Alzheimer Disease
Conditions
Brief summary
The study will evaluate the efficacy and safety of an investigational drug called SAM-531 at three dosage levels. Subjects will receive either one of the 3 dosage levels of SAM-531, donepezil or placebo for the first 24 weeks of the study (period I). Subjects who receive placebo for period I will be assigned to receive the highest dose of SAM-531 SAM-531 for the remaining 28 weeks of the study, while subjects who received one of the three SAM-531 dosage levels or donepezil in period I will continue with the same study drug (period II).
Detailed description
The study was stopped (date of termination was 13April2011) due to a 6 month interim analysis: all of the 3 SAM-531 dosage levels were declared futile. There were no safety concerns.
Interventions
DRUGPlacebo
Capsules SAM-531 placebo and 5 mg tablet encapsulated Donepezil placebo capsules, once a day during 24 weeks.
DRUGSAM-531 1.5 mg
Capsules SAM-531 1.5 mg, once a day during 52 weeks.
DRUGSAM-531 3.0 mg
Capsules SAM-531 3.0 mg, once a day during 52 weeks.
DRUGSAM-531 5.0 mg
Capsules SAM-531 5.0 mg, once a day during 24 weeks or 52 weeks.
DRUGDonepezil
Encapsulated Donepezil 5 mg tablets, once a day during 52 weeks. After Day 42, the dose can up titrated up to 10 mg of Donepezil.
Sponsors
Pfizer
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
* Diagnosis of probable Alzheimer Disease according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Diseases and Related Disorders Association (NINCDS-ADRDA) criteria. * Mini-Mental State Examination (MMSE) score of 12 to 24 at screening * Rosen Modified Hachinski Ischemic score \< or equal to 4 at screening.
Exclusion criteria
* Relevant neurologic disease other than Alzheimer Disease that may affect cognition or ability to complete the study. * Current major depressive disorder or other current major psychiatric disorder. * History of clinically evident stroke or clinically important carotid or vertebrobasilar stenosis or plaque. * Use of prescription or nonprescription medications for cognitive enhancement (including memantine, ginkgo biloba, huperzine A, and cholinesterase inhibitors) within 3 months before the baseline visit.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Baseline, Week 24 | 14-item scale to assess severity of cognitive impairment in Alzheimer's Disease. Items: word recall, naming objects and fingers, following commands, constructional praxis, ideational praxis, orientation, word recognition, recall of test instructions, spoken language ability, word-finding difficulty, comprehension of spoken language, concentration/distractibility, number cancellation and executive maze. Rating scale ranged from 0 (not present) to 5 (severe). Total score was sum of individual scores (items 1-11) and ranged from 0 to 70 with higher scores indicating greater cognitive impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Baseline, Week 24 | Caregiver interview-based rating scale assessed 10 behavioral, 2 neurovegetative disturbances occurring in dementia: delusions, hallucination, agitation/aggression, depression, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability, aberrant motor behavior, appetite/eating disorders and sleep/nightime behavior disorders. Each symptom score derived by symptom frequency (1 \[occasionally\] to 4 \[very frequently\] \* symptom severity (1 \[mild\] to 3 \[severe\]) and ranged 0-12. Total score = sum of symptom scores; range 0-144, higher score indicating greater behavioral disturbances |
| Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | Baseline, Week 24 | Caregiver and participant interview-based tool to rate the overall impression of participant's clinical change of the disease over time. Areas covered in the interview include: relevant history, observation/evaluation, mental/cognitive state, behavior and functioning. Change categorized into 1 of 7 categories: marked improvement, moderate improvement, minimal improvement, no change, minimal worsening, moderate worsening, marked worsening. |
| Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Baseline, Week 24 | CANTAB PAL-assessed visual memory/new learning using one or more patterns randomly displayed in boxes on a screen. Participants were to touch the box where patterns first appeared. Stage 1 (practice) and difficulty increased Stage 2 (2 patterns) to Stage 6 (6 patterns). When all locations correctly identified moved to next Stage. Test terminated when a stage could not be completed in 6 attempts. Total Errors=total number of incorrect boxes chosen plus adjustment for estimated possible errors on problems, attempts, and recalls not reached. Total score 0 to 106, lower scores=better performance. |
| Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Baseline, Week 24 | CANTAB PAL-assessed visual memory/new learning using one or more patterns randomly displayed in boxes on a screen. Participants were to touch the box where patterns first appeared. Stage 1 (practice) and difficulty increased Stage 2 (2 patterns) to Stage 6 (6 patterns). When all locations correctly identified moved to next Stage. Test terminated when a stage could not be completed in 6 attempts. Total score was the number of patterns presented at last stage successfully completed and ranged from 2 to 6, higher scores indicated better performance. |
| Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Baseline, Week 24 | CANTAB PAL-assessed visual memory/new learning using one or more patterns randomly displayed in boxes on a screen. Participants were to touch the box where patterns first appeared. Stage 1 (practice) and difficulty increased Stage 2 (2 patterns) to Stage 6 (6 patterns). When all locations correctly identified moved to next Stage. Test terminated when a stage could not be completed in 6 attempts. Total score was the number of correct choices made on the first attempt at each Stage. Total score ranged from 0 to 20, higher scores indicated better performance. |
| Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Baseline, Week 24 | CANTAB-SWM assessed participant's retention of spatial information, ability to manipulate remembered items and strategize. Participant asked to find tokens in on-screen boxes, move them. Difficulty ranged 4-8 boxes to assess, 2 trials per assessment. Between errors: number of times participant revisited a box where a token previously found. In 4 box assessments the maximum number of errors per trial was 20. Test ended with 20 errors in a trial. Less than 20 errors in both trials the participant went to the next level of difficulty. Scores ranged from 0 to 39. Lower scores: better performance. |
| Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Baseline, Week 24 | CANTAB-SWM assessed participant's retention of spatial information, ability to manipulate remembered items and strategize. Participant asked to find tokens in on-screen boxes, move them. Difficulty ranged 4-8 boxes to assess, 2 trials per assessment. Between errors: number of times participant revisited a box where a token previously found. In 6 box assessments the maximum number of errors per trial was 30. Test ended with 30 errors in a trial. Less than 30 errors in both trials the participant went to the next level of difficulty. Scores ranged from 0 to 59. Lower scores: better performance. |
| Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Baseline, Week 24 | CANTAB-SWM assessed participant's retention of spatial information, ability to manipulate remembered items and strategize. Participant asked to find tokens in on-screen boxes, move them. Difficulty ranged 4-8 boxes to assess, 2 trials per assessment. Between errors: number of times participant revisited a box where a token previously found. In 8 box assessments the maximum number of errors per trial was 40. Test ended with 40 errors in a trial. Less than 40 errors in both trials the participant went to the next level of difficulty. Scores ranged from 0 to 79. Lower scores: better performance. |
| Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Baseline, Week 24 | CANTAB-SWM assessed participant's retention of spatial information, ability to manipulate remembered items and strategize. Participant was asked to find tokens in on-screen boxes and move them. Difficulty ranged from 4 to 8 box assessments, 2 trials for each assessment. Possible errors for each successful assessment: 4 box 0-38; 6 box 0-58; 8 box 0-78. Between Errors for N Boxes was the cumulative number of errors per each successful trial. Total scores ranged from 0 to 175. Lower scores indicated better performance. |
| Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Baseline, Week 24 | Caregiver interview-based instrument assessing 10 areas of activities of daily living (ADL) to measure participant's actual performance over the previous 2 weeks. Items included hygiene, dressing, continence, eating, meal preparation, telephoning, outings, finance/correspondence, medications and leisure/housework. Responses scored as 1 (yes) or 0 (no), response of Not Applicable was not scored. Total DAD score was sum of scores for 40 items, expressed as a percentage of the number of items answered yes or no. Total score ranged from 0 to 100, higher scores represented less disability in ADL. |
| Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Baseline, Week 24 | CANTAB-PRM assessed participant's visual pattern recognition memory in a 2-choice forced discrimination paradigm. Participants presented with a series of 12 visual patterns singly. In recognition phase, participants were required to choose between a pattern previously seen and a novel pattern. Patterns in the recognition phase appeared sequentially in reverse order on the screen. Assessment was repeated with 12 new patterns. Latency in correct responses ranged from 0 to infinity millisecond (msec), lower scores indicated better performance. |
| Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Baseline, Week 24 | CANTAB-PRM assessed participant's visual pattern recognition memory in a 2-choice forced discrimination paradigm. Participants presented with a series of 12 visual patterns singly. In recognition phase, participants were required to choose between a pattern previously seen and a novel pattern. Patterns in the recognition phase appeared sequentially in reverse order on the screen. Assessment was repeated with 12 new patterns. Correct response total expressed as a percentage, ranged from 0 to 100, higher scores indicated better performance. |
| Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Baseline, Week 24 | CANTAB-RTI assessed participant's reaction, movement time and vigilance during a 5-choice reaction time trial and to measure anticipatory/premature and perseverative responses. In the trial, a yellow spot appeared on a computer screen in 1 of 5 locations, the participant responded by letting go of a press pad and touching the screen where the spot appeared. 5-Choice Accuracy was the total number of trials where participant responded correctly. Total ranged from 0 to 30, higher score indicated better performance. |
| Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Baseline, Week 24 | CANTAB-RTI assessed participant's reaction, movement time and vigilance during 5-choice reaction time trial and also measured anticipatory/premature responses. In the test, a yellow spot appeared on a computer screen in 1 of 5 locations, the participant responded by letting go of a press pad and touching the screen where the spot appeared. 5-Choice Movement Time was the time from release of press pad to screen touch where the spot had been in trials the participant responded correctly. Possible score ranged from 100 to 5100 msec, lower score indicated better performance. |
| Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Baseline, Week 24 | CANTAB-RTI assessed participant's reaction, movement time and vigilance during 5-choice reaction time trial and also measured anticipatory/premature responses. In the test, a yellow spot appeared on a computer screen in 1 of 5 locations, the participant responded by letting go of a press pad and touching the screen where the spot appeared. 5-Choice Reaction Time was the time from appearance of yellow spot on computer screen to time to release press pad in trials the participant responded correctly. Total ranged from 100 to 5100 (maximum allowed) msec, lower score indicated better performance. |
| Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Baseline, Week 24 | CANTAB-RTI assessed participant's reaction, movement time and vigilance during simple (1 choice) reaction time trial and also measured anticipatory/premature responses. In the test, 1 yellow spot appeared on a computer screen in 1 location, the participant responded by letting go of a press pad and touching the screen where the spot appeared. Simple Movement Time was the time from release of press pad to touch the screen where the spot had been in trials the participant responded correctly. Total ranged from 100 to 5100 (maximum allowed) msec, lower score indicated better performance. |
| Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Baseline, Week 24 | CANTAB-RTI assessed participant's reaction, movement time and vigilance during simple (1 choice) reaction time trial and also measured anticipatory/premature responses. In the test, 1 yellow spot appeared on a computer screen in 1 location, the participant responded by letting go of a press pad and touching the screen where the spot appeared. Simple Reaction Time was the time from appearance of yellow spot on computer screen to time to release press pad in trials the participant responded correctly. Total ranged from 100 to 5100 (maximum allowed) msec, lower score indicated better performance. |
| Percentage of Participants Who Were Responders at Week 24 | Week 24 | Responder defined as a participant who demonstrated an improvement of at least 3 points from baseline in the ADAS-Cog total score and no worsening in the DAD total score and in ADCS-CGIC. Participants were considered a responder at Week 24 if all 3 criteria were met. |
| Change From Baseline in CANTAB SWM Strategy at Week 24 | Baseline, Week 24 | CANTAB-SWM assessed participant's ability to strategize. Participant was asked to find tokens in on-screen boxes and move them. Difficulty ranged from 4 to 8 box assessments, 2 trials per assessment. Strategy score was the number of unique boxes the participant searched in the two 6 and 8 box trials. 6 box trial scores ranged from 1 (1 box searched for all 6 tokens) to 6 (6 boxes searched for 6 tokens). 8 box trial score ranged from 1 (1 box searched) to 8 (8 boxes searched for 8 tokens). Total of the 4 trial scores ranged from 4 to 28. Lower score indicated better performance. |
Countries
Argentina, Chile, Colombia, Hong Kong, Japan, Mexico, New Zealand, Poland, Romania, Russia, South Africa, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo, Then SAM-531 Matching SAM-531 placebo capsule administered orally once daily (QD, morning) and matching encapsulated Donepezil placebo tablet QD (evening) for up to 24 weeks (Period 1). Then from Week 25 up to Week 52 (Period 2) participants received SAM-531 5.0 milligram (mg) capsule administered once daily (QD, morning) and matching encapsulated Donepezil placebo tablet administered QD (evening). From Week 7 until Week 52 (end of study), the evening dose in both period 1 and 2 could have been increased to 2 tablets and adjusted back to 1 tablet at the investigator's discretion. | 106 |
| SAM-531 (1.5 mg) SAM-531 1.5 mg capsule administered orally QD (morning) for up to 52 weeks. Matching encapsulated Donepezil placebo tablet administered QD (evening) for up to 52 weeks. From Week 7 until Week 52 (end of study), the evening dose could have been increased to 2 tablets and adjusted back to 1 tablet at the investigator's discretion. | 102 |
| SAM-531 (3.0 mg) SAM-531 3.0 mg capsule administered orally QD (morning) for up to 52 weeks. Matching encapsulated Donepezil placebo tablet administered orally QD (evening) for up to 52 weeks. From Week 7 until Week 52 (end of study), the evening dose could have been increased to 2 tablets and adjusted back to 1 tablet at the investigator's discretion. | 103 |
| SAM-531 (5.0 mg) SAM-531 5.0 mg capsule administered orally QD (morning) for up to 52 weeks. Matching encapsulated Donepezil placebo tablet administered orally QD (evening) for up to 52 weeks. From Week 7 until Week 52 (end of study), the evening dose could have been increased to 2 tablets and adjusted back to 1 tablet at the investigator's discretion. | 103 |
| Donepezil Matching SAM-531 placebo capsule administered orally (QD, morning) for up to 52 weeks. Encapsulated Donepezil 5 mg tablet administered orally (QD, evening) for up to 52 weeks. From Week 7 until Week 52 (end of study), the evening dose could have been increased to 2 tablets and adjusted back to 1 tablet at the investigator's discretion. | 104 |
| Total | 518 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| After Period 1, Prior to Period 2 | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| After Period 1, Prior to Period 2 | Other | 0 | 0 | 1 | 0 | 0 |
| After Period 1, Prior to Period 2 | Protocol Violation | 0 | 0 | 0 | 0 | 1 |
| After Period 1, Prior to Period 2 | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 |
| Period 1 | Adverse Event | 7 | 6 | 4 | 6 | 7 |
| Period 1 | Death | 0 | 0 | 0 | 0 | 1 |
| Period 1 | discontinued by sponsor | 2 | 1 | 2 | 1 | 1 |
| Period 1 | failed to return | 0 | 0 | 1 | 0 | 1 |
| Period 1 | investigator request | 0 | 1 | 0 | 0 | 0 |
| Period 1 | Lost to Follow-up | 2 | 1 | 3 | 2 | 3 |
| Period 1 | Other | 1 | 2 | 1 | 1 | 1 |
| Period 1 | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
| Period 1 | randomized and not treated | 1 | 3 | 1 | 1 | 2 |
| Period 1 | unsatisfactory response-efficacy | 2 | 0 | 0 | 0 | 0 |
| Period 1 | Withdrawal by Subject | 6 | 6 | 8 | 2 | 4 |
| Period 2 | Adverse Event | 3 | 3 | 5 | 2 | 5 |
| Period 2 | Death | 0 | 0 | 1 | 0 | 0 |
| Period 2 | discontinued by sponsor | 44 | 44 | 38 | 46 | 37 |
| Period 2 | failed to return | 2 | 0 | 0 | 0 | 0 |
| Period 2 | investigator request | 2 | 0 | 0 | 0 | 0 |
| Period 2 | Lost to Follow-up | 1 | 2 | 1 | 1 | 0 |
| Period 2 | Other | 1 | 1 | 3 | 1 | 1 |
| Period 2 | Protocol Violation | 1 | 0 | 1 | 1 | 1 |
| Period 2 | unsatisfactory response-efficacy | 2 | 1 | 0 | 0 | 0 |
| Period 2 | Withdrawal by Subject | 0 | 2 | 0 | 3 | 5 |
Baseline characteristics
| Characteristic | Placebo, Then SAM-531 | SAM-531 (1.5 mg) | SAM-531 (3.0 mg) | SAM-531 (5.0 mg) | Donepezil | Total |
|---|---|---|---|---|---|---|
| Age, Customized 50 to 65 years | 22 participants | 17 participants | 19 participants | 18 participants | 20 participants | 96 participants |
| Age, Customized 66 to 80 years | 59 participants | 60 participants | 54 participants | 66 participants | 66 participants | 305 participants |
| Age, Customized greater than 80 years | 25 participants | 25 participants | 30 participants | 19 participants | 18 participants | 117 participants |
| Sex: Female, Male Female | 72 Participants | 70 Participants | 71 Participants | 73 Participants | 70 Participants | 356 Participants |
| Sex: Female, Male Male | 34 Participants | 32 Participants | 32 Participants | 30 Participants | 34 Participants | 162 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 106 | 23 / 102 | 32 / 103 | 37 / 103 | 24 / 104 | 13 / 106 | 13 / 102 | 22 / 103 | 22 / 103 | 19 / 104 |
| serious Total, serious adverse events | 7 / 106 | 7 / 102 | 8 / 103 | 4 / 103 | 4 / 104 | 8 / 106 | 2 / 102 | 7 / 103 | 3 / 103 | 7 / 104 |
Outcome results
Primary
Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24
14-item scale to assess severity of cognitive impairment in Alzheimer's Disease. Items: word recall, naming objects and fingers, following commands, constructional praxis, ideational praxis, orientation, word recognition, recall of test instructions, spoken language ability, word-finding difficulty, comprehension of spoken language, concentration/distractibility, number cancellation and executive maze. Rating scale ranged from 0 (not present) to 5 (severe). Total score was sum of individual scores (items 1-11) and ranged from 0 to 70 with higher scores indicating greater cognitive impairment.
Time frame: Baseline, Week 24
Population: Intent to treat (ITT) population: randomized participants who took at least one dose of study medication, had a baseline evaluation and had at least one on-treatment post-baseline evaluation for the ADAS-Cog; Number of Participants Analyzed (N): number of evaluable participants
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Week 24 | 23.8 units on a scale | Standard Deviation 12 |
| Placebo, Then SAM-531 | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Baseline | 23.6 units on a scale | Standard Deviation 10.3 |
| SAM-531 (1.5 mg) | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Baseline | 24.1 units on a scale | Standard Deviation 11.7 |
| SAM-531 (1.5 mg) | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Week 24 | 24.2 units on a scale | Standard Deviation 13.1 |
| SAM-531 (3.0 mg) | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Baseline | 23.6 units on a scale | Standard Deviation 10.6 |
| SAM-531 (3.0 mg) | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Week 24 | 23.5 units on a scale | Standard Deviation 12 |
| SAM-531 (5.0 mg) | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Baseline | 22.6 units on a scale | Standard Deviation 9.8 |
| SAM-531 (5.0 mg) | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Week 24 | 21.9 units on a scale | Standard Deviation 10.6 |
| Donepezil | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Week 24 | 22.4 units on a scale | Standard Deviation 10.9 |
| Donepezil | Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24 | Baseline | 23.4 units on a scale | Standard Deviation 10 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.42495% CI: [-1, 2.3]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.84995% CI: [-1.8, 1.5]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.5295% CI: [-2.2, 1.1]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.25895% CI: [-2.6, 0.7]Mixed Models Analysis
Secondary
Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24
CANTAB PAL-assessed visual memory/new learning using one or more patterns randomly displayed in boxes on a screen. Participants were to touch the box where patterns first appeared. Stage 1 (practice) and difficulty increased Stage 2 (2 patterns) to Stage 6 (6 patterns). When all locations correctly identified moved to next Stage. Test terminated when a stage could not be completed in 6 attempts. Total Errors=total number of incorrect boxes chosen plus adjustment for estimated possible errors on problems, attempts, and recalls not reached. Total score 0 to 106, lower scores=better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Baseline | 68.3 errors | Standard Deviation 27.4 |
| Placebo, Then SAM-531 | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Week 24 | 66.4 errors | Standard Deviation 27.4 |
| SAM-531 (1.5 mg) | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Baseline | 66.9 errors | Standard Deviation 29.6 |
| SAM-531 (1.5 mg) | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Week 24 | 68.1 errors | Standard Deviation 29.2 |
| SAM-531 (3.0 mg) | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Baseline | 66.5 errors | Standard Deviation 28.6 |
| SAM-531 (3.0 mg) | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Week 24 | 67.5 errors | Standard Deviation 29.8 |
| SAM-531 (5.0 mg) | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Week 24 | 64.9 errors | Standard Deviation 30.8 |
| SAM-531 (5.0 mg) | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Baseline | 67.6 errors | Standard Deviation 28.8 |
| Donepezil | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Baseline | 67.8 errors | Standard Deviation 29.3 |
| Donepezil | Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24 | Week 24 | 66.7 errors | Standard Deviation 28.6 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.55395% CI: [-3.9, 7.3]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.88695% CI: [-6, 5.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.71295% CI: [-6.6, 4.5]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.78595% CI: [-4.8, 6.4]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24
CANTAB PAL-assessed visual memory/new learning using one or more patterns randomly displayed in boxes on a screen. Participants were to touch the box where patterns first appeared. Stage 1 (practice) and difficulty increased Stage 2 (2 patterns) to Stage 6 (6 patterns). When all locations correctly identified moved to next Stage. Test terminated when a stage could not be completed in 6 attempts. Total score was the number of correct choices made on the first attempt at each Stage. Total score ranged from 0 to 20, higher scores indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Baseline | 4.6 correct choices | Standard Deviation 3.9 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Week 24 | 4.8 correct choices | Standard Deviation 4 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Baseline | 4.8 correct choices | Standard Deviation 4.5 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Week 24 | 4.4 correct choices | Standard Deviation 4.2 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Baseline | 4.7 correct choices | Standard Deviation 4.3 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Week 24 | 4.8 correct choices | Standard Deviation 4.5 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Week 24 | 5.1 correct choices | Standard Deviation 4.5 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Baseline | 4.6 correct choices | Standard Deviation 4.1 |
| Donepezil | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Baseline | 4.6 correct choices | Standard Deviation 4.4 |
| Donepezil | Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24 | Week 24 | 4.5 correct choices | Standard Deviation 4.1 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.3495% CI: [-1.5, 0.5]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.6395% CI: [-0.8, 1.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.67895% CI: [-0.8, 1.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.51895% CI: [-1.3, 0.7]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24
CANTAB PAL-assessed visual memory/new learning using one or more patterns randomly displayed in boxes on a screen. Participants were to touch the box where patterns first appeared. Stage 1 (practice) and difficulty increased Stage 2 (2 patterns) to Stage 6 (6 patterns). When all locations correctly identified moved to next Stage. Test terminated when a stage could not be completed in 6 attempts. Total score was the number of patterns presented at last stage successfully completed and ranged from 2 to 6, higher scores indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Baseline | 4.1 patterns | Standard Deviation 1.3 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Week 24 | 4.3 patterns | Standard Deviation 1.3 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Baseline | 4.2 patterns | Standard Deviation 1.3 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Week 24 | 4.1 patterns | Standard Deviation 1.4 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Baseline | 4.2 patterns | Standard Deviation 1.3 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Week 24 | 4.2 patterns | Standard Deviation 1.4 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Week 24 | 4.2 patterns | Standard Deviation 1.5 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Baseline | 4.1 patterns | Standard Deviation 1.4 |
| Donepezil | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Baseline | 4.1 patterns | Standard Deviation 1.3 |
| Donepezil | Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24 | Week 24 | 4.2 patterns | Standard Deviation 1.4 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.25195% CI: [-0.5, 0.1]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.99395% CI: [-0.3, 0.3]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.55395% CI: [-0.4, 0.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.61195% CI: [-0.4, 0.2]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24
CANTAB-PRM assessed participant's visual pattern recognition memory in a 2-choice forced discrimination paradigm. Participants presented with a series of 12 visual patterns singly. In recognition phase, participants were required to choose between a pattern previously seen and a novel pattern. Patterns in the recognition phase appeared sequentially in reverse order on the screen. Assessment was repeated with 12 new patterns. Latency in correct responses ranged from 0 to infinity millisecond (msec), lower scores indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Baseline | 4583.7 msec | Standard Deviation 3121.2 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Week 24 | 4288.3 msec | Standard Deviation 2082.7 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Baseline | 4121.1 msec | Standard Deviation 2358.8 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Week 24 | 3979.1 msec | Standard Deviation 3002.3 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Baseline | 4973.4 msec | Standard Deviation 2784.3 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Week 24 | 3793.5 msec | Standard Deviation 1698 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Week 24 | 4301.5 msec | Standard Deviation 2931.4 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Baseline | 4216.4 msec | Standard Deviation 2208.6 |
| Donepezil | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Baseline | 4303.0 msec | Standard Deviation 2705.2 |
| Donepezil | Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24 | Week 24 | 4387.8 msec | Standard Deviation 2703.8 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.86195% CI: [-739.7, 618.8]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.00795% CI: [-1596.9, -256.3]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.67695% CI: [-522.1, 804.6]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.50595% CI: [-449.7, 910.9]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB PRM-Percentage Correct at Week 24
CANTAB-PRM assessed participant's visual pattern recognition memory in a 2-choice forced discrimination paradigm. Participants presented with a series of 12 visual patterns singly. In recognition phase, participants were required to choose between a pattern previously seen and a novel pattern. Patterns in the recognition phase appeared sequentially in reverse order on the screen. Assessment was repeated with 12 new patterns. Correct response total expressed as a percentage, ranged from 0 to 100, higher scores indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Baseline | 59.3 percentage of correct answers | Standard Deviation 18.7 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Week 24 | 59.4 percentage of correct answers | Standard Deviation 16.3 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Baseline | 62.2 percentage of correct answers | Standard Deviation 18.4 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Week 24 | 63.0 percentage of correct answers | Standard Deviation 20.2 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Baseline | 63.4 percentage of correct answers | Standard Deviation 17.1 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Week 24 | 64.4 percentage of correct answers | Standard Deviation 18.4 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Week 24 | 65.9 percentage of correct answers | Standard Deviation 17.6 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Baseline | 66.7 percentage of correct answers | Standard Deviation 17.7 |
| Donepezil | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Baseline | 63.9 percentage of correct answers | Standard Deviation 18.9 |
| Donepezil | Change From Baseline in CANTAB PRM-Percentage Correct at Week 24 | Week 24 | 63.7 percentage of correct answers | Standard Deviation 16.9 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.26795% CI: [-2.2, 7.8]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.14595% CI: [-1.3, 8.6]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.13995% CI: [-1.2, 8.6]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.38695% CI: [-2.8, 7.2]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24
CANTAB-RTI assessed participant's reaction, movement time and vigilance during a 5-choice reaction time trial and to measure anticipatory/premature and perseverative responses. In the trial, a yellow spot appeared on a computer screen in 1 of 5 locations, the participant responded by letting go of a press pad and touching the screen where the spot appeared. 5-Choice Accuracy was the total number of trials where participant responded correctly. Total ranged from 0 to 30, higher score indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Baseline | 27.3 correct trials | Standard Deviation 4.4 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Week 24 | 27.8 correct trials | Standard Deviation 3.2 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Baseline | 26.9 correct trials | Standard Deviation 5.8 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Week 24 | 26.7 correct trials | Standard Deviation 5.9 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Baseline | 27.0 correct trials | Standard Deviation 5.6 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Week 24 | 28.1 correct trials | Standard Deviation 4 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Week 24 | 28.1 correct trials | Standard Deviation 3.4 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Baseline | 28.1 correct trials | Standard Deviation 4.4 |
| Donepezil | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Baseline | 27.0 correct trials | Standard Deviation 5.4 |
| Donepezil | Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24 | Week 24 | 27.9 correct trials | Standard Deviation 4.6 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.03295% CI: [-2.3, -0.1]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.26495% CI: [-0.5, 1.7]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.89395% CI: [-1, 1.1]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.52595% CI: [-0.7, 1.4]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24
CANTAB-RTI assessed participant's reaction, movement time and vigilance during 5-choice reaction time trial and also measured anticipatory/premature responses. In the test, a yellow spot appeared on a computer screen in 1 of 5 locations, the participant responded by letting go of a press pad and touching the screen where the spot appeared. 5-Choice Movement Time was the time from release of press pad to screen touch where the spot had been in trials the participant responded correctly. Possible score ranged from 100 to 5100 msec, lower score indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Baseline | 573.5 msec | Standard Deviation 218.6 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Week 24 | 539.9 msec | Standard Deviation 199 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Baseline | 583.1 msec | Standard Deviation 307.5 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Week 24 | 578.8 msec | Standard Deviation 290.9 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Baseline | 617.6 msec | Standard Deviation 381.9 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Week 24 | 584.7 msec | Standard Deviation 284.9 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Week 24 | 546.4 msec | Standard Deviation 191 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Baseline | 564.4 msec | Standard Deviation 310 |
| Donepezil | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Baseline | 583.6 msec | Standard Deviation 292.8 |
| Donepezil | Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24 | Week 24 | 560.6 msec | Standard Deviation 284.6 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.05695% CI: [-1.6, 123.5]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.48895% CI: [-40, 83.5]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.78395% CI: [-52.6, 69.8]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.57895% CI: [-44.6, 79.8]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24
CANTAB-RTI assessed participant's reaction, movement time and vigilance during 5-choice reaction time trial and also measured anticipatory/premature responses. In the test, a yellow spot appeared on a computer screen in 1 of 5 locations, the participant responded by letting go of a press pad and touching the screen where the spot appeared. 5-Choice Reaction Time was the time from appearance of yellow spot on computer screen to time to release press pad in trials the participant responded correctly. Total ranged from 100 to 5100 (maximum allowed) msec, lower score indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Baseline | 488.6 msec | Standard Deviation 275.8 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Week 24 | 447.3 msec | Standard Deviation 139.3 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Baseline | 503.7 msec | Standard Deviation 215.2 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Week 24 | 483.6 msec | Standard Deviation 211.3 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Baseline | 488.6 msec | Standard Deviation 200.8 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Week 24 | 473.7 msec | Standard Deviation 184.4 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Week 24 | 438.5 msec | Standard Deviation 170.7 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Baseline | 438.2 msec | Standard Deviation 172.1 |
| Donepezil | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Baseline | 475.7 msec | Standard Deviation 205.9 |
| Donepezil | Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24 | Week 24 | 443.3 msec | Standard Deviation 145.5 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.17595% CI: [-13.9, 76.1]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.35295% CI: [-23.3, 65.4]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.79795% CI: [-38.1, 49.6]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.63395% CI: [-55.6, 33.9]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB RTI Simple Movement Time at Week 24
CANTAB-RTI assessed participant's reaction, movement time and vigilance during simple (1 choice) reaction time trial and also measured anticipatory/premature responses. In the test, 1 yellow spot appeared on a computer screen in 1 location, the participant responded by letting go of a press pad and touching the screen where the spot appeared. Simple Movement Time was the time from release of press pad to touch the screen where the spot had been in trials the participant responded correctly. Total ranged from 100 to 5100 (maximum allowed) msec, lower score indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Baseline | 620.4 msec | Standard Deviation 299 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Week 24 | 585.2 msec | Standard Deviation 253.2 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Baseline | 631.2 msec | Standard Deviation 379.2 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Week 24 | 630.6 msec | Standard Deviation 359.5 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Baseline | 669.0 msec | Standard Deviation 473.8 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Week 24 | 641.8 msec | Standard Deviation 366.4 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Week 24 | 604.6 msec | Standard Deviation 262.2 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Baseline | 641.2 msec | Standard Deviation 443 |
| Donepezil | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Baseline | 624.0 msec | Standard Deviation 336 |
| Donepezil | Change From Baseline in CANTAB RTI Simple Movement Time at Week 24 | Week 24 | 621.0 msec | Standard Deviation 331.8 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.06695% CI: [-4.7, 147]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.59895% CI: [-54.6, 94.7]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.76695% CI: [-62.9, 85.3]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.37895% CI: [-41.5, 109.1]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24
CANTAB-RTI assessed participant's reaction, movement time and vigilance during simple (1 choice) reaction time trial and also measured anticipatory/premature responses. In the test, 1 yellow spot appeared on a computer screen in 1 location, the participant responded by letting go of a press pad and touching the screen where the spot appeared. Simple Reaction Time was the time from appearance of yellow spot on computer screen to time to release press pad in trials the participant responded correctly. Total ranged from 100 to 5100 (maximum allowed) msec, lower score indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Baseline | 471.8 msec | Standard Deviation 219.7 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Week 24 | 449.2 msec | Standard Deviation 195.8 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Baseline | 510.9 msec | Standard Deviation 295.1 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Week 24 | 479.7 msec | Standard Deviation 327.7 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Baseline | 487.1 msec | Standard Deviation 255.1 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Week 24 | 460.4 msec | Standard Deviation 213.5 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Week 24 | 445.3 msec | Standard Deviation 206 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Baseline | 442.8 msec | Standard Deviation 247.3 |
| Donepezil | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Baseline | 501.3 msec | Standard Deviation 302.9 |
| Donepezil | Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24 | Week 24 | 445.5 msec | Standard Deviation 203.6 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.48195% CI: [-40.2, 85.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.89495% CI: [-57.5, 65.9]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.99195% CI: [-61.5, 60.8]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.42295% CI: [-87.9, 36.9]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24
CANTAB-SWM assessed participant's retention of spatial information, ability to manipulate remembered items and strategize. Participant asked to find tokens in on-screen boxes, move them. Difficulty ranged 4-8 boxes to assess, 2 trials per assessment. Between errors: number of times participant revisited a box where a token previously found. In 4 box assessments the maximum number of errors per trial was 20. Test ended with 20 errors in a trial. Less than 20 errors in both trials the participant went to the next level of difficulty. Scores ranged from 0 to 39. Lower scores: better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Baseline | 3.8 errors | Standard Deviation 2 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Week 24 | 3.7 errors | Standard Deviation 2.3 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Baseline | 3.6 errors | Standard Deviation 2.4 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Week 24 | 3.6 errors | Standard Deviation 2.3 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Baseline | 3.8 errors | Standard Deviation 2.7 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Week 24 | 3.7 errors | Standard Deviation 2.5 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Week 24 | 3.1 errors | Standard Deviation 2.3 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Baseline | 3.5 errors | Standard Deviation 2.1 |
| Donepezil | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Baseline | 3.9 errors | Standard Deviation 2.4 |
| Donepezil | Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24 | Week 24 | 3.5 errors | Standard Deviation 2.3 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.95395% CI: [-0.7, 0.7]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.95695% CI: [-0.7, 0.6]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.21695% CI: [-1.1, 0.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.66595% CI: [-0.8, 0.5]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24
CANTAB-SWM assessed participant's retention of spatial information, ability to manipulate remembered items and strategize. Participant asked to find tokens in on-screen boxes, move them. Difficulty ranged 4-8 boxes to assess, 2 trials per assessment. Between errors: number of times participant revisited a box where a token previously found. In 6 box assessments the maximum number of errors per trial was 30. Test ended with 30 errors in a trial. Less than 30 errors in both trials the participant went to the next level of difficulty. Scores ranged from 0 to 59. Lower scores: better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Baseline | 9.2 errors | Standard Deviation 3.9 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Week 24 | 8.9 errors | Standard Deviation 2.9 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Baseline | 9.1 errors | Standard Deviation 4.2 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Week 24 | 9.2 errors | Standard Deviation 4.9 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Baseline | 9.1 errors | Standard Deviation 3.9 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Week 24 | 9.0 errors | Standard Deviation 4.1 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Week 24 | 9.1 errors | Standard Deviation 3.9 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Baseline | 8.6 errors | Standard Deviation 4 |
| Donepezil | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Baseline | 10.0 errors | Standard Deviation 4.8 |
| Donepezil | Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24 | Week 24 | 8.9 errors | Standard Deviation 3.7 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.37395% CI: [-0.6, 1.7]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.78195% CI: [-1, 1.3]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.41795% CI: [-0.7, 1.6]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.85395% CI: [-1.3, 1]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24
CANTAB-SWM assessed participant's retention of spatial information, ability to manipulate remembered items and strategize. Participant asked to find tokens in on-screen boxes, move them. Difficulty ranged 4-8 boxes to assess, 2 trials per assessment. Between errors: number of times participant revisited a box where a token previously found. In 8 box assessments the maximum number of errors per trial was 40. Test ended with 40 errors in a trial. Less than 40 errors in both trials the participant went to the next level of difficulty. Scores ranged from 0 to 79. Lower scores: better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Week 24 | 21.1 errors | Standard Deviation 5.6 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Baseline | 20.7 errors | Standard Deviation 5.9 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Week 24 | 20.0 errors | Standard Deviation 6.4 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Baseline | 20.1 errors | Standard Deviation 5.8 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Week 24 | 20.8 errors | Standard Deviation 5.4 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Baseline | 20.8 errors | Standard Deviation 6.1 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Baseline | 19.3 errors | Standard Deviation 6.9 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Week 24 | 19.7 errors | Standard Deviation 7.1 |
| Donepezil | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Week 24 | 19.8 errors | Standard Deviation 5.8 |
| Donepezil | Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24 | Baseline | 20.2 errors | Standard Deviation 6.5 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.42895% CI: [-2.6, 1.1]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.76395% CI: [-2.1, 1.5]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.31295% CI: [-2.7, 0.9]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.21595% CI: [-3, 0.7]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24
CANTAB-SWM assessed participant's retention of spatial information, ability to manipulate remembered items and strategize. Participant was asked to find tokens in on-screen boxes and move them. Difficulty ranged from 4 to 8 box assessments, 2 trials for each assessment. Possible errors for each successful assessment: 4 box 0-38; 6 box 0-58; 8 box 0-78. Between Errors for N Boxes was the cumulative number of errors per each successful trial. Total scores ranged from 0 to 175. Lower scores indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Baseline | 33.8 errors | Standard Deviation 9 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Week 24 | 33.8 errors | Standard Deviation 7.8 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Baseline | 32.8 errors | Standard Deviation 9.4 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Week 24 | 32.8 errors | Standard Deviation 10.3 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Baseline | 33.7 errors | Standard Deviation 10 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Week 24 | 33.5 errors | Standard Deviation 9.6 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Week 24 | 32.0 errors | Standard Deviation 10.2 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Baseline | 31.4 errors | Standard Deviation 8.9 |
| Donepezil | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Baseline | 34.2 errors | Standard Deviation 10.4 |
| Donepezil | Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24 | Week 24 | 32.2 errors | Standard Deviation 9.5 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.2895% CI: [-4, 1.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.95695% CI: [-2.7, 2.5]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.98895% CI: [-2.6, 2.5]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.8995% CI: [-2.7, 2.4]Mixed Models Analysis
Secondary
Change From Baseline in CANTAB SWM Strategy at Week 24
CANTAB-SWM assessed participant's ability to strategize. Participant was asked to find tokens in on-screen boxes and move them. Difficulty ranged from 4 to 8 box assessments, 2 trials per assessment. Strategy score was the number of unique boxes the participant searched in the two 6 and 8 box trials. 6 box trial scores ranged from 1 (1 box searched for all 6 tokens) to 6 (6 boxes searched for 6 tokens). 8 box trial score ranged from 1 (1 box searched) to 8 (8 boxes searched for 8 tokens). Total of the 4 trial scores ranged from 4 to 28. Lower score indicated better performance.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in CANTAB SWM Strategy at Week 24 | Baseline | 19.7 boxes | Standard Deviation 3.1 |
| Placebo, Then SAM-531 | Change From Baseline in CANTAB SWM Strategy at Week 24 | Week 24 | 20.0 boxes | Standard Deviation 2.2 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB SWM Strategy at Week 24 | Baseline | 19.4 boxes | Standard Deviation 3.3 |
| SAM-531 (1.5 mg) | Change From Baseline in CANTAB SWM Strategy at Week 24 | Week 24 | 19.1 boxes | Standard Deviation 3.3 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB SWM Strategy at Week 24 | Baseline | 19.2 boxes | Standard Deviation 2.8 |
| SAM-531 (3.0 mg) | Change From Baseline in CANTAB SWM Strategy at Week 24 | Week 24 | 19.4 boxes | Standard Deviation 2.3 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB SWM Strategy at Week 24 | Week 24 | 19.0 boxes | Standard Deviation 3.9 |
| SAM-531 (5.0 mg) | Change From Baseline in CANTAB SWM Strategy at Week 24 | Baseline | 19.1 boxes | Standard Deviation 3.6 |
| Donepezil | Change From Baseline in CANTAB SWM Strategy at Week 24 | Baseline | 19.0 boxes | Standard Deviation 3.6 |
| Donepezil | Change From Baseline in CANTAB SWM Strategy at Week 24 | Week 24 | 20.0 boxes | Standard Deviation 2 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.15495% CI: [-1.5, 0.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.7495% CI: [-1, 0.7]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.17995% CI: [-1.4, 0.3]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.54395% CI: [-0.6, 1.1]Mixed Models Analysis
Secondary
Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24
Caregiver interview-based instrument assessing 10 areas of activities of daily living (ADL) to measure participant's actual performance over the previous 2 weeks. Items included hygiene, dressing, continence, eating, meal preparation, telephoning, outings, finance/correspondence, medications and leisure/housework. Responses scored as 1 (yes) or 0 (no), response of Not Applicable was not scored. Total DAD score was sum of scores for 40 items, expressed as a percentage of the number of items answered yes or no. Total score ranged from 0 to 100, higher scores represented less disability in ADL.
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Baseline | 77.4 percentage of yes answers | Standard Deviation 21.8 |
| Placebo, Then SAM-531 | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Week 24 | 76.7 percentage of yes answers | Standard Deviation 24.2 |
| SAM-531 (1.5 mg) | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Baseline | 73.1 percentage of yes answers | Standard Deviation 20.9 |
| SAM-531 (1.5 mg) | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Week 24 | 71.4 percentage of yes answers | Standard Deviation 25 |
| SAM-531 (3.0 mg) | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Baseline | 72.9 percentage of yes answers | Standard Deviation 22.5 |
| SAM-531 (3.0 mg) | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Week 24 | 73.0 percentage of yes answers | Standard Deviation 24.4 |
| SAM-531 (5.0 mg) | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Week 24 | 76.8 percentage of yes answers | Standard Deviation 23.1 |
| SAM-531 (5.0 mg) | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Baseline | 75.5 percentage of yes answers | Standard Deviation 21 |
| Donepezil | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Baseline | 73.2 percentage of yes answers | Standard Deviation 22.9 |
| Donepezil | Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24 | Week 24 | 75.6 percentage of yes answers | Standard Deviation 24.5 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.36795% CI: [-5.2, 1.9]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.9195% CI: [-3.3, 3.7]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.1695% CI: [-1, 6]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.0695% CI: [-0.1, 6.9]Mixed Models Analysis
Secondary
Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24
Caregiver interview-based rating scale assessed 10 behavioral, 2 neurovegetative disturbances occurring in dementia: delusions, hallucination, agitation/aggression, depression, anxiety, elation/euphoria, apathy/indifference, disinhibition, irritability, aberrant motor behavior, appetite/eating disorders and sleep/nightime behavior disorders. Each symptom score derived by symptom frequency (1 \[occasionally\] to 4 \[very frequently\] \* symptom severity (1 \[mild\] to 3 \[severe\]) and ranged 0-12. Total score = sum of symptom scores; range 0-144, higher score indicating greater behavioral disturbances
Time frame: Baseline, Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo, Then SAM-531 | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Baseline | 10.6 unit on a scale | Standard Deviation 13.9 |
| Placebo, Then SAM-531 | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Week 24 | 10.7 unit on a scale | Standard Deviation 14.4 |
| SAM-531 (1.5 mg) | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Baseline | 14.6 unit on a scale | Standard Deviation 16.6 |
| SAM-531 (1.5 mg) | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Week 24 | 11.9 unit on a scale | Standard Deviation 14.6 |
| SAM-531 (3.0 mg) | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Baseline | 14.8 unit on a scale | Standard Deviation 18.1 |
| SAM-531 (3.0 mg) | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Week 24 | 9.7 unit on a scale | Standard Deviation 11.3 |
| SAM-531 (5.0 mg) | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Week 24 | 10.4 unit on a scale | Standard Deviation 11.4 |
| SAM-531 (5.0 mg) | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Baseline | 13.4 unit on a scale | Standard Deviation 13.4 |
| Donepezil | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Baseline | 12.1 unit on a scale | Standard Deviation 14.8 |
| Donepezil | Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24 | Week 24 | 9.3 unit on a scale | Standard Deviation 12.9 |
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.93195% CI: [-2.8, 3.1]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.05495% CI: [-5.8, 0.1]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.24695% CI: [-4.6, 1.2]Mixed Models Analysis
Comparison: Analysis of adjusted difference in change from baseline.p-value: 0.42695% CI: [-4.1, 1.7]Mixed Models Analysis
Secondary
Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24
Caregiver and participant interview-based tool to rate the overall impression of participant's clinical change of the disease over time. Areas covered in the interview include: relevant history, observation/evaluation, mental/cognitive state, behavior and functioning. Change categorized into 1 of 7 categories: marked improvement, moderate improvement, minimal improvement, no change, minimal worsening, moderate worsening, marked worsening.
Time frame: Baseline, Week 24
Population: ITT; N=number of evaluable participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo, Then SAM-531 | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked improvement | 0 participants |
| Placebo, Then SAM-531 | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked worsening | 1 participants |
| Placebo, Then SAM-531 | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate worsening | 2 participants |
| Placebo, Then SAM-531 | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal improvement | 20 participants |
| Placebo, Then SAM-531 | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate improvement | 1 participants |
| Placebo, Then SAM-531 | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | no change | 32 participants |
| Placebo, Then SAM-531 | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal worsening | 30 participants |
| SAM-531 (1.5 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal worsening | 17 participants |
| SAM-531 (1.5 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | no change | 36 participants |
| SAM-531 (1.5 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate improvement | 2 participants |
| SAM-531 (1.5 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked improvement | 1 participants |
| SAM-531 (1.5 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate worsening | 5 participants |
| SAM-531 (1.5 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal improvement | 23 participants |
| SAM-531 (1.5 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked worsening | 1 participants |
| SAM-531 (3.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | no change | 33 participants |
| SAM-531 (3.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked improvement | 1 participants |
| SAM-531 (3.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate improvement | 5 participants |
| SAM-531 (3.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal improvement | 19 participants |
| SAM-531 (3.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal worsening | 19 participants |
| SAM-531 (3.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate worsening | 6 participants |
| SAM-531 (3.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked worsening | 1 participants |
| SAM-531 (5.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal improvement | 17 participants |
| SAM-531 (5.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal worsening | 22 participants |
| SAM-531 (5.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate improvement | 3 participants |
| SAM-531 (5.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked worsening | 0 participants |
| SAM-531 (5.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate worsening | 4 participants |
| SAM-531 (5.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked improvement | 1 participants |
| SAM-531 (5.0 mg) | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | no change | 45 participants |
| Donepezil | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal improvement | 23 participants |
| Donepezil | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked worsening | 1 participants |
| Donepezil | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate worsening | 3 participants |
| Donepezil | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | minimal worsening | 25 participants |
| Donepezil | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | moderate improvement | 4 participants |
| Donepezil | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | marked improvement | 1 participants |
| Donepezil | Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24 | no change | 30 participants |
p-value: 0.265Cochran-Mantel-Haenszel
p-value: 0.682Cochran-Mantel-Haenszel
p-value: 0.532Cochran-Mantel-Haenszel
p-value: 0.087Cochran-Mantel-Haenszel
p-value: 0.751Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Who Were Responders at Week 24
Responder defined as a participant who demonstrated an improvement of at least 3 points from baseline in the ADAS-Cog total score and no worsening in the DAD total score and in ADCS-CGIC. Participants were considered a responder at Week 24 if all 3 criteria were met.
Time frame: Week 24
Population: ITT; N=number of participants with evaluable data
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo, Then SAM-531 | Percentage of Participants Who Were Responders at Week 24 | 9.2 percentage of participants |
| SAM-531 (1.5 mg) | Percentage of Participants Who Were Responders at Week 24 | 7.1 percentage of participants |
| SAM-531 (3.0 mg) | Percentage of Participants Who Were Responders at Week 24 | 10.5 percentage of participants |
| SAM-531 (5.0 mg) | Percentage of Participants Who Were Responders at Week 24 | 15.2 percentage of participants |
| Donepezil | Percentage of Participants Who Were Responders at Week 24 | 20.7 percentage of participants |
p-value: 0.58195% CI: [0.24, 2.22]Regression, Logistic
p-value: 0.7795% CI: [0.42, 3.19]Regression, Logistic
p-value: 0.21695% CI: [0.71, 4.55]Regression, Logistic
p-value: 0.03795% CI: [1.06, 6.42]Regression, Logistic