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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01312896




Registration number
NCT01312896
Ethics application status
Date submitted
7/05/2009
Date registered
8/05/2009
Date last updated
31/01/2013

Titles & IDs
Public title
Study Comparing 3 Dosage Levels Of SAM-531 In Outpatients With Mild To Moderate Alzheimer Disease
Scientific title
A 52-Week, Two-Period, Multicenter, Randomized, Double-Blind, Donepezil-Referenced, Placebo-Controlled, Efficacy And Safety Study Of 3 Dosage Levels Of SAM-531 In Outpatients With Mild To Moderate Alzheimer Disease
Secondary ID [1] 0 0
B1961007
Secondary ID [2] 0 0
3193A1-2005
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Placebo
Treatment: Drugs - SAM-531 1.5 mg
Treatment: Drugs - SAM-531 3.0 mg
Treatment: Drugs - SAM-531 5.0 mg
Treatment: Drugs - Donepezil

Placebo comparator: 1 - Placebo

Experimental: 2 - SAM-531 1.5 mg

Experimental: 3 - SAM-531 3.0 mg

Experimental: 4 - SAM-531 5.0 mg

Active comparator: 5 - Donepezil


Treatment: Drugs: Placebo
Capsules SAM-531 placebo and 5 mg tablet encapsulated Donepezil placebo capsules, once a day during 24 weeks.

Treatment: Drugs: SAM-531 1.5 mg
Capsules SAM-531 1.5 mg, once a day during 52 weeks.

Treatment: Drugs: SAM-531 3.0 mg
Capsules SAM-531 3.0 mg, once a day during 52 weeks.

Treatment: Drugs: SAM-531 5.0 mg
Capsules SAM-531 5.0 mg, once a day during 24 weeks or 52 weeks.

Treatment: Drugs: Donepezil
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline in the Alzheimer's Disease Assessment Scale-Cognition (ADAS-Cog) Total Score at Week 24
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [1] 0 0
Change From Baseline in Disability Assessment for Dementia (DAD) Total Score at Week 24
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Change From Baseline in Neuropsychiatry Inventory (NPI) at Week 24
Assessment method [2] 0 0
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
Timepoint [2] 0 0
Baseline, Week 24
Secondary outcome [3] 0 0
Number of Participants With Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) Scores at Week 24
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Change From Baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL)Total Errors (N, Shapes, Adjusted) at Week 24
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Change From Baseline in CANTAB PAL - Number of Patterns Reached at Week 24
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Change From Baseline in CANTAB PAL - First Trial Memory Score, Patterns at Week 24
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Change From Baseline in CANTAB Spatial Working Memory (SWM) - Between Errors (4 Boxes) at Week 24
Assessment method [7] 0 0
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.
Timepoint [7] 0 0
Baseline, Week 24
Secondary outcome [8] 0 0
Change From Baseline in CANTAB-SWM - Between Errors (6 Boxes) at Week 24
Assessment method [8] 0 0
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.
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Change From Baseline in CANTAB SWM - Between Errors (8 Boxes) at Week 24
Assessment method [9] 0 0
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.
Timepoint [9] 0 0
Baseline, Week 24
Secondary outcome [10] 0 0
Change From Baseline in CANTAB SWM - Between Errors (N Boxes) at Week 24
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Change From Baseline in CANTAB SWM Strategy at Week 24
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
Baseline, Week 24
Secondary outcome [12] 0 0
Change From Baseline in CANTAB Pattern Recognition Memory (PRM)-Mean Correct Latency at Week 24
Assessment method [12] 0 0
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.
Timepoint [12] 0 0
Baseline, Week 24
Secondary outcome [13] 0 0
Change From Baseline in CANTAB PRM-Percentage Correct at Week 24
Assessment method [13] 0 0
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.
Timepoint [13] 0 0
Baseline, Week 24
Secondary outcome [14] 0 0
Change From Baseline in CANTAB Reaction Time (RTI) Five-Choice Accuracy at Week 24
Assessment method [14] 0 0
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.
Timepoint [14] 0 0
Baseline, Week 24
Secondary outcome [15] 0 0
Change From Baseline in CANTAB RTI Five-Choice Movement Time at Week 24
Assessment method [15] 0 0
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.
Timepoint [15] 0 0
Baseline, Week 24
Secondary outcome [16] 0 0
Change From Baseline in CANTAB RTI Five-Choice Reaction Time at Week 24
Assessment method [16] 0 0
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.
Timepoint [16] 0 0
Baseline, Week 24
Secondary outcome [17] 0 0
Change From Baseline in CANTAB RTI Simple Movement Time at Week 24
Assessment method [17] 0 0
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.
Timepoint [17] 0 0
Baseline, Week 24
Secondary outcome [18] 0 0
Change From Baseline in CANTAB RTI Simple Reaction Time at Week 24
Assessment method [18] 0 0
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.
Timepoint [18] 0 0
Baseline, Week 24
Secondary outcome [19] 0 0
Percentage of Participants Who Were Responders at Week 24
Assessment method [19] 0 0
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.
Timepoint [19] 0 0
Week 24

Eligibility
Key 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.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/05/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/05/2011
Sample size
Target
Accrual to date
Final
526
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oklahoma
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Vermont
Country [15] 0 0
United States of America
State/province [15] 0 0
Wisconsin
Country [16] 0 0
Argentina
State/province [16] 0 0
Buenos Aires
Country [17] 0 0
Argentina
State/province [17] 0 0
Ciudad de Buenos Aires
Country [18] 0 0
Chile
State/province [18] 0 0
Santiago
Country [19] 0 0
Chile
State/province [19] 0 0
Vina del Mar
Country [20] 0 0
Colombia
State/province [20] 0 0
Cundinamarca
Country [21] 0 0
Colombia
State/province [21] 0 0
Risaralda
Country [22] 0 0
Colombia
State/province [22] 0 0
Santander
Country [23] 0 0
Colombia
State/province [23] 0 0
Valle
Country [24] 0 0
Colombia
State/province [24] 0 0
Valle del Cauca
Country [25] 0 0
Hong Kong
State/province [25] 0 0
Hong Kong SAR, China
Country [26] 0 0
Hong Kong
State/province [26] 0 0
Hong Kong
Country [27] 0 0
Japan
State/province [27] 0 0
Tokyo
Country [28] 0 0
Japan
State/province [28] 0 0
Chiba
Country [29] 0 0
Japan
State/province [29] 0 0
Fukuoka
Country [30] 0 0
Japan
State/province [30] 0 0
Hiroshima
Country [31] 0 0
Japan
State/province [31] 0 0
Kanagawa
Country [32] 0 0
Japan
State/province [32] 0 0
Kumamoto
Country [33] 0 0
Japan
State/province [33] 0 0
Kyoto
Country [34] 0 0
Japan
State/province [34] 0 0
Nagano
Country [35] 0 0
Japan
State/province [35] 0 0
Nagasaki
Country [36] 0 0
Japan
State/province [36] 0 0
Shizuoka
Country [37] 0 0
Korea, Republic of
State/province [37] 0 0
Gyeonggi-do
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Seoul
Country [39] 0 0
Mexico
State/province [39] 0 0
Coahuila
Country [40] 0 0
Mexico
State/province [40] 0 0
Aguascalientes
Country [41] 0 0
New Zealand
State/province [41] 0 0
Auckland
Country [42] 0 0
New Zealand
State/province [42] 0 0
Hamilton
Country [43] 0 0
Poland
State/province [43] 0 0
Krakow
Country [44] 0 0
Poland
State/province [44] 0 0
Poznan
Country [45] 0 0
Poland
State/province [45] 0 0
Wroclaw
Country [46] 0 0
Romania
State/province [46] 0 0
Dolj
Country [47] 0 0
Romania
State/province [47] 0 0
Timis
Country [48] 0 0
Romania
State/province [48] 0 0
Bucuresti
Country [49] 0 0
Russian Federation
State/province [49] 0 0
Gatchina district, Leningrad region
Country [50] 0 0
Russian Federation
State/province [50] 0 0
Kazan
Country [51] 0 0
Russian Federation
State/province [51] 0 0
Moscow
Country [52] 0 0
Russian Federation
State/province [52] 0 0
Novosibirsk
Country [53] 0 0
Russian Federation
State/province [53] 0 0
Saint-Petersburg
Country [54] 0 0
Russian Federation
State/province [54] 0 0
Smolensk
Country [55] 0 0
Russian Federation
State/province [55] 0 0
Yaroslavl
Country [56] 0 0
South Africa
State/province [56] 0 0
Free State
Country [57] 0 0
South Africa
State/province [57] 0 0
Gauteng
Country [58] 0 0
South Africa
State/province [58] 0 0
Western Cape
Country [59] 0 0
South Africa
State/province [59] 0 0
Cape Town

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01312896