Alzheimer's Disease
Conditions
Brief summary
This study will evaluate the performance of the CogState computerized neuropsychological battery, Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) and Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) in participants with mild-to-moderate Alzheimer's disease (AD).
Interventions
DRUGComparator: Placebo 5mg (run in)
Matching placebo to donepezil - 5 mg capsules orally for 14 day run in prior to randomization.
DRUGDonepezil 5 - 10 mg
Donepezil 1 capsule (5 mg) orally, once daily for 14 days. Donepezil 2 capsules (total 10 mg) once daily for 70 days (days 15-84).
DRUGComparator: Placebo 5-10 mg
Matching placebo to donepezil, 1 capsule (5 mg) orally, once daily for 14 days. Matching placebo to donepezil 2 capsules (total 10 mg) once daily for 70 days (days 15-84).
DRUGDonepezil 10 mg
Donepezil 2 capsules (total 10 mg) orally, once daily for 24 weeks, from day 85 (optional).
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant is ambulatory, male or female and 55 years of age or older * Participant has reliable informant/caregiver who can communicate effectively with the study site and personnel
Exclusion criteria
* Participant has a history within the last 6 months or current evidence of a psychotic disorder or an active major depressive disorder or participant has any history of schizophrenia * Participant has a history of multiple and/or serious allergies to drugs or food or a history of an allergic reaction to more than 3 drug classes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Computer-based Cognitive Assessment (CogState) Composite Score at Week 4 | Baseline and 4 weeks | CogState is a simple, brief computerized neuropsychological battery to evaluate cognitive impairments characterizing mild-to-moderate Alzheimer's Disease (AD). The composite CogState assesses attention and memory functions - including Verbal episodic memory, Visual Episodic Memory, Psychomotor function, Visual attention and working memory. CogState scores are measured on a linear scale (with no maximum score) and a reduction in scores compared to baseline indicates an improvement in cognitive functions. Reported here is the change in the CogState Composite Score at Week 4 compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate the Efficacy of Donepezil by Determining the Change in Mean CogState Composite Score at Week 2, Week 8 and Week 12 | Baseline and 2 weeks, 8 weeks and 12 weeks | CogState is a simple, brief computerized neuropsychological battery to evaluate cognitive impairments characterizing mild-to-moderate Alzheimer's Disease (AD). The composite CogState assesses attention and memory functions - including Verbal episodic memory, Visual Episodic Memory, Psychomotor function, Visual attention and working memory. CogState scores are measured on a linear scale (no maximum score) and a reduction in scores compared to baseline indicates an improvement in cognitive functions. Reported here is the change from baseline in the CogState Composite Score at Weeks 4, 8 and 12. |
| Evaluate the Efficacy of Donepezil by Determining the Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score at Week 4, Week 8 and Week 12 | Baseline and 4 weeks, 8 weeks and 12 weeks. | The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation and praxis using an 11-point AD Assessment Scale. It has a minimum score of 0 and a maximum severity score of 70, and a higher score indicates more impairment. A reduction in scores compared to baseline indicates an improvement in cognitive functions. Reported here is the change in the ADAS-Cog score at Weeks 4, 8 and 12 compared to baseline. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Donepezil 5-10 mg Participants were randomized to donepezil for 84 days | 53 |
| Placebo Participants were randomized to placebo for 84 days | 53 |
| Total | 106 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Investigator Decision | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Donepezil 5-10 mg | Placebo | Total |
|---|---|---|---|
| Age, Customized | 53 Participants | 53 Participants | 106 Participants |
| Sex: Female, Male Female | 23 Participants | 22 Participants | 45 Participants |
| Sex: Female, Male Male | 30 Participants | 31 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 10 / 53 | 9 / 53 |
| serious Total, serious adverse events | 3 / 53 | 0 / 53 |
Outcome results
Primary
Change in Mean Computer-based Cognitive Assessment (CogState) Composite Score at Week 4
CogState is a simple, brief computerized neuropsychological battery to evaluate cognitive impairments characterizing mild-to-moderate Alzheimer's Disease (AD). The composite CogState assesses attention and memory functions - including Verbal episodic memory, Visual Episodic Memory, Psychomotor function, Visual attention and working memory. CogState scores are measured on a linear scale (with no maximum score) and a reduction in scores compared to baseline indicates an improvement in cognitive functions. Reported here is the change in the CogState Composite Score at Week 4 compared to baseline.
Time frame: Baseline and 4 weeks
Population: The analysis for the primary and secondary CogState endpoints was done on a per protocol basis (only participants who were compliant and successfully tolerated the forced titration after 2 weeks of treatment were included in the analysis).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Donepezil 5-10 mg | Change in Mean Computer-based Cognitive Assessment (CogState) Composite Score at Week 4 | -0.10 Score on a scale | Standard Error 0.07 |
| Placebo | Change in Mean Computer-based Cognitive Assessment (CogState) Composite Score at Week 4 | -0.07 Score on a scale | Standard Error 0.06 |
p-value: 0.23190% CI: [-0.2, 0.08]ANOVA
Secondary
Evaluate the Efficacy of Donepezil by Determining the Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score at Week 4, Week 8 and Week 12
The ADAS-Cog is a psychometric instrument that evaluates memory, attention, reasoning, language, orientation and praxis using an 11-point AD Assessment Scale. It has a minimum score of 0 and a maximum severity score of 70, and a higher score indicates more impairment. A reduction in scores compared to baseline indicates an improvement in cognitive functions. Reported here is the change in the ADAS-Cog score at Weeks 4, 8 and 12 compared to baseline.
Time frame: Baseline and 4 weeks, 8 weeks and 12 weeks.
Population: The analysis for the primary and secondary CogState endpoints was done on a per protocol basis (only participants who were compliant and successfully tolerated the forced titration after 2 weeks of treatment were included in the analysis).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil 5-10 mg | Evaluate the Efficacy of Donepezil by Determining the Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score at Week 4, Week 8 and Week 12 | Week 8 (N=37, N=40) | 0.07 Score on a scale | Standard Error 1 |
| Donepezil 5-10 mg | Evaluate the Efficacy of Donepezil by Determining the Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score at Week 4, Week 8 and Week 12 | Week 12 (N=38, N=40) | -1.4 Score on a scale | Standard Error 1 |
| Donepezil 5-10 mg | Evaluate the Efficacy of Donepezil by Determining the Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score at Week 4, Week 8 and Week 12 | Week 4 (N=38, N=43) | 0.2 Score on a scale | Standard Error 0.8 |
| Placebo | Evaluate the Efficacy of Donepezil by Determining the Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score at Week 4, Week 8 and Week 12 | Week 4 (N=38, N=43) | -0.3 Score on a scale | Standard Error 0.7 |
| Placebo | Evaluate the Efficacy of Donepezil by Determining the Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score at Week 4, Week 8 and Week 12 | Week 8 (N=37, N=40) | -0.7 Score on a scale | Standard Error 1 |
| Placebo | Evaluate the Efficacy of Donepezil by Determining the Change in Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) Score at Week 4, Week 8 and Week 12 | Week 12 (N=38, N=40) | -1.0 Score on a scale | Standard Error 1 |
p-value: 0.32490% CI: [-1.2, 2.2]ANOVA
p-value: 0.28590% CI: [-1.5, 3.1]ANOVA
p-value: 0.40190% CI: [-2.6, 1.9]ANOVA
Secondary
Evaluate the Efficacy of Donepezil by Determining the Change in Mean CogState Composite Score at Week 2, Week 8 and Week 12
CogState is a simple, brief computerized neuropsychological battery to evaluate cognitive impairments characterizing mild-to-moderate Alzheimer's Disease (AD). The composite CogState assesses attention and memory functions - including Verbal episodic memory, Visual Episodic Memory, Psychomotor function, Visual attention and working memory. CogState scores are measured on a linear scale (no maximum score) and a reduction in scores compared to baseline indicates an improvement in cognitive functions. Reported here is the change from baseline in the CogState Composite Score at Weeks 4, 8 and 12.
Time frame: Baseline and 2 weeks, 8 weeks and 12 weeks
Population: The analysis for the primary and secondary CogState endpoints was done on a per protocol basis (only participants who were compliant and successfully tolerated the forced titration after 2 weeks of treatment were included in the analysis).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Donepezil 5-10 mg | Evaluate the Efficacy of Donepezil by Determining the Change in Mean CogState Composite Score at Week 2, Week 8 and Week 12 | Week 2 (N=38, N=43) | -0.2 Score on a scale | Standard Error 0.07 |
| Donepezil 5-10 mg | Evaluate the Efficacy of Donepezil by Determining the Change in Mean CogState Composite Score at Week 2, Week 8 and Week 12 | Week 8 (N=38, N=40) | -0.1 Score on a scale | Standard Error 0.07 |
| Donepezil 5-10 mg | Evaluate the Efficacy of Donepezil by Determining the Change in Mean CogState Composite Score at Week 2, Week 8 and Week 12 | Week 12 (N=38, N=41) | -0.2 Score on a scale | Standard Error 0.07 |
| Placebo | Evaluate the Efficacy of Donepezil by Determining the Change in Mean CogState Composite Score at Week 2, Week 8 and Week 12 | Week 8 (N=38, N=40) | -0.02 Score on a scale | Standard Error 0.07 |
| Placebo | Evaluate the Efficacy of Donepezil by Determining the Change in Mean CogState Composite Score at Week 2, Week 8 and Week 12 | Week 12 (N=38, N=41) | -0.09 Score on a scale | Standard Error 0.07 |
| Placebo | Evaluate the Efficacy of Donepezil by Determining the Change in Mean CogState Composite Score at Week 2, Week 8 and Week 12 | Week 2 (N=38, N=43) | -0.006 Score on a scale | Standard Error 0.06 |
p-value: 0.04190% CI: [-0.3, -0.008]ANOVA
p-value: 0.14390% CI: [-0.3, 0.06]ANOVA
p-value: 0.22690% CI: [-0.2, 0.09]ANOVA