Open-Label Extension Study of 23 mg Donepezil SR in Participants With Moderate to Severe Alzheimer's Disease
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of long-term administration of 23 milligram (mg) donepezil sustained release (SR) in participants with moderate to severe Alzheimer's disease. Participants who complete study E2020-G000-326 (NCT00478205) with no ongoing serious adverse events (SAEs) and no serious adverse drug reactions will be eligible to enter the open-label extension study.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: Donepezil
Donepezil SR 23 mg once daily orally.
Other Names:
|
| Experimental: 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 immediate release (IR) in the preceding double-blind study E2020-G000-326 (NCT00478205). |
Drug: Donepezil
Donepezil SR 23 mg once daily orally.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events (AEs) [From the enrollment of the study up to 30 days after last dose of the study drug (up to 2 years 3 months)]
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.
Secondary Outcome Measures
- Percentage of Participants With at Least 1 Treatment-Emergent Abnormal Laboratory Values (TEAVs): Hematology [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 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.
- Percentage of Participants With at Least 1 TEAVs for Selected Parameters: Clinical Chemistry [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.
- Change From Baseline in Severe Impairment Battery (SIB) Total Score [At Baseline, Month 3, Month 6, Month 9 and Month 12]
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.
- Change From Baseline in Mini-Mental State Examination (MMSE) Total Score [At Baseline, Month 3, Month 6, Month 9 and Month 12]
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.
- Change From Baseline in Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Severe Scale (ADCS-ADL) Total Score [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.
- Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score [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.
- Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Total Score [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).
- Change From Baseline in Screen for Caregiver Objective Burden (SCB) Total Score [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).
- Change From Baseline in Screen for Caregiver Subjective Burden (SCB) Total Score [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).
- Number of Participants With Treatment Outcome Scale (TOS) Score [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).
- Goal Attainment Scaling (GAtS) Score Total Score [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]).
Eligibility Criteria
Criteria
Inclusion Criteria for Participants:
-
Written informed consent from the participant (if possible) or from the participant's legal guardian or other representative at the time of the Baseline visit, prior to beginning any assessments or activities.
-
Completion of study E2020-G000-326 (NCT00478205) without ongoing SAEs or history of serious adverse drug reactions during study E2020-G000-326 (NCT00478205).
-
Participant must enroll in the present study within 3 days of completion of study E2020-G000-326 (NCT00478205).
-
Health: physically healthy and ambulatory or ambulatory-aided (that is, walker or cane); corrected vision and hearing sufficient for compliance with testing procedures.
-
Co-morbid medical conditions must be well-controlled as determined by the investigator.
-
Participants undergoing treatment with selective serotonin reuptake inhibitors (SSRIs) may be included, provided that doses are within the approved dose range as specified in the Physician's Desk Reference or local equivalent
-
Concomitant Medications: Participants undergoing treatment with the following medications may be enrolled in the study provided the following conditions are met: chronic daily benzodiazepine use if doses are stable within an approved dose range; bronchodilator medications for treatment of chronic obstructive pulmonary disease (COPD) as long as drug is administered via metered dose inhaler within approved dose range; memantine if taken at doses of 20 mg/day or less, provided that the dose is stable.
-
The participants must have a relative/caregiver who supervises the regular taking of the drug at the correct dose and is alert for possible side effects, unless the participant's legal guardian takes on this task.
Inclusion Criteria for Caregivers. Written informed consent will be obtained from the designated caregiver for participation in study assessments. The caregiver must be sufficiently familiar with the participant (as determined by the investigator) to provide accurate data. Specifically, the caregiver must have sufficient contact with the participant to provide accurate reports of the participant's functioning, must be able to observe for possible adverse events, and must be able to accompany the participant to all visits. It is preferable that the caregiver be the same as in study E2020-G000-326 (NCT00478205). If no replacement caregiver is available who meets the caregiver inclusion/exclusion criteria, the participant must be discontinued from the study.
Exclusion Criteria for Participants:
-
No caregiver available to meet the inclusion criteria for caregivers.
-
Participants with any active or clinically-significant conditions affecting absorption, distribution, or metabolism of the study medication (example, inflammatory bowel disease, gastric or duodenal ulcers, hepatic disease, or severe lactose intolerance).
-
Known plan for elective surgery during the study period that would require general anesthesia and administration of neuromuscular blocking agents, such as succinylcholine, to induce paralysis/muscle relaxation. Minor surgery, such as colonoscopy or cataract surgery, will be permitted as long as it does not require the use of these paralytic agents.
-
Participants who are unwilling or unable to fulfill the requirements of the study.
-
Use of any prohibited prior or concomitant medications.
-
Any condition that would make the participant, in the opinion of the investigator, unsuitable for the study.
-
Participant taking concomitant antidepressant medication known to have significant anticholinergic effects, such as tricyclic antidepressants prescribed at doses recommended for the treatment of major depression.
-
Participants who cannot swallow or who have difficulty swallowing whole tablets.
-
Participants taking any alternative medication such as vitamins and/or herbal products or alternative medical techniques such as acupuncture or acupressure specifically for the treatment of Alzheimer's disease.
Exclusion Criteria for Caregivers.
-
Caregivers who are unwilling or unable to give informed consent or otherwise to fulfill the requirements of the study.
-
Any condition that would make the caregiver, in the opinion of the investigator, unsuitable for the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Apex Research Institute | Santa Ana | California | United States | 92705 |
Sponsors and Collaborators
- Eisai Inc.
- Eisai Limited
Investigators
- Study Director: Jane Yardley, Ph.D, Eisai Limited
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E2020-G000-328
- 2006-004890-93
Study Results
Participant Flow
| Recruitment Details | 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. |
|---|---|
| Pre-assignment Detail | 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). |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Period Title: Overall Study | ||
| STARTED | 570 | 332 |
| COMPLETED | 423 | 210 |
| NOT COMPLETED | 147 | 122 |
Baseline Characteristics
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) | Total |
|---|---|---|---|
| Arm/Group Description | 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 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 of all reporting groups |
| Overall Participants | 570 | 332 | 902 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
74.1
(8.67)
|
74.5
(8.44)
|
74.3
(8.58)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
373
65.4%
|
202
60.8%
|
575
63.7%
|
| Male |
197
34.6%
|
130
39.2%
|
327
36.3%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| Black |
16
2.8%
|
7
2.1%
|
23
2.5%
|
| White |
429
75.3%
|
245
73.8%
|
674
74.7%
|
| Hispanic |
42
7.4%
|
18
5.4%
|
60
6.7%
|
| Asian/Pacific |
80
14%
|
60
18.1%
|
140
15.5%
|
| Other |
3
0.5%
|
2
0.6%
|
5
0.6%
|
Outcome Measures
| Title | Number of Participants With Adverse Events (AEs) |
|---|---|
| Description | 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. |
| Time Frame | From the enrollment of the study up to 30 days after last dose of the study drug (up to 2 years 3 months) |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 570 | 332 |
| Count of Participants [Participants] |
416
73%
|
259
78%
|
| Title | Percentage of Participants With at Least 1 Treatment-Emergent Abnormal Laboratory Values (TEAVs): Hematology |
|---|---|
| Description | 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. |
| Time Frame | From the first dose of study drug up to 2 years 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 546 | 311 |
| Number [percentage of participants] |
9.5
1.7%
|
10.9
3.3%
|
| Title | Percentage of Participants With at Least 1 TEAVs for Selected Parameters: Clinical Chemistry |
|---|---|
| Description | 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. |
| Time Frame | From the first dose of study drug up to 2 years 3 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 553 | 312 |
| Number [percentage of participants] |
14.3
2.5%
|
13.1
3.9%
|
| Title | Change From Baseline in Severe Impairment Battery (SIB) Total Score |
|---|---|
| Description | 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. |
| Time Frame | At Baseline, Month 3, Month 6, Month 9 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 546 | 311 |
| At Baseline |
78.4
(19.05)
|
77.2
(19.49)
|
| Change at Month 3 |
-1.7
(7.11)
|
-0.9
(6.55)
|
| Change at Month 6 |
-4.0
(9.52)
|
-2.8
(8.68)
|
| Change at Month 9 |
-5.5
(11.19)
|
-5.2
(9.71)
|
| Change at Month 12 |
-7.5
(12.99)
|
-6.7
(10.75)
|
| Title | Change From Baseline in Mini-Mental State Examination (MMSE) Total Score |
|---|---|
| Description | 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. |
| Time Frame | At Baseline, Month 3, Month 6, Month 9 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 549 | 314 |
| Baseline |
14.1
(5.81)
|
13.8
(6.02)
|
| Change at Month 3 |
-0.6
(2.27)
|
-0.5
(2.20)
|
| Change at Month 6 |
-1.3
(2.70)
|
-1.2
(2.53)
|
| Change at Month 9 |
-1.7
(2.95)
|
-1.7
(2.77)
|
| Change at Month 12 |
-2.3
(3.08)
|
-2.1
(3.04)
|
| Title | Change From Baseline in Modified Alzheimer's Disease Cooperative Study Activities of Daily Living Severe Scale (ADCS-ADL) Total Score |
|---|---|
| Description | 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. |
| Time Frame | At Baseline, Month 3, Month 6, Month 9 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 556 | 315 |
| Baseline |
34.3
(11.26)
|
34.3
(11.26)
|
| Change at Month 3 |
-1.6
(5.30)
|
-1.8
(5.27)
|
| Change at Month 6 |
-3.2
(6.13)
|
-3.7
(6.53)
|
| Change at Month 9 |
-4.6
(6.91)
|
-4.8
(7.46)
|
| Change at Month 12 |
-5.6
(7.62)
|
-6.8
(8.96)
|
| Title | Change From Baseline in Quality of Life-Alzheimer's Disease (Qol-AD) Total Score |
|---|---|
| Description | 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. |
| Time Frame | At Baseline, Month 6 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 527 | 301 |
| Caregiver; Baseline |
31.6
(6.37)
|
30.8
(6.62)
|
| Caregiver; Change at Month 6 |
-1.4
(5.17)
|
-1.4
(5.08)
|
| Caregiver; Change at Month 12 |
-1.8
(5.60)
|
-1.8
(5.28)
|
| Participant; Baseline |
35.2
(6.65)
|
34.5
(6.90)
|
| Participant; Change at Month 6 |
-0.2
(5.10)
|
-0.1
(4.95)
|
| Participant; Change at Month 12 |
-0.2
(5.02)
|
-0.2
(4.76)
|
| Title | Change From Baseline in European Quality of Life-5 Dimension (EQ-5D) Total Score |
|---|---|
| Description | 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). |
| Time Frame | At Baseline, Month 6 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 531 | 303 |
| Baseline |
0.76
(0.17)
|
0.77
(0.19)
|
| Change at Month 6 |
-0.04
(0.15)
|
-0.04
(0.18)
|
| Change at Month 12 |
-0.06
(0.18)
|
-0.06
(0.19)
|
| Title | Change From Baseline in Screen for Caregiver Objective Burden (SCB) Total Score |
|---|---|
| Description | 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). |
| Time Frame | At Baseline, Month 6 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 520 | 296 |
| Baseline |
9.8
(4.36)
|
9.8
(4.74)
|
| Change at Month 6 |
0.5
(3.76)
|
1.0
(3.64)
|
| Change at Month 12 |
1.2
(3.94)
|
1.5
(3.98)
|
| Title | Change From Baseline in Screen for Caregiver Subjective Burden (SCB) Total Score |
|---|---|
| Description | 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). |
| Time Frame | At Baseline, Month 6 and Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 520 | 296 |
| Baseline |
18.4
(10.98)
|
18.5
(12.14)
|
| Change at Month 6 |
1.7
(10.03)
|
3.0
(9.63)
|
| Change at Month 12 |
3.2
(10.30)
|
4.3
(10.64)
|
| Title | Number of Participants With Treatment Outcome Scale (TOS) Score |
|---|---|
| Description | 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). |
| Time Frame | At Months 6 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 530 | 302 |
| 1=Very much improved |
10
1.8%
|
7
2.1%
|
| 2=Moderately improved |
56
9.8%
|
29
8.7%
|
| 3=Minimally improved |
66
11.6%
|
40
12%
|
| 4=About the same |
149
26.1%
|
79
23.8%
|
| 5=Minimally worse |
130
22.8%
|
73
22%
|
| 6=Moderately worse |
96
16.8%
|
57
17.2%
|
| 7=Very much worse |
23
4%
|
17
5.1%
|
| 1=Very much improved |
12
2.1%
|
5
1.5%
|
| 2=Moderately improved |
37
6.5%
|
20
6%
|
| 3=Minimally improved |
67
11.8%
|
23
6.9%
|
| 4=About the same |
91
16%
|
52
15.7%
|
| 5=Minimally worse |
103
18.1%
|
42
12.7%
|
| 6=Moderately worse |
89
15.6%
|
54
16.3%
|
| 7=Very much worse |
41
7.2%
|
26
7.8%
|
| Title | Goal Attainment Scaling (GAtS) Score Total Score |
|---|---|
| Description | 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]). |
| Time Frame | At Months 6 and 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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. |
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) |
|---|---|---|
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). |
| Measure Participants | 510 | 295 |
| Caregivers; At Month 6 |
-2.6
(9.63)
|
-3.2
(9.97)
|
| Caregivers At Month 12 |
-5.1
(11.10)
|
-5.9
(10.61)
|
| Participants; At Month 6 |
2.2
(7.34)
|
-0.8
(8.26)
|
| Participants; At Month 12 |
2.4
(7.89)
|
-0.6
(9.57)
|
Adverse Events
| Time Frame | From the first dose of study drug up to 2 years 3 months | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) | ||
| Arm/Group Description | 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 once daily orally for 12 months to participants who received donepezil 10 mg IR in the preceding double-blind study E2020-G000-326 (NCT00478205). | ||
All Cause Mortality |
||||
| Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 14/570 (2.5%) | 5/332 (1.5%) | ||
Serious Adverse Events |
||||
| Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 80/570 (14%) | 56/332 (16.9%) | ||
| Blood and lymphatic system disorders | ||||
| Anemia | 1/570 (0.2%) | 0/332 (0%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 0/570 (0%) | 1/332 (0.3%) | ||
| Angina pectoris | 1/570 (0.2%) | 0/332 (0%) | ||
| Arrhythmia supraventricular | 0/570 (0%) | 1/332 (0.3%) | ||
| Atrial fibrillation | 0/570 (0%) | 2/332 (0.6%) | ||
| Bradycardia | 2/570 (0.4%) | 0/332 (0%) | ||
| Cardiac failure | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Myocardial infarction | 2/570 (0.4%) | 0/332 (0%) | ||
| Ventricular tachycardia | 1/570 (0.2%) | 0/332 (0%) | ||
| Cardio-rspiratory arrest | 1/570 (0.2%) | 0/332 (0%) | ||
| Congenital, familial and genetic disorders | ||||
| Encephalocele | 0/570 (0%) | 1/332 (0.3%) | ||
| Hydrocele | 1/570 (0.2%) | 0/332 (0%) | ||
| Meningocele | 0/570 (0%) | 1/332 (0.3%) | ||
| Gastrointestinal disorders | ||||
| Abdominal pain | 0/570 (0%) | 1/332 (0.3%) | ||
| Diarrhoea | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Duodenal ulcer perforation | 1/570 (0.2%) | 0/332 (0%) | ||
| Gastric ulcer | 0/570 (0%) | 1/332 (0.3%) | ||
| Gastrointestinal hemorrhage | 1/570 (0.2%) | 0/332 (0%) | ||
| Haematemesis | 0/570 (0%) | 2/332 (0.6%) | ||
| Haematochezia | 1/570 (0.2%) | 0/332 (0%) | ||
| Ileus paralytic | 1/570 (0.2%) | 0/332 (0%) | ||
| Oesophageal ulcer | 1/570 (0.2%) | 0/332 (0%) | ||
| Pancreatic mass | 1/570 (0.2%) | 0/332 (0%) | ||
| Upper gastrointestinal hemorrhage | 1/570 (0.2%) | 0/332 (0%) | ||
| Vomiting | 0/570 (0%) | 1/332 (0.3%) | ||
| General disorders | ||||
| Asthenia | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Chest pain | 1/570 (0.2%) | 0/332 (0%) | ||
| Death | 2/570 (0.4%) | 0/332 (0%) | ||
| Gait disturbance | 1/570 (0.2%) | 0/332 (0%) | ||
| Multi-organ failure | 0/570 (0%) | 1/332 (0.3%) | ||
| Non-cardiac chest pain | 1/570 (0.2%) | 0/332 (0%) | ||
| Sudden death | 0/570 (0%) | 1/332 (0.3%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis acute | 0/570 (0%) | 1/332 (0.3%) | ||
| Hepatic cirrhosis | 0/570 (0%) | 1/332 (0.3%) | ||
| Infections and infestations | ||||
| Abdominal abscess | 1/570 (0.2%) | 0/332 (0%) | ||
| Bronchitis | 0/570 (0%) | 1/332 (0.3%) | ||
| Cellulitis staphylococcal | 1/570 (0.2%) | 0/332 (0%) | ||
| Gastroenteritis | 2/570 (0.4%) | 0/332 (0%) | ||
| Liver abscess | 0/570 (0%) | 1/332 (0.3%) | ||
| Lobar pneumonia | 0/570 (0%) | 1/332 (0.3%) | ||
| Lower respiratory tract infection | 2/570 (0.4%) | 0/332 (0%) | ||
| Orchitis | 1/570 (0.2%) | 0/332 (0%) | ||
| Peritonillar abscess | 1/570 (0.2%) | 0/332 (0%) | ||
| pneumonia | 6/570 (1.1%) | 1/332 (0.3%) | ||
| Respiratory tract infection | 0/570 (0%) | 1/332 (0.3%) | ||
| Sepsis | 1/570 (0.2%) | 0/332 (0%) | ||
| Tuberculosis | 1/570 (0.2%) | 0/332 (0%) | ||
| Urinary tract infection | 8/570 (1.4%) | 3/332 (0.9%) | ||
| Injury, poisoning and procedural complications | ||||
| Concussion | 1/570 (0.2%) | 0/332 (0%) | ||
| Device lead damage | 1/570 (0.2%) | 0/332 (0%) | ||
| Dislocation of joint prosthesis | 0/570 (0%) | 1/332 (0.3%) | ||
| Fall | 7/570 (1.2%) | 2/332 (0.6%) | ||
| Femoral neck fracture | 3/570 (0.5%) | 0/332 (0%) | ||
| Femur fracture | 2/570 (0.4%) | 0/332 (0%) | ||
| Head injury | 1/570 (0.2%) | 0/332 (0%) | ||
| Hip fracture | 2/570 (0.4%) | 1/332 (0.3%) | ||
| Laceration | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Lumbar vertebral fracture | 1/570 (0.2%) | 0/332 (0%) | ||
| Radius fracture | 0/570 (0%) | 1/332 (0.3%) | ||
| Road traffic accident | 1/570 (0.2%) | 0/332 (0%) | ||
| Skin laceration | 1/570 (0.2%) | 0/332 (0%) | ||
| Subdural haematoma | 1/570 (0.2%) | 3/332 (0.9%) | ||
| Thoracic vertebral fracture | 1/570 (0.2%) | 0/332 (0%) | ||
| Upper limb fracture | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Subdural haemorrhage | 1/570 (0.2%) | 0/332 (0%) | ||
| Investigations | ||||
| Electrocardiogram QT prolonged | 1/570 (0.2%) | 0/332 (0%) | ||
| Lipase increased | 0/570 (0%) | 1/332 (0.3%) | ||
| Weight decreased | 1/570 (0.2%) | 0/332 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 0/570 (0%) | 1/332 (0.3%) | ||
| Dehydration | 2/570 (0.4%) | 3/332 (0.9%) | ||
| Gout | 0/570 (0%) | 1/332 (0.3%) | ||
| Hypokalaemia | 1/570 (0.2%) | 0/332 (0%) | ||
| Hyponatremia | 0/570 (0%) | 2/332 (0.6%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Muscle rigidity | 0/570 (0%) | 1/332 (0.3%) | ||
| Osteoarthritis | 1/570 (0.2%) | 0/332 (0%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Breast cancer | 1/570 (0.2%) | 0/332 (0%) | ||
| Lung carcinoma cell type unspecified stage IV | 1/570 (0.2%) | 0/332 (0%) | ||
| Lung neoplasm | 1/570 (0.2%) | 0/332 (0%) | ||
| Malignant melanoma | 0/570 (0%) | 1/332 (0.3%) | ||
| Metastases to liver | 1/570 (0.2%) | 0/332 (0%) | ||
| Metastases to spine | 0/570 (0%) | 1/332 (0.3%) | ||
| Metastasis | 1/570 (0.2%) | 0/332 (0%) | ||
| Prostate cancer | 0/570 (0%) | 2/332 (0.6%) | ||
| Prostate cancer stage II | 0/570 (0%) | 1/332 (0.3%) | ||
| Rectal cancer | 1/570 (0.2%) | 0/332 (0%) | ||
| Lung neoplasm malignant | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Nervous system disorders | ||||
| Bradykinesia | 0/570 (0%) | 1/332 (0.3%) | ||
| Cerebral atrophy | 1/570 (0.2%) | 0/332 (0%) | ||
| Cerebral hemorrhage | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Cerebral infarction | 0/570 (0%) | 1/332 (0.3%) | ||
| Cerebrospinal fistula | 0/570 (0%) | 1/332 (0.3%) | ||
| Cerebrovascular accident | 5/570 (0.9%) | 2/332 (0.6%) | ||
| Convulsion | 1/570 (0.2%) | 0/332 (0%) | ||
| Dementia Alzheimers type | 2/570 (0.4%) | 570 | 0/332 (0%) | 570 |
| Dizziness | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Encephalopathy | 1/570 (0.2%) | 0/332 (0%) | ||
| Epilepsy | 0/570 (0%) | 1/332 (0.3%) | ||
| Headache | 0/570 (0%) | 1/332 (0.3%) | ||
| Hemiparesis | 1/570 (0.2%) | 0/332 (0%) | ||
| Hemiplegia | 0/570 (0%) | 1/332 (0.3%) | ||
| Hydrocephalus | 1/570 (0.2%) | 0/332 (0%) | ||
| Ischemic cerebral infarction | 0/570 (0%) | 1/332 (0.3%) | ||
| Lacunar infarction | 0/570 (0%) | 1/332 (0.3%) | ||
| Presyncope | 1/570 (0.2%) | 0/332 (0%) | ||
| Sciatica | 1/570 (0.2%) | 0/332 (0%) | ||
| Status epilepticus | 0/570 (0%) | 1/332 (0.3%) | ||
| Syncope | 6/570 (1.1%) | 6/332 (1.8%) | ||
| Transient ischemic attack | 1/570 (0.2%) | 3/332 (0.9%) | ||
| Unresponsive to stimuli | 1/570 (0.2%) | 0/332 (0%) | ||
| Psychiatric disorders | ||||
| Aggression | 1/570 (0.2%) | 3/332 (0.9%) | ||
| Agitation | 0/570 (0%) | 2/332 (0.6%) | ||
| Anxiety | 0/570 (0%) | 1/332 (0.3%) | ||
| Hallucination | 0/570 (0%) | 1/332 (0.3%) | ||
| Insomnia | 0/570 (0%) | 3/332 (0.9%) | ||
| Mental status change | 0/570 (0%) | 4/332 (1.2%) | ||
| Poriomania | 1/570 (0.2%) | 0/332 (0%) | ||
| Psychotic disorder | 0/570 (0%) | 1/332 (0.3%) | ||
| Restlessness | 1/570 (0.2%) | 2/332 (0.6%) | ||
| Renal and urinary disorders | ||||
| Calculus bladder | 1/570 (0.2%) | 0/332 (0%) | ||
| Haematuria | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Nephrolithiasis | 1/570 (0.2%) | 0/332 (0%) | ||
| Neurogenic bladder | 0/570 (0%) | 1/332 (0.3%) | ||
| Renal failure | 1/570 (0.2%) | 0/332 (0%) | ||
| Urinary retention | 1/570 (0.2%) | 0/332 (0%) | ||
| Renal failure acute | 1/570 (0.2%) | 2/332 (0.6%) | ||
| Reproductive system and breast disorders | ||||
| Benign prostatic hyperplasia | 2/570 (0.4%) | 0/332 (0%) | ||
| Prostatomegaly | 1/570 (0.2%) | 0/332 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Choking | 1/570 (0.2%) | 0/332 (0%) | ||
| Chronic obstructive pulmonary disease | 1/570 (0.2%) | 1/332 (0.3%) | ||
| Dyspnea | 3/570 (0.5%) | 0/332 (0%) | ||
| Lung disorder | 1/570 (0.2%) | 0/332 (0%) | ||
| Pleural effusion | 1/570 (0.2%) | 0/332 (0%) | ||
| Pulmonary embolism | 0/570 (0%) | 2/332 (0.6%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 1/570 (0.2%) | 0/332 (0%) | ||
| Hypertension | 0/570 (0%) | 1/332 (0.3%) | ||
| Hypotension | 1/570 (0.2%) | 0/332 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Donepezil SR 23 mg (Donepezil SR 23 mg in Study NCT00478205) | Donepezil SR 23 mg (Donepezil IR 10 mg in Study NCT00478205) | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 415/570 (72.8%) | 259/332 (78%) | ||
| Blood and lymphatic system disorders | ||||
| Anaemia | 3/570 (0.5%) | 9/332 (2.7%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 20/570 (3.5%) | 19/332 (5.7%) | ||
| Insomnia | 18/570 (3.2%) | 15/332 (4.5%) | ||
| Vomiting | 9/570 (1.6%) | 15/332 (4.5%) | ||
| Constipation | 6/570 (1.1%) | 8/332 (2.4%) | ||
| Abdominal pain | 6/570 (1.1%) | 7/332 (2.1%) | ||
| General disorders | ||||
| Nausea | 12/570 (2.1%) | 20/332 (6%) | ||
| Irritability | 13/570 (2.3%) | 7/332 (2.1%) | ||
| Oedema peripheral | 15/570 (2.6%) | 5/332 (1.5%) | ||
| Asthenia | 6/570 (1.1%) | 12/332 (3.6%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 14/570 (2.5%) | 11/332 (3.3%) | ||
| Injury, poisoning and procedural complications | ||||
| Fall | 54/570 (9.5%) | 25/332 (7.5%) | ||
| Contusion | 9/570 (1.6%) | 7/332 (2.1%) | ||
| Investigations | ||||
| Weight decreased | 58/570 (10.2%) | 43/332 (13%) | ||
| Weight increased | 15/570 (2.6%) | 12/332 (3.6%) | ||
| Metabolism and nutrition disorders | ||||
| Anorexia | 11/570 (1.9%) | 11/332 (3.3%) | ||
| Hypercholesterolaemia | 10/570 (1.8%) | 7/332 (2.1%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Arthralgia | 7/570 (1.2%) | 8/332 (2.4%) | ||
| Nervous system disorders | ||||
| Syncope | 19/570 (3.3%) | 9/332 (2.7%) | ||
| Dizziness | 6/570 (1.1%) | 12/332 (3.6%) | ||
| Psychiatric disorders | ||||
| Agitation | 33/570 (5.8%) | 28/332 (8.4%) | ||
| Aggression | 29/570 (5.1%) | 23/332 (6.9%) | ||
| Depression | 15/570 (2.6%) | 12/332 (3.6%) | ||
| Anxiety | 12/570 (2.1%) | 2/332 (0.6%) | ||
| Renal and urinary disorders | ||||
| Urinary tract infection | 33/570 (5.8%) | 20/332 (6%) | ||
| Urinary incontinence | 12/570 (2.1%) | 11/332 (3.3%) | ||
| Haematuria | 7/570 (1.2%) | 7/332 (2.1%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 7/570 (1.2%) | 7/332 (2.1%) | ||
| Vascular disorders | ||||
| Hypertension | 18/570 (3.2%) | 10/332 (3%) | ||
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Eisai Medical Information |
|---|---|
| Organization | Eisai, Inc. |
| Phone | +1-888-274-2378 |
| esi_medinfo@eisai.com |
- E2020-G000-328
- 2006-004890-93