Alzheimer's Disease
Conditions
Keywords
Alzheimer's disease
Brief summary
This is a multi-center, open-label, single-arm, prospective, phase IV trial, evaluating safety and efficacy of donepezil hydrochloride in patients with moderate to severe Alzheimer's disease.
Detailed description
This study consisted of pre-treatment and treatment phase. Pre-treatment phase was approximately 4 weeks including the screening and baseline process. In treatment phase, about 190 subjects received Donepezil HCl 23 mg once daily for 24 weeks.
Interventions
DRUGDonepezil HCL
Donepezil HCl 23 mg once daily, just before bed, for 24 weeks
Sponsors
Eisai Korea Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female aged 45 to 90 years 2. Patients have eligible conditions of dementia diagnosis listed in DSM-IV 3. Diagnosed as a probable Alzheimer's Disease patient according to NINCDS-ADRDA criteria 4. At the timing of screening, MMSE less than or equal to 20 AND CDR greater than or equal to 2 OR GDS greater than or equal to 4 5. Patients, who have been taking stable donepezil 10 mg for 3 months or longer before the start of the study (screening visit), are evaluated as eligible to take donepezil 23 mg by investigator 6. Patients who have not received any other medications for AD such as AChE inhibitors at least for 3 months prior to the screening visit excluding donepezil hydrochloride (However, concomitant use of memantine is allowed if taken at stable dose that are less than or equal to the approved dose range for at least 3 months prior to screening) 7. Medicines for cerebral activation such as Gingko Biloba is allowed to be taken if the patient has received it as stable dose for 3 months prior to the screening visit
Exclusion criteria
1. Patients who have been participated in any other clinical trial 3 months prior to the screening visit 2. Patients who are having any severe psychiatric disorder or schizophrenia 3. Patients who are having a neurological disorder other than AD which affect the subject's cognition or ability to assess the cognition
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Summary of Adverse Events (AEs) | Baseline (Day 1) up to Week 24 | Safety of study drug was assessed by clinical laboratory assessments, vital signs, weight, 12-lead electrocardiogram (ECG), physical and neurological examination. Treatment-Emergent Adverse Events (TEAEs) were defined as any event not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Serious adverse events were defined as AEs that led to or were life-threatening, resulted in or prolonged hospitalization, caused important or long-lasting disability, caused congenital abnormality or malformation, or resulted in death. Adverse drug reactions were defined as any harmful or unintended reaction to study treatment and were considered possibly related or probably related to study drug. Specific AEs and SAEs due to changes in clinical laboratory assessments, vital signs, weight, ECG, and physical and neurological exam are listed in the safety section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Mini-Mental State Examination (MMSE) Score | Baseline, Week 12, and Week 24 (Final visit) | The MMSE was used to measure cognitive impairment. The MMSE can evaluate overall cognitive function, and is widely used for the assessment of cognitive impairment in dementia patients. The questionnaire consists of 11 items, and each item aims to evaluate different cognitive domains such as orientation, memory, attention, and construction. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from baseline. The mean change was analyzed by Wilcoxon's signed rank test. |
| Change From Baseline in the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Distress Total Scores | Baseline, Week 12, and Week 24 (Follow up visit) | The NPI-Q assessed twelve behavioral domains common in dementia including; hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep/night-time behavior change, and appetite/eating change. The questionnaire is given by the clinician to the patient's caregiver who was asked if the behavior described is present in the patient. If Yes, the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale (1 = mild, 2= moderate, and 3= severe) and the associated impact of the symptom manifestations on them (i.e. Caregiver Distress) using a 5-point scale (0 = not distressing at all, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = extreme or very severe). The total severity score represents the sum of individual scores and ranges from 0 to 36. The total distress score represents the sum of individual symptom scores and ranges from 0 to 60. |
Countries
South Korea
Participant flow
Pre-assignment details
Out of the 171 participants enrolled into the study, 1 was not treated resulting in 170 participants in the safety population.
Participants by arm
| Arm | Count |
|---|---|
| Donepezil Hydrochloride Donepezil hydrochloride (HCl) at 23 mg was administered once daily, just before bed, for 24 weeks. | 170 |
| Total | 170 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 37 |
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Other | 2 |
| Overall Study | Protocol Violation | 2 |
| Overall Study | Withdrawal by Subject | 15 |
Baseline characteristics
| Characteristic | Donepezil Hydrochloride |
|---|---|
| Age, Continuous | 74.82 Years STANDARD_DEVIATION 7.18 |
| Sex: Female, Male Female | 123 Participants |
| Sex: Female, Male Male | 47 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 109 / 170 |
| serious Total, serious adverse events | 12 / 170 |
Outcome results
Primary
Overall Summary of Adverse Events (AEs)
Safety of study drug was assessed by clinical laboratory assessments, vital signs, weight, 12-lead electrocardiogram (ECG), physical and neurological examination. Treatment-Emergent Adverse Events (TEAEs) were defined as any event not present prior to the initiation of study treatment or any event already present that worsens in either intensity or frequency following exposure to study treatment. Serious adverse events were defined as AEs that led to or were life-threatening, resulted in or prolonged hospitalization, caused important or long-lasting disability, caused congenital abnormality or malformation, or resulted in death. Adverse drug reactions were defined as any harmful or unintended reaction to study treatment and were considered possibly related or probably related to study drug. Specific AEs and SAEs due to changes in clinical laboratory assessments, vital signs, weight, ECG, and physical and neurological exam are listed in the safety section.
Time frame: Baseline (Day 1) up to Week 24
Population: Safety population included all participants who received at least one dose of study treatment and had at least one postbaseline safety assessment.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Donepezil Hydrochloride | Overall Summary of Adverse Events (AEs) | AEs | 67.65 Percentage of participants |
| Donepezil Hydrochloride | Overall Summary of Adverse Events (AEs) | ADRs | 47.06 Percentage of participants |
| Donepezil Hydrochloride | Overall Summary of Adverse Events (AEs) | SAEs | 7.06 Percentage of participants |
| Donepezil Hydrochloride | Overall Summary of Adverse Events (AEs) | Serious ADRs | 0.59 Percentage of participants |
Secondary
Change From Baseline in the Mini-Mental State Examination (MMSE) Score
The MMSE was used to measure cognitive impairment. The MMSE can evaluate overall cognitive function, and is widely used for the assessment of cognitive impairment in dementia patients. The questionnaire consists of 11 items, and each item aims to evaluate different cognitive domains such as orientation, memory, attention, and construction. The score ranged from 0 to 30, with a higher score indicating better function. A positive change score indicated improvement from baseline. The mean change was analyzed by Wilcoxon's signed rank test.
Time frame: Baseline, Week 12, and Week 24 (Final visit)
Population: Efficacy analysis population included all participants who took at least one dose of study drug and had at least one baseline and at least one post-baseline assessment of the efficacy parameter. Twenty participants had no efficacy variables collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil Hydrochloride | Change From Baseline in the Mini-Mental State Examination (MMSE) Score | Change W12 | -0.31 Scores on a scale | Standard Deviation 2.76 |
| Donepezil Hydrochloride | Change From Baseline in the Mini-Mental State Examination (MMSE) Score | Change W24 | -0.40 Scores on a scale | Standard Deviation 2.75 |
Secondary
Change From Baseline in the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Distress Total Scores
The NPI-Q assessed twelve behavioral domains common in dementia including; hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep/night-time behavior change, and appetite/eating change. The questionnaire is given by the clinician to the patient's caregiver who was asked if the behavior described is present in the patient. If Yes, the informant then rates both the Severity of the symptoms present within the last month on a 3-point scale (1 = mild, 2= moderate, and 3= severe) and the associated impact of the symptom manifestations on them (i.e. Caregiver Distress) using a 5-point scale (0 = not distressing at all, 1 = minimal, 2 = mild, 3 = moderate, 4 = severe, and 5 = extreme or very severe). The total severity score represents the sum of individual scores and ranges from 0 to 36. The total distress score represents the sum of individual symptom scores and ranges from 0 to 60.
Time frame: Baseline, Week 12, and Week 24 (Follow up visit)
Population: Efficacy analysis population included all participants who took at least one dose of study drug and had at least one baseline and at least one post-baseline assessment of the efficacy parameter. Twenty participants had no efficacy variables collected.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil Hydrochloride | Change From Baseline in the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Distress Total Scores | Change Week 12 (Severity) | 0.33 Scores on a scale | Standard Deviation 4.74 |
| Donepezil Hydrochloride | Change From Baseline in the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Distress Total Scores | Change Week 12 (Distress) | 0.19 Scores on a scale | Standard Deviation 6.83 |
| Donepezil Hydrochloride | Change From Baseline in the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Distress Total Scores | Change Week 24 (Distress) | 0.29 Scores on a scale | Standard Deviation 7.6 |
| Donepezil Hydrochloride | Change From Baseline in the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Distress Total Scores | Change Week 24 (Severity) | 0.09 Scores on a scale | Standard Deviation 5.67 |