: 56 serious events

Other events: 259 other events

Deaths: 5 deaths

Serious adverse events

Other adverse events

Additional Information

Eisai Medical Information

Eisai, Inc.

Phone: +1-888-274-2378

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) n=570 participants at risk Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 23 mg SR in the preceding double-blind study E2020-G000-326 (NCT00478205).	Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) n=332 participants at risk Donepezil SR 23 mg once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205).
Investigations Weight decreased	10.2% 58/570 • From the first dose of study drug up to 2 years 3 months	13.0% 43/332 • From the first dose of study drug up to 2 years 3 months
Injury, poisoning and procedural complications Fall	9.5% 54/570 • From the first dose of study drug up to 2 years 3 months	7.5% 25/332 • From the first dose of study drug up to 2 years 3 months
Psychiatric disorders Agitation	5.8% 33/570 • From the first dose of study drug up to 2 years 3 months	8.4% 28/332 • From the first dose of study drug up to 2 years 3 months
Renal and urinary disorders Urinary tract infection	5.8% 33/570 • From the first dose of study drug up to 2 years 3 months	6.0% 20/332 • From the first dose of study drug up to 2 years 3 months
Gastrointestinal disorders Diarrhoea	3.5% 20/570 • From the first dose of study drug up to 2 years 3 months	5.7% 19/332 • From the first dose of study drug up to 2 years 3 months
Psychiatric disorders Aggression	5.1% 29/570 • From the first dose of study drug up to 2 years 3 months	6.9% 23/332 • From the first dose of study drug up to 2 years 3 months
General disorders Nausea	2.1% 12/570 • From the first dose of study drug up to 2 years 3 months	6.0% 20/332 • From the first dose of study drug up to 2 years 3 months
Gastrointestinal disorders Insomnia	3.2% 18/570 • From the first dose of study drug up to 2 years 3 months	4.5% 15/332 • From the first dose of study drug up to 2 years 3 months
Vascular disorders Hypertension	3.2% 18/570 • From the first dose of study drug up to 2 years 3 months	3.0% 10/332 • From the first dose of study drug up to 2 years 3 months
Nervous system disorders Syncope	3.3% 19/570 • From the first dose of study drug up to 2 years 3 months	2.7% 9/332 • From the first dose of study drug up to 2 years 3 months
Psychiatric disorders Depression	2.6% 15/570 • From the first dose of study drug up to 2 years 3 months	3.6% 12/332 • From the first dose of study drug up to 2 years 3 months
Investigations Weight increased	2.6% 15/570 • From the first dose of study drug up to 2 years 3 months	3.6% 12/332 • From the first dose of study drug up to 2 years 3 months
Infections and infestations Nasopharyngitis	2.5% 14/570 • From the first dose of study drug up to 2 years 3 months	3.3% 11/332 • From the first dose of study drug up to 2 years 3 months
Gastrointestinal disorders Vomiting	1.6% 9/570 • From the first dose of study drug up to 2 years 3 months	4.5% 15/332 • From the first dose of study drug up to 2 years 3 months
Renal and urinary disorders Urinary incontinence	2.1% 12/570 • From the first dose of study drug up to 2 years 3 months	3.3% 11/332 • From the first dose of study drug up to 2 years 3 months
Metabolism and nutrition disorders Anorexia	1.9% 11/570 • From the first dose of study drug up to 2 years 3 months	3.3% 11/332 • From the first dose of study drug up to 2 years 3 months
General disorders Irritability	2.3% 13/570 • From the first dose of study drug up to 2 years 3 months	2.1% 7/332 • From the first dose of study drug up to 2 years 3 months
General disorders Oedema peripheral	2.6% 15/570 • From the first dose of study drug up to 2 years 3 months	1.5% 5/332 • From the first dose of study drug up to 2 years 3 months
General disorders Asthenia	1.1% 6/570 • From the first dose of study drug up to 2 years 3 months	3.6% 12/332 • From the first dose of study drug up to 2 years 3 months
Nervous system disorders Dizziness	1.1% 6/570 • From the first dose of study drug up to 2 years 3 months	3.6% 12/332 • From the first dose of study drug up to 2 years 3 months
Metabolism and nutrition disorders Hypercholesterolaemia	1.8% 10/570 • From the first dose of study drug up to 2 years 3 months	2.1% 7/332 • From the first dose of study drug up to 2 years 3 months
Injury, poisoning and procedural complications Contusion	1.6% 9/570 • From the first dose of study drug up to 2 years 3 months	2.1% 7/332 • From the first dose of study drug up to 2 years 3 months
Musculoskeletal and connective tissue disorders Arthralgia	1.2% 7/570 • From the first dose of study drug up to 2 years 3 months	2.4% 8/332 • From the first dose of study drug up to 2 years 3 months
Psychiatric disorders Anxiety	2.1% 12/570 • From the first dose of study drug up to 2 years 3 months	0.60% 2/332 • From the first dose of study drug up to 2 years 3 months
Gastrointestinal disorders Constipation	1.1% 6/570 • From the first dose of study drug up to 2 years 3 months	2.4% 8/332 • From the first dose of study drug up to 2 years 3 months
Respiratory, thoracic and mediastinal disorders Cough	1.2% 7/570 • From the first dose of study drug up to 2 years 3 months	2.1% 7/332 • From the first dose of study drug up to 2 years 3 months
Blood and lymphatic system disorders Anaemia	0.53% 3/570 • From the first dose of study drug up to 2 years 3 months	2.7% 9/332 • From the first dose of study drug up to 2 years 3 months
Gastrointestinal disorders Abdominal pain	1.1% 6/570 • From the first dose of study drug up to 2 years 3 months	2.1% 7/332 • From the first dose of study drug up to 2 years 3 months
Renal and urinary disorders Haematuria	1.2% 7/570 • From the first dose of study drug up to 2 years 3 months	2.1% 7/332 • From the first dose of study drug up to 2 years 3 months