Dementia With Lewy Bodies (DLB)
Conditions
Keywords
DLB, Dementia with Lewy bodies, Lewy Body Disease, Dementia, E2020, Donepezil, Aricept
Brief summary
The purpose of this study is to confirm the efficacy of E2020 in patients with dementia with Lewy bodies (DLB).
Detailed description
This 52-week study consisted of 16-week randomized placebo-controlled (RCT, including 12-week Confirmatory Phase) and 36-week open-label extension phases. Of 142 DLB patients enrolled in the RCT phase (three arms: placebo, 5 mg, and 10 mg), 110 entered the extension phase. The placebo group of the RCT phase initiated active treatment at week 16, and the active groups maintained allocated treatment and dosages until week 24. After week 24, all patients received 10 mg. Dose reduction to 5 mg for safety concerns was allowed.
Interventions
DRUGDonepezil 5 mg
Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg
DRUGDonepezil 10 mg
Donepezil tablets orally, once daily, uptitrated from 3 to 5 mg and then the dose was increased to 10 mg
DRUGDonepezil matched placebo
Sponsors
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients diagnosed as probable dementia with Lewy bodies (DLB) according to the consensus diagnostic criteria for DLB 2. Patients having caregivers throughout the study who submited written consent to cooperate with this study, who routinely stayed with patients 3 days or more a week (at least 4 hours a day), provided patients' information necessary for this study, assisted treatment compliance, and escorted the patients on required visits to study institution 3. Clinical Dementia Rating (CDR) score ≥ 0.5 4. Mini-Mental State Examination (MMSE) score of 10 to 26
Exclusion criteria
1. Patients diagnosed with Parkinson's disease with dementia (PDD) 2. Patients who received anti-dementia drug therapy at the same institution 3. Patients who received anti-dementia drug therapy within 12 weeks before start of Screening 4. Patients with a complication of serious neuropsychiatric disease(s) such as stroke, brain tumor, schizophrenia, epilepsy, normal pressure hydrocephalus, mental retardation, brain trauma with unconsciousness, or a history of brain surgery causing unrecovered deficiency 5. Patients with severe extrapyramidal disorders (Hoehn and Hahr staging score ≥ IV) 6. Patients whose systolic blood pressure was less than 90 mmHg or pulse rate was less than 50 bpm at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Mini-Mental State Examination (MMSE) Score | Week 12 for Confirmatory Phase | 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. Data are presented as change from baseline in mean MMSE +/- standard deviation. |
| Change From Baseline in Neuropsychiatric Inventory (NPI-2) Score | Week 12 for Confirmatory Phase | The NPI was a questionnaire that quantified psychiatric symptoms and behavioral disorders in dementia. A total of 12 items (the original NPI-10 consisting of 10 behavioral domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor behavior, supplemented by 2 dementia with Lewy bodies (DLB)-relevant domains of sleep, and cognitive fluctuation \[reported as cognitive fluctuation inventory\]) were assessed. The score of each item was calculated as frequency (scale: 1=occasionally to 4=very frequently) x Severity (scale: 1=Mild to 3=Severe). The NPI-2 was calculated as the sum of the scores for hallucinations and cognitive fluctuation, to yield a possible total score of 0 to 24. Lower score=less severity. A negative change score from baseline indicated improvement. Data are presented as change from baseline in mean NPI-2 +/- standard deviation. |
Countries
Japan
Participant flow
Pre-assignment details
In the 'Placebo to Donepezil (5+10 mg) Extension Phase' arm, 37 of 46 participants started active treatment at Week 16.
Participants by arm
| Arm | Count |
|---|---|
| Placebo - Confirmatory Phase Participants received donepezil matched placebo tablets orally, once daily for 12 weeks in the confirmatory phase. | 44 |
| Donepezil 5 mg - Confirmatory Phase Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 10 weeks in the confirmatory phase. | 45 |
| Donepezil 10 mg - Confirmatory Phase Participants received donepezil tablets orally, once daily for 12 weeks. Treatment began with 3 mg for 2 weeks, and then the dose was increased to 5 mg for 4 weeks. Thereafter, the dose was increased to 10 mg for 6 weeks in the confirmatory phase. | 49 |
| Total | 138 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Confirmatory Phase | Adverse Event | 5 | 10 | 1 | 0 | 0 |
| Confirmatory Phase | Other | 1 | 1 | 2 | 0 | 0 |
| Confirmatory Phase | Participant's Choice | 3 | 5 | 3 | 0 | 0 |
| Extension Phase | Adverse Event | 0 | 0 | 0 | 7 | 16 |
| Extension Phase | Other | 0 | 0 | 0 | 1 | 3 |
| Extension Phase | Participant's Choice | 0 | 0 | 0 | 4 | 11 |
Baseline characteristics
| Characteristic | Placebo - Confirmatory Phase | Donepezil 5 mg - Confirmatory Phase | Donepezil 10 mg - Confirmatory Phase | Total |
|---|---|---|---|---|
| Age, Continuous | 77.2 Years STANDARD_DEVIATION 6.1 | 78.8 Years STANDARD_DEVIATION 5.1 | 77.7 Years STANDARD_DEVIATION 6.8 | 77.9 Years STANDARD_DEVIATION 6.1 |
| Mini-Mental State Examination (MMSE) Score | 20.3 Unit on a scale STANDARD_DEVIATION 4.2 | 20.6 Unit on a scale STANDARD_DEVIATION 4.1 | 20.3 Unit on a scale STANDARD_DEVIATION 4.8 | 20.4 Unit on a scale STANDARD_DEVIATION 4.3 |
| Sex: Female, Male Female | 27 Participants | 25 Participants | 28 Participants | 80 Participants |
| Sex: Female, Male Male | 17 Participants | 20 Participants | 21 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 23 / 46 | 18 / 47 | 17 / 49 | 31 / 37 | 62 / 96 |
| serious Total, serious adverse events | 5 / 46 | 4 / 47 | 1 / 49 | 9 / 37 | 12 / 96 |
Outcome results
Primary
Change From Baseline in 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. Data are presented as change from baseline in mean MMSE +/- standard deviation.
Time frame: Week 12 for Confirmatory Phase
Population: Full Analysis Set: Efficacy was analyzed in the full analysis set, including the randomized participants who received the study drug at least once and had valid efficacy assessment data at more than one point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Confirmatory Phase | Change From Baseline in Mini-Mental State Examination (MMSE) Score | 0.6 Units on a scale | Standard Deviation 3 |
| Donepezil 5 mg - Confirmatory Phase | Change From Baseline in Mini-Mental State Examination (MMSE) Score | 1.4 Units on a scale | Standard Deviation 3.4 |
| Donepezil 10 mg - Confirmatory Phase | Change From Baseline in Mini-Mental State Examination (MMSE) Score | 2.2 Units on a scale | Standard Deviation 2.9 |
Primary
Change From Baseline in Neuropsychiatric Inventory (NPI-2) Score
The NPI was a questionnaire that quantified psychiatric symptoms and behavioral disorders in dementia. A total of 12 items (the original NPI-10 consisting of 10 behavioral domains: delusions, hallucinations, agitation/aggression, dysphoria, anxiety, euphoria, apathy, disinhibition, irritability/lability, and aberrant motor behavior, supplemented by 2 dementia with Lewy bodies (DLB)-relevant domains of sleep, and cognitive fluctuation \[reported as cognitive fluctuation inventory\]) were assessed. The score of each item was calculated as frequency (scale: 1=occasionally to 4=very frequently) x Severity (scale: 1=Mild to 3=Severe). The NPI-2 was calculated as the sum of the scores for hallucinations and cognitive fluctuation, to yield a possible total score of 0 to 24. Lower score=less severity. A negative change score from baseline indicated improvement. Data are presented as change from baseline in mean NPI-2 +/- standard deviation.
Time frame: Week 12 for Confirmatory Phase
Population: Full Analysis Set: Efficacy was analyzed in the full analysis set, including the randomized participants who received the study drug at least once and had valid efficacy assessment data at more than one point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo - Confirmatory Phase | Change From Baseline in Neuropsychiatric Inventory (NPI-2) Score | -2.0 Units on a scale | Standard Deviation 4.2 |
| Donepezil 5 mg - Confirmatory Phase | Change From Baseline in Neuropsychiatric Inventory (NPI-2) Score | -1.7 Units on a scale | Standard Deviation 4.3 |
| Donepezil 10 mg - Confirmatory Phase | Change From Baseline in Neuropsychiatric Inventory (NPI-2) Score | -2.9 Units on a scale | Standard Deviation 4.7 |