Alzheimer's Type Dementia
Conditions
Keywords
Alzheimer Disease, Dementia, Delirium, Amnestic, Cognitive Disorders, Donepezil, Brain Diseases, Central Nervous System Diseases, Nervous System Diseases, Tauopathies, Neurodegenerative Diseases, Mental Disorders, Cholinesterase Inhibitors, Enzy
Brief summary
The purpose of this study is to compare 23 mg donepezil sustained release (SR) to the currently marketed formulation of 10 mg donepezil immediate release (IR) in patients with severe Alzheimer's disease.
Interventions
DRUGE2020
Patients will take study medication orally, once daily, for 2 weeks according to a double-dummy design in the double blind phase: 23 mg donepezil sustained release (SR) concurrently with placebo identical in appearance to the 10 mg donepezil immediate release (IR) formulation
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnostic evidence of probable Alzheimer's disease (AD) consistent with the Diagnostic and Statistical Manual for Mental Disorders-version IV (DSM-IV) * Hachinski Ischemic Score * Functional Assessment Staging (FAST) scale greater than or equal to 6 at Screening. * Mini-Mental State Examination (MMSE) score of 1 to 12 at Screening * Subjects who are on a stable Aricept- dose of 10 mg immediate release (IR), taken as a single, daily dose for 3 months prior to the Screening Visit * Evidence consistent with Alzheimer's disease (AD) on any cranial image on magnetic resonance imaging (MRI) or computed tomography (CT) scan or etc. obtained within 24 months prior to the Screening Visit. Subjects who have any observations of dementia other than Alzheimer's type after the last image diagnosis should be reconfirmed. * Age 50 years * Written informed consent is to have been obtained from the subject (if possible) or from the subject's legal guardian or other representative
Exclusion criteria
* Subjects with dementia other than Alzheimer's type * Subjects with significant neurological or psychiatric disorders such as stroke, brain tumor, schizophrenia, epilepsy, normal pressure hydrocephalus, mental retardation, a history of head injury with loss of consciousness, or a history of brain surgery followed by persistent deficits * Subjects with allergy to donepezil hydrochloride or piperidine derivatives * Subjects with a cause of Alzheimer's disease (AD) which is supported by any laboratory tests such as Vitamin B12, folate levels, triiodothyronine, free triiodothyronine, thyroxine, thyroid stimulating hormone (TSH) or serologic test for syphilis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum Observed Plasma Concentration (Cmax) of E2020 on Visits 2 and 3 | Visit 2 [Day1] and Visit 3 [Day 15] |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 2 [Day1] and Visit 3 [Day 15] | All subjects were identified as Extensive Metabolizer \[EM\] or Intermediate Metabolizer \[IM\] predicted from their CYP2D6 phenotypes. Ultra-rapid Metabolizer (UM) and Poor Metabolizer (PM) were not identified in any subject. Since the analysis population i |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| E2020 SR 23 mg E2020 SR 23 mg 1 tablet + E2020 10 mg placebo tablet once daily in the morning for 2 weeks in the double-blind phase. E2020 SR 23 mg once daily in the morning for 52 weeks in the extension phase. | 22 |
| E2020 10 mg E2020 10 mg 1 tablet + E2020 SR 23 mg placebo tablet once daily in the morning for 2 weeks in the double-blind phase. E2020 SR 23 mg once daily in the morning for 52 weeks in the extension phase. | 23 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-blind | Adverse Event | 2 | 0 |
| Double-blind | Withdrawal by Subject | 1 | 0 |
| Extension | Adverse Event | 2 | 5 |
| Extension | Physician Decision | 1 | 0 |
| Extension | Prohibited concomitant medications | 0 | 1 |
| Extension | Withdrawal by Subject | 1 | 2 |
| Extension | Withdrawal of study drug 4 days in a row | 3 | 1 |
Baseline characteristics
| Characteristic | E2020 SR 23 mg | E2020 10 mg | Total |
|---|---|---|---|
| Age, Continuous | 79.3 Years STANDARD_DEVIATION 9.8 | 73.6 Years STANDARD_DEVIATION 10.8 | 76.4 Years STANDARD_DEVIATION 10.6 |
| Hachinski Score | 1.1 Scores on a Scale STANDARD_DEVIATION 1.3 | 0.7 Scores on a Scale STANDARD_DEVIATION 1.1 | 0.9 Scores on a Scale STANDARD_DEVIATION 1.2 |
| Sex: Female, Male Female | 16 Participants | 16 Participants | 32 Participants |
| Sex: Female, Male Male | 6 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 13 / 22 | 2 / 23 | 9 / 19 | 16 / 23 |
| serious Total, serious adverse events | 0 / 22 | 0 / 23 | 0 / 19 | 1 / 23 |
Outcome results
Primary
Maximum Observed Plasma Concentration (Cmax) of E2020 on Visits 2 and 3
Time frame: Visit 2 [Day1] and Visit 3 [Day 15]
Population: Pharmacokinetic Analysis Set: the group of subjects who had received at least one quantifiable E2020 concentration in plasma
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E2020 SR 23 mg | Maximum Observed Plasma Concentration (Cmax) of E2020 on Visits 2 and 3 | Visit 2 | 126.503 ng/mL | Standard Deviation 31.27 |
| E2020 SR 23 mg | Maximum Observed Plasma Concentration (Cmax) of E2020 on Visits 2 and 3 | Visit 3 | 127.335 ng/mL | Standard Deviation 40.654 |
| E2020 10 mg (EM) | Maximum Observed Plasma Concentration (Cmax) of E2020 on Visits 2 and 3 | Visit 2 | 97.006 ng/mL | Standard Deviation 32.934 |
| E2020 10 mg (EM) | Maximum Observed Plasma Concentration (Cmax) of E2020 on Visits 2 and 3 | Visit 3 | 66.081 ng/mL | Standard Deviation 24 |
Secondary
Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status
All subjects were identified as Extensive Metabolizer \[EM\] or Intermediate Metabolizer \[IM\] predicted from their CYP2D6 phenotypes. Ultra-rapid Metabolizer (UM) and Poor Metabolizer (PM) were not identified in any subject. Since the analysis population i
Time frame: Visit 2 [Day1] and Visit 3 [Day 15]
Population: Pharmacokinetic Analysis Set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| E2020 SR 23 mg | Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 2 EM [IR: n=16, SR: n=17] | 117.999 ng/mL | Standard Deviation 28.898 |
| E2020 SR 23 mg | Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 2 IM [IR: n=5, SR: n=4] | 161.363 ng/mL | Standard Deviation 18.761 |
| E2020 SR 23 mg | Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 3 EM [IR: n=16, SR: n=15] | 116.771 ng/mL | Standard Deviation 31.663 |
| E2020 SR 23 mg | Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 2 IM [IR: n=5, SR: n=3] | 182.953 ng/mL | Standard Deviation 48.422 |
| E2020 10 mg (EM) | Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 2 IM [IR: n=5, SR: n=3] | 79.802 ng/mL | Standard Deviation 24.984 |
| E2020 10 mg (EM) | Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 2 EM [IR: n=16, SR: n=17] | 98.117 ng/mL | Standard Deviation 32.323 |
| E2020 10 mg (EM) | Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 3 EM [IR: n=16, SR: n=15] | 63.896 ng/mL | Standard Deviation 20.662 |
| E2020 10 mg (EM) | Cmax of E2020 on Visits 2 and 3 According to Cytochrome P450 2D6 (CYP2D6) Phenotype Status | Visit 2 IM [IR: n=5, SR: n=4] | 104.294 ng/mL | Standard Deviation 23.962 |