CompletedPhase 2Results posted

Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's Disease

Study AZ3110865, a Study Comparing SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's Disease

Lead sponsor

GlaxoSmithKline

Assets

Donepezil / Intepirdine

Listed sites

Recruiting sites

Enrollment

576

actual

Study population

Alzheimer’s disease

Key I/E criteria

•mild-to-moderate AD•Study partner/caregiver required

Primary endpoints

•ADAS-Cog•Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study IDAZ3110865

NCT IDNCT00708552

Timeline

Milestones

Study first posted2008-07-02estimated

Study start2008-07-04

Primary completion2010-03-01actual

Study completion2010-03-09actual

Results first posted2018-02-12actual

Last update posted2018-07-27actual

Assets

Drug assets

Donepezil Intepirdine

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age50 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Subjects and their caregivers must provide informed consent prior to study entry.

•Subjects must have a clinical diagnosis of probable mild-to-moderate Alzheimer's disease with a documented 6-month history of AD symptoms

•Subjects must have a regular caregiver who is willing to attend visits, oversee the subject's compliance with the study and report on the subject's status.

•Female subjects of child-bearing potential must agree to pregnancy testing and approved form of birth control

Exclusion criteria

•Diagnosis of possible, probable or definite vascular dementia.

•History/evidence of any other CNS disorder that could be interpreted as a cause of dementia

•History of known or suspected seizures, loss of consciousness or significant head trauma

•Subjects with ECG, blood pressure and laboratory values outside of protocol criteria are excluded.

•Subjects with known photosensitivity

•Subjects with a history of previous exposure to SB-742457, taking agents for which there is a theoretical risk of interaction with SB-742457, or taking medication for Alzheimer's disease or centrally acting agents which might impact study outcomes may not participate.

Endpoints (74)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Other (unclassified)

Safety / tolerability / PK

Behavior / neuropsychiatric

Function / daily living

Global cognition

26 endpoints

Primary/protocol endpoint

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=116 Participants	-0.3	0.56
SB-742457-15mgn=124 Participants	0.8	0.58
SB-742457-35mgn=115 Participants	0.4	0.62
Donepeziln=123 Participants	-0.5	0.45

Mean Difference (Net)1.195% CI-0.4 - 2.7p0.159Mixed model repeated measures

ADAS-Cog Total Score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)0.795% CI-0.9 - 2.3p0.410Mixed model repeated measures

ADAS-Cog Total Score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)-0.295% CI-1.6 - 1.2p0.821Mixed model repeated measures

ADAS-Cog Total Score, Placebo Vs Donepezil at Week 24

Secondary/protocol endpoint

Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline Mini Mental State Examination [MMSE] Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline [MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 24

Time frame:Baseline (Week 0) and Week 24

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 24

Time frame:Baseline (Week 0) and Week 24

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in ADAS-Cog Total Score at Week 12

Time frame:Baseline (Week 0) and Week 12

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in RBANS Total Score at Week 12

Time frame:Baseline (Week 0) and Week 12

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12

Time frame:Baseline (Week 0) and Week 12

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12

Time frame:Baseline (Week 0) and Week 12

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 12

Time frame:Week 12

Mini-Mental State Examination (MMSE)

descriptive

Secondary/protocol endpoint

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 12

Time frame:Week 12

Mini-Mental State Examination (MMSE)

descriptive

Secondary/protocol endpoint

Change From Baseline in MMSE Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=116 Participants	-2.3	1.44
SB-742457-15mgn=125 Participants	-4.0	1.42
SB-742457-35mgn=115 Participants	-4.4	1.49
Donepeziln=127 Participants	-0.3	1.21

Mean Difference (Net)-1.695% CI-5.6 - 2.3p0.423Mixed model repeated measures

RBANS Total Score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)-2.195% CI-6.1 - 1.9p0.305Mixed model repeated measures

RBANS Total Score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)2.095% CI-1.7 - 5.7p0.282Mixed model repeated measures

RBANS Total Score, Placebo Vs Donepezil at Week 24

Secondary/registry result

Time frame:Baseline (Week 0) and Week 24

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
PlaceboMMSE Score 16-26 on ADAS-Cog total scoren=88 Participants	-1.3	0.55
MMSE Score 16-26 on RBANS total scoren=87 Participants	-1.3	1.61
SB-742457-15mgMMSE Score 16-26 on ADAS-Cog total scoren=99 Participants	0.1	0.66
MMSE Score 16-26 on RBANS total scoren=100 Participants	-2.4	1.74
SB-742457-35mgMMSE Score 16-26 on ADAS-Cog total scoren=86 Participants	-0.4	0.73
MMSE Score 16-26 on RBANS total scoren=85 Participants	-2.8	1.82
DonepezilMMSE Score 16-26 on ADAS-Cog total scoren=94 Participants	-1.0	0.53
MMSE Score 16-26 on RBANS total scoren=95 Participants	1.1	1.52

Mean Difference (Net)1.495% CI-0.3 - 3.1p0.096Mixed model repeated measures

Baseline MMSE score of 16-26 on ADAS-Cog Total score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)1.095% CI-0.8 - 2.8p0.281Mixed model repeated measures

Baseline MMSE score of 16-26 on ADAS-Cog Total score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)0.495% CI-1.1 - 1.9p0.630Mixed model repeated measures

Baseline MMSE score of 16-26 on ADAS-Cog Total score, Placebo Vs Donepezil at Week 24

Mean Difference (Net)-1.195% CI-5.7 - 3.6p0.655Mixed model repeated measures

Baseline MMSE score of 16-26 on RBANS Total score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)-1.595% CI-6.2 - 3.3p0.545Mixed model repeated measures

Baseline MMSE score of 16-26 on RBANS Total score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)2.495% CI-1.9 - 6.8p0.270Mixed model repeated measures

Baseline MMSE score of 16-26 on RBANS Total score, Placebo Vs Donepezil at Week 24

Secondary/registry result

Time frame:Baseline (Week 0) and Week 24

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
PlaceboMMSE Score 10-20 on ADAS-Cog total scoren=77 Participants	0.0	0.71
MMSE Score 10-20 on RBANS total scoren=78 Participants	-3.7	1.79
SB-742457-15mgMMSE Score 10-20 on ADAS-Cog total scoren=80 Participants	1.6	0.76
MMSE Score 10-20 on RBANS total scoren=80 Participants	-5.8	1.73
SB-742457-35mgMMSE Score 10-20 on ADAS-Cog total scoren=78 Participants	1.3	0.73
MMSE Score 10-20 on RBANS total scoren=79 Participants	-4.8	1.68
DonepezilMMSE Score 10-20 on ADAS-Cog total scoren=81 Participants	-0.1	0.58
MMSE Score 10-20 on RBANS total scoren=85 Participants	-1.0	1.44

Mean Difference (Net)1.595% CI-0.5 - 3.6p0.138Mixed model repeated measures

Baseline MMSE score of 10-20 on ADAS-Cog Total score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)1.395% CI-0.7 - 3.2p0.216Mixed model repeated measures

Baseline MMSE score of 10-20 on ADAS-Cog Total score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)-0.195% CI-1.9 - 1.7p0.921Mixed model repeated measures

Baseline MMSE score of 10-20 on ADAS-Cog Total score, Placebo Vs Donepezil at Week 24

Mean Difference (Net)-2.195% CI-7.0 - 2.9p0.410Mixed model repeated measures

Baseline MMSE score of 10-20 on RBANS Total score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)-1.195% CI-5.9 - 3.8p0.667Mixed model repeated measures

Baseline MMSE score of 10-20 on RBANS Total score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)2.795% CI-1.9 - 7.2p0.246Mixed model repeated measures

Baseline MMSE score of 10-20 on RBANS Total score, Placebo Vs Donepezil at Week 24

Secondary/registry result

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 24

Time frame:Baseline (Week 0) and Week 24

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=88 Participants	3.8	0.12
SB-742457-15mgn=100 Participants	4.0	0.12
SB-742457-35mgn=87 Participants	3.7	0.11
Donepeziln=95 Participants	3.5	0.11

Mean Difference (Final Values)0.295% CI-0.1 - 0.6p0.146Mixed model repeated measures

Baseline MMSE score of 16-26 on CBIC+ score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Final Values)-0.195% CI-0.4 - 0.3p0.733Mixed model repeated measures

Baseline MMSE score of 16-26 on CBIC+ score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Final Values)-0.295% CI-0.5 - 0.1p0.145Mixed model repeated measures

Baseline MMSE score of 16-26 on CBIC+ score, Placebo Vs Donepezil at Week 24

Secondary/registry result

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 24

Time frame:Baseline (Week 0) and Week 24

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=79 Participants	4.2	0.15
SB-742457-15mgn=80 Participants	4.4	0.13
SB-742457-35mgn=80 Participants	4.1	0.12
Donepeziln=85 Participants	3.9	0.12

Mean Difference (Final Values)0.295% CI-0.2 - 0.6p0.295Mixed model repeated measures

Baseline MMSE score of 16-26 on CBIC+, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Final Values)-0.195% CI-0.5 - 0.2p0.495Mixed model repeated measures

Baseline MMSE score of 16-26 on CBIC+, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)-0.395% CI-0.6 - 0.1p0.166Mixed model repeated measures

Baseline MMSE score of 16-26 on CBIC+, Placebo Vs Donepezil at Week 24

Secondary/registry result

Change From Baseline in ADAS-Cog Total Score at Week 12

Time frame:Baseline (Week 0) and Week 12

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=124 Participants	-0.1	0.45
SB-742457-15mgn=133 Participants	0.0	0.46
SB-742457-35mgn=126 Participants	-0.2	0.45
Donepeziln=137 Participants	-0.6	0.40

Mean Difference (Net)0.195% CI-1.1 - 1.4p0.847Mixed model repeated measures

ADAS-Cog Total Score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)-0.195% CI-1.4 - 1.1p0.833Mixed Models Analysis

ADAS-Cog Total Score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)-0.595% CI-1.6 - 0.7p0.443Mixed model repeated measures

ADAS-Cog Total Score, Placebo Vs Donepzil at Week 12

Secondary/registry result

Change From Baseline in RBANS Total Score at Week 12

Time frame:Baseline (Week 0) and Week 12

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=125 Participants	-6.7	1.16
SB-742457-15mgn=134 Participants	-8.7	1.24
SB-742457-35mgn=125 Participants	-5.9	1.11
Donepeziln=138 Participants	-3.4	1.06

Mean Difference (Net)-1.995% CI-5.2 - 1.4p0.257Mixed model repeated measures

RBANS total score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)0.995% CI-2.2 - 4.0p0.570Mixed model repeated measures

RBANS total score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)3.495% CI0.3 - 6.4p0.031Mixed model repeated measures

RBANS total score, Placebo Vs Donepzil at Week 12

Secondary/registry result

Time frame:Baseline (Week 0) and Week 12

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
PlaceboMMSE Score 16-26 on ADAS-Cog total scoren=93 Participants	-0.6	0.48
MMSE Score 16-26 on RBANS total scoren=94 Participants	-7.5	1.28
SB-742457-15mgMMSE Score 16-26 on ADAS-Cog total scoren=104 Participants	-0.4	0.47
MMSE Score 16-26 on RBANS total scoren=104 Participants	-8.3	1.51
SB-742457-35mgMMSE Score 16-26 on ADAS-Cog total scoren=94 Participants	-0.5	0.52
MMSE Score 16-26 on RBANS total scoren=93 Participants	-4.4	1.35
DonepezilMMSE Score 16-26 on ADAS-Cog total scoren=106 Participants	-0.5	0.42
MMSE Score 16-26 on RBANS total scoren=106 Participants	-3.3	1.31

Mean Difference (Net)0.295% CI-1.1 - 1.5p0.798Mixed model repeated measures

Baseline MMSE score of 16-26 on ADAS-Cog Total score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)0.195% CI-1.3 - 1.4p0.918Mixed model repeated measures

Baseline MMSE score of 16-26 on ADAS-Cog Total score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)0.195% CI-1.2 - 1.3p0.924Mixed model repeated measures

Baseline MMSE score of 16-26 on ADAS-Cog Total score, Placebo Vs Donepezil at Week 12

Mean Difference (Net)-0.895% CI-4.7 - 3.0p0.676Mixed model repeated measures

Baseline MMSE score of 16-26 on RBANS Total score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)3.195% CI-0.4 - 6.7p0.086Mixed model repeated measures

Baseline MMSE score of 16-26 on RBANS Total score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)4.295% CI0.6 - 7.7p0.021Mixed model repeated measures

Baseline MMSE score of 16-26 on RBANS Total score, Placebo Vs Donepezil at Week 12

Secondary/registry result

Time frame:Baseline (Week 0) and Week 12

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
PlaceboMMSE Score 10-20 on ADAS-Cog total scoren=85 Participants	0.4	0.51
MMSE Score 10-20 on RBANS total scoren=85 Participants	-6.4	1.36
SB-742457-15mgMMSE Score 10-20 on ADAS-Cog total scoren=88 Participants	0.4	0.61
MMSE Score 10-20 on RBANS total scoren=89 Participants	-10.0	1.29
SB-742457-35mgMMSE Score 10-20 on ADAS-Cog total scoren=87 Participants	0.2	0.60
MMSE Score 10-20 on RBANS total scoren=87 Participants	-6.8	1.26
DonepezilMMSE Score 10-20 on ADAS-Cog total scoren=88 Participants	-0.9	0.51
MMSE Score 10-20 on RBANS total scoren=89 Participants	-1.7	1.20

Mean Difference (Net)0.195% CI-1.5 - 1.7p0.908Mixed model repeated measures

Baseline MMSE score of 10-20 on ADAS-Cog Total score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)-0.295% CI-1.7 - 1.4p0.826Mixed model repeated measures

Baseline MMSE score of 10-20 on ADAS-Cog Total score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)-1.295% CI-2.7 - 0.2p0.088Mixed model repeated measures

Baseline MMSE score of 10-20 on ADAS-Cog Total score, Placebo Vs Donepezil at Week 12

Mean Difference (Net)-3.695% CI-7.3 - 0.0p0.053Mixed model repeated measures

Baseline MMSE score of 10-20 on RBANS Total score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)-0.495% CI-4.0 - 3.3p0.848Mixed Models Analysis

Baseline MMSE score of 10-20 on RBANS Total score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)4.795% CI1.1 - 8.2p0.011Mixed model repeated measures

Baseline MMSE score of 10-20 on RBANS Total score, Placebo Vs Donepezil at Week 12

Secondary/registry result

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 12

Time frame:Week 12

Mini-Mental State Examination (MMSE)

descriptive

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=94 Participants	3.8	0.08
SB-742457-15mgn=104 Participants	3.8	0.09
SB-742457-35mgn=94 Participants	3.7	0.10
Donepeziln=107 Participants	3.6	0.08

Mean Difference (Net)0.195% CI-0.2 - 0.3p0.671Mixed model repeated measures

Baseline MMSE score of 16-26 on CIBIC+ score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)-0.195% CI-0.4 - 0.2p0.413Mixed model repeated measures

Baseline MMSE score of 16-26 on CIBIC+ Total score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)-0.195% CI-0.4 - 0.1p0.245Mixed model repeated measures

Baseline MMSE score of 16-26 on CIBIC+ Total score, Placebo Vs Donepezil at Week 12

Secondary/registry result

Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 12

Time frame:Week 12

Mini-Mental State Examination (MMSE)

descriptive

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=86 Participants	4.0	0.10
SB-742457-15mgn=88 Participants	4.1	0.10
SB-742457-35mgn=87 Participants	4.1	0.11
Donepeziln=90 Participants	3.7	0.11

Mean Difference (Net)0.195% CI-0.2 - 0.4p0.369Mixed model repeated measures

Baseline MMSE score of 10-20 on CIBIC+ score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)0.195% CI-0.2 - 0.4p0.550Mixed model repeated measures

Baseline MMSE score of 10-20 on CIBIC+ Total score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)-0.395% CI-0.5 - 0.0p0.082Mixed model repeated measures

Baseline MMSE score of 10-20 on CIBIC+ Total score, Placebo Vs Donepezil at Week 12

Secondary/registry result

Change From Baseline in MMSE Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=118 Participants	-0.3	0.29
SB-742457-15mgn=124 Participants	-0.3	0.28
SB-742457-35mgn=117 Participants	-0.1	0.29
Donepeziln=128 Participants	0.5	0.27

Mean Difference (Net)0.095% CI-0.8 - 0.8p0.966ANCOVA

MMSE Total score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)0.395% CI-0.5 - 1.1p0.505ANCOVA

MMSE Total score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)0.895% CI0.0 - 1.6p0.044ANCOVA

MMSE Total score, Placebo Vs Donepezil at Week 24

Function / daily living

4 endpoints

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score at Weeks 12 and 24

Time frame:Baseline (Week 0) and Weeks 12 and 24

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24

Time frame:Baseline (Week 0) and Weeks 12 and 24

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score at Weeks 12 and 24

Time frame:Baseline (Week 0) and Weeks 12 and 24

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
PlaceboADCS-ADL Total score at Week 12n=126 Participants	-0.4	0.59
ADCS-ADL Total score at Week 24n=118 Participants	-1.0	0.71
SB-742457-15mgADCS-ADL Total score at Week 12n=133 Participants	-1.1	0.65
ADCS-ADL Total score at Week 24n=123 Participants	-1.4	0.68
SB-742457-35mgADCS-ADL Total score at Week 12n=124 Participants	-0.1	0.64
ADCS-ADL Total score at Week 24n=114 Participants	-1.1	0.81
DonepezilADCS-ADL Total score at Week 12n=139 Participants	0.2	0.62
ADCS-ADL Total score at Week 24n=128 Participants	-1.2	0.82

Mean Difference (Net)-0.795% CI-2.4 - 1.0p0.417Mixed model repeated measures

ADCS-ADL Total score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)0.395% CI-1.4 - 2.0p0.725Mixed model repeated measures

ADCS-ADL Total score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)0.695% CI-1.1 - 2.2p0.506Mixed model repeated measures

ADCS-ADL Total score, Placebo Vs Donepezil at Week 12

Mean Difference (Net)-0.395% CI-2.3 - 1.6p0.723Mixed model repeated measures

ADCS-ADL Total score, Placebo Vs SB-742457-15mg at Week 24

Median Difference (Net)-0.195% CI-2.2 - 2.0p0.919Mixed model repeated measures

ADCS-ADL Total score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)-0.195% CI-2.3 - 2.0p0.896Mixed model repeated measures

ADCS-ADL Total score, Placebo Vs Donepezil at Week 24

Secondary/registry result

Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24

Time frame:Baseline (Week 0) and Weeks 12 and 24

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
PlaceboBasic score at Week 12n=126 Participants	-0.6	0.17
Basic score at Week 24n=118 Participants	-0.7	0.20
Instrumental score at Week 12n=126 Participants	0.2	0.50
Instrumental score at Week 24n=118 Participants	-0.3	0.60
Total Independence Score at Week 12n=126 Participants	-0.1	0.23
Total Independence Score at Week 24n=118 Participants	-0.3	0.27
SB-742457-15mgBasic score at Week 12n=133 Participants	-0.5	0.19
Basic score at Week 24n=123 Participants	-0.7	0.19
Instrumental score at Week 12n=133 Participants	-0.6	0.55
Instrumental score at Week 24n=124 Participants	-0.7	0.61
Total Independence Score at Week 12n=133 Participants	-0.1	0.23
Total Independence Score at Week 24n=124 Participants	-0.2	0.26
SB-742457-35mgBasic score at Week 12n=124 Participants	-0.4	0.24
Basic score at Week 24n=114 Participants	-0.6	0.24
Instrumental score at Week 12n=124 Participants	0.3	0.52
Instrumental score at Week 24n=114 Participants	-0.5	0.68
Total Independence Score at Week 12n=124 Participants	0.2	0.24
Total Independence Score at Week 24n=114 Participants	-0.1	0.29
DonepezilBasic score at Week 12n=139 Participants	-0.2	0.17
Basic score at Week 24n=128 Participants	-0.8	0.23
Instrumental score at Week 12n=139 Participants	0.4	0.55
Instrumental score at Week 24n=128 Participants	-0.4	0.70
Total Independence Score at Week 12n=139 Participants	0.2	0.23
Total Independence Score at Week 24n=128 Participants	-0.1	0.30

Mean Difference (Net)0.095% CI-0.5 - 0.5p0.869Mixed model repeated measures

Basic Score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)0.295% CI-0.4 - 0.8p0.500Mixed model repeated measures

Basic Score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)0.395% CI-0.1 - 0.8p0.140Mixed model repeated measures

Basic Score, Placebo Vs Donepezil at Week 12

Mean Difference (Net)0.095% CI-0.6 - 0.5p0.910Mixed model repeated measures

Basic Score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)0.195% CI-0.5 - 0.7p0.774Mixed model repeated measures

Basic Score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)-0.195% CI-0.7 - 0.5p0.726Mixed model repeated measures

Basic Score, Placebo Vs Donepezil at Week 24

Mean Difference (Net)-0.895% CI-2.2 - 0.7p0.292Mixed model repeated measures

Instrumental Score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)0.095% CI-1.3 - 1.4p0.946Mixed model repeated measures

Instrumental Score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)0.295% CI-1.3 - 1.6p0.802Mixed model repeated measures

Instrumental Score, Placebo Vs Donepezil at Week 12

Mean Difference (Net)-0.495% CI-2.1 - 1.3p0.636Mixed model repeated measures

Instrumental Score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)-0.395% CI-2.0 - 1.5p0.752Mixed model repeated measures

Instrumental Score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)-0.195% CI-1.9 - 1.7p0.920Mixed model repeated measures

Instrumental Score, Placebo Vs Donepezil at Week 24

Mean Difference (Net)0.095% CI-0.7 - 0.6p0.972Mixed model repeated measures

Total Independence Score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)0.395% CI-0.4 - 0.9p0.378Mixed model repeated measures

Total Independence Score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)0.395% CI-0.3 - 0.9p0.346Mixed model repeated measures

Total Independence Score, Placebo Vs Donepezil at Week 12

Mean Difference (Net)0.195% CI-0.6 - 0.9p0.720Mixed model repeated measures

Total Independence Score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)0.295% CI-0.6 - 1.0p0.598Mixed model repeated measures

Total Independence Score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)0.395% CI-0.5 - 1.1p0.480Mixed model repeated measures

Total Independence Score, Placebo Vs Donepezil at Week 24

Behavior / neuropsychiatric

6 endpoints

Primary/protocol endpoint

Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score at Week 24

Time frame:Week 24

descriptive

Primary/registry result

Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score at Week 24

Time frame:Week 24

descriptive

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=118 Participants	4.0	0.11
SB-742457-15mgn=125 Participants	4.2	0.10
SB-742457-35mgn=117 Participants	3.9	0.10
Donepeziln=127 Participants	3.7	0.10

Mean Difference (Net)0.295% CI-0.1 - 0.5p0.254Mixed model repeated measures

CIBIC+ Score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)-0.195% CI-0.4 - 0.2p0.394Mixed model repeated measures

CIBIC+ Score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)-0.395% CI-0.6 - -0.0p0.049Mixed model repeated measures

CIBIC+ Score, Placebo Vs Donepezil at Week 24

Secondary/protocol endpoint

CIBIC+ Score at Week 12

Time frame:Week 12

descriptive

Secondary/protocol endpoint

Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/registry result

CIBIC+ Score at Week 12

Time frame:Week 12

descriptive

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=126 Participants	3.9	0.08
SB-742457-15mgn=133 Participants	4.0	0.08
SB-742457-35mgn=126 Participants	3.9	0.09
Donepeziln=139 Participants	3.7	0.08

Mean Difference (Net)0.195% CI-0.1 - 0.3p0.320Mixed model repeated measures

CIBIC+ Score, Placebo Vs SB-742457-15mg at Week 12

Mean Difference (Net)0.095% CI-0.2 - 0.2p0.927Mixed model repeated measures

CIBIC+ Score, Placebo Vs SB-742457-35mg at Week 12

Mean Difference (Net)-0.295% CI-0.4 - 0.0p0.059Mixed model repeated measures

CIBIC+ Score, Placebo Vs Donepzil at Week 12

Secondary/registry result

Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) Total Score at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Placebon=118 Participants	0.0	0.26
SB-742457-15mgn=125 Participants	-0.1	0.25
SB-742457-35mgn=117 Participants	0.3	0.26
Donepeziln=128 Participants	0.3	0.25

Mean Difference (Net)-0.295% CI-0.9 - 0.5p0.594ANCOVA

CSDD Total score, Placebo Vs SB-742457-15mg at Week 24

Mean Difference (Net)0.295% CI-0.5 - 0.9p0.523ANCOVA

CSDD Total score, Placebo Vs SB-742457-35mg at Week 24

Mean Difference (Net)0.395% CI-0.4 - 1.0p0.429ANCOVA

CSDD Total score, Placebo Vs Donepezil at Week 24

Safety / tolerability / PK

12 endpoints

Secondary/protocol endpoint

Number of Participants With Any Adverse Event (Serious and Non-serious) and Serious Adverse Events (SAEs)

Time frame:Upto Week 24

event count, event

Secondary/protocol endpoint

Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT)

Time frame:Upto Week 24

event count, event

Secondary/protocol endpoint

Number of Participants With Electrocardiogram (ECG) Findings as Assessed by Investigator and Central Cardiologist

Time frame:Upto Week 24

event count, event

Secondary/protocol endpoint

Exposure Estimates for SB-742457 Area Under Curve Over the Dosing Interval at Steady State (AUCτss)

Time frame:One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose

concentration, descriptive

Secondary/protocol endpoint

Exposure Estimates for SB-742457 Minimum Concentration at Steady State (Cmin-ss)

Time frame:One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose

concentration, descriptive

Secondary/protocol endpoint

Exposure Estimates for Donepezil Average Concentration at Steady State (Cavgss)

Time frame:Weeks 4, 8,12,18 and Week 24

concentration, descriptive

Secondary/registry result

Number of Participants With Any Adverse Event (Serious and Non-serious) and Serious Adverse Events (SAEs)

Time frame:Upto Week 24

event count, event

Posted result

Group	Value (number), Participants	Reported bounds
PlaceboAny AEn=145 Participants	45	-
Any SAEn=145 Participants	7	-
SB-742457-15mgAny AEn=145 Participants	42	-
Any SAEn=145 Participants	7	-
SB-742457-35mgAny AEn=133 Participants	39	-
Any SAEn=133 Participants	3	-
DonepezilAny AEn=151 Participants	65	-
Any SAEn=151 Participants	10	-

Secondary/registry result

Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT)

Time frame:Upto Week 24

event count, event

Posted result

Group	Value (number), Participants	Reported bounds
PlaceboSBP sitting ATOT <90 or > 140 and IFB >=40n=140 Participants	1	-
SBP standing ATOT <90 or > 140 and IFB >=40n=140 Participants	0	-
SBP standing ATOT <90 or > 140 and DFB >=30n=140 Participants	0	-
SBP orthostatic, fall in SBP >30n=140 Participants	0	-
DBP sitting ATOT <50 or > 90 and IFB >=30n=140 Participants	0	-
DBP sitting ATOT <50 or > 90 and DFB >=20n=140 Participants	0	-
DBP standing ATOT <50 or > 90 and IFB >=30n=140 Participants	2	-
DBP standing ATOT <50 or > 90 and DFB >=20n=140 Participants	0	-
DBP orthostatic, fall in SBP >20n=140 Participants	0	-
HR sitting ATOT <50 or >100 and DFB >=30n=140 Participants	0	-
HR standing ATOT <50 or >100 and IFB >=30n=140 Participants	1	-
HR orthostatic, increase in HR>= >20n=140 Participants	5	-
Weight, IFB>=7%n=140 Participants	4	-
Weight, DFB>=7%n=140 Participants	6	-
SB-742457-15mgSBP sitting ATOT <90 or > 140 and IFB >=40n=143 Participants	2	-
SBP standing ATOT <90 or > 140 and IFB >=40n=143 Participants	3	-
SBP standing ATOT <90 or > 140 and DFB >=30n=143 Participants	0	-
SBP orthostatic, fall in SBP >30n=143 Participants	0	-
DBP sitting ATOT <50 or > 90 and IFB >=30n=143 Participants	0	-
DBP sitting ATOT <50 or > 90 and DFB >=20n=143 Participants	1	-
DBP standing ATOT <50 or > 90 and IFB >=30n=143 Participants	0	-
DBP standing ATOT <50 or > 90 and DFB >=20n=143 Participants	0	-
DBP orthostatic, fall in SBP >20n=143 Participants	0	-
HR sitting ATOT <50 or >100 and DFB >=30n=143 Participants	1	-
HR standing ATOT <50 or >100 and IFB >=30n=143 Participants	0	-
HR orthostatic, increase in HR>= >20n=143 Participants	2	-
Weight, IFB>=7%n=143 Participants	4	-
Weight, DFB>=7%n=143 Participants	8	-
SB-742457-35mgSBP sitting ATOT <90 or > 140 and IFB >=40n=133 Participants	2	-
SBP standing ATOT <90 or > 140 and IFB >=40n=133 Participants	3	-
SBP standing ATOT <90 or > 140 and DFB >=30n=133 Participants	0	-
SBP orthostatic, fall in SBP >30n=133 Participants	3	-
DBP sitting ATOT <50 or > 90 and IFB >=30n=133 Participants	1	-
DBP sitting ATOT <50 or > 90 and DFB >=20n=133 Participants	0	-
DBP standing ATOT <50 or > 90 and IFB >=30n=133 Participants	2	-
DBP standing ATOT <50 or > 90 and DFB >=20n=133 Participants	0	-
DBP orthostatic, fall in SBP >20n=133 Participants	1	-
HR sitting ATOT <50 or >100 and DFB >=30n=133 Participants	0	-
HR standing ATOT <50 or >100 and IFB >=30n=133 Participants	0	-
HR orthostatic, increase in HR>= >20n=133 Participants	2	-
Weight, IFB>=7%n=133 Participants	6	-
Weight, DFB>=7%n=133 Participants	5	-
DonepezilSBP sitting ATOT <90 or > 140 and IFB >=40n=149 Participants	0	-
SBP standing ATOT <90 or > 140 and IFB >=40n=149 Participants	1	-
SBP standing ATOT <90 or > 140 and DFB >=30n=149 Participants	4	-
SBP orthostatic, fall in SBP >30n=149 Participants	1	-
DBP sitting ATOT <50 or > 90 and IFB >=30n=149 Participants	1	-
DBP sitting ATOT <50 or > 90 and DFB >=20n=149 Participants	0	-
DBP standing ATOT <50 or > 90 and IFB >=30n=149 Participants	0	-
DBP standing ATOT <50 or > 90 and DFB >=20n=149 Participants	1	-
DBP orthostatic, fall in SBP >20n=149 Participants	1	-
HR sitting ATOT <50 or >100 and DFB >=30n=149 Participants	0	-
HR standing ATOT <50 or >100 and IFB >=30n=149 Participants	0	-
HR orthostatic, increase in HR>= >20n=149 Participants	6	-
Weight, IFB>=7%n=149 Participants	6	-
Weight, DFB>=7%n=149 Participants	10	-

Secondary/registry result

Number of Participants With Electrocardiogram (ECG) Findings as Assessed by Investigator and Central Cardiologist

Time frame:Upto Week 24

event count, event

Posted result

Group	Value (number), Participants	Reported bounds
PlaceboInvestigator interpretion ANCSn=121 Participants	58	-
Investigator interpretion ACSn=121 Participants	0	-
Central cardiologist interpretation abnormaln=120 Participants	49	-
SB-742457-15mgInvestigator interpretion ANCSn=131 Participants	60	-
Investigator interpretion ACSn=131 Participants	1	-
Central cardiologist interpretation abnormaln=131 Participants	51	-
SB-742457-35mgInvestigator interpretion ANCSn=119 Participants	59	-
Investigator interpretion ACSn=119 Participants	0	-
Central cardiologist interpretation abnormaln=119 Participants	51	-
DonepezilInvestigator interpretion ANCSn=134 Participants	67	-
Investigator interpretion ACSn=134 Participants	2	-
Central cardiologist interpretation abnormaln=136 Participants	59	-

Secondary/registry result

Exposure Estimates for SB-742457 Area Under Curve Over the Dosing Interval at Steady State (AUCτss)

Time frame:One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose

concentration, descriptive

Posted result

Group	Value (geometric_mean), nanograms hour per milliliter	Geometric coefficient of variation
SB-742457-15mgn=141 Participants	1434.89	36.04
SB-742457-35mgn=132 Participants	3424.91	38.04

Secondary/registry result

Exposure Estimates for SB-742457 Minimum Concentration at Steady State (Cmin-ss)

Time frame:One sample at Day 28±5, 56±5, 84±5, 126±5 and 168±5 post 24 hours of last dose

concentration, descriptive

Posted result

Group	Value (geometric_mean), nanograms per milliliter	Geometric coefficient of variation
SB-742457-15mgn=141 Participants	46.03	109.69
SB-742457-35mgn=132 Participants	37.47	39.47

Secondary/registry result

Exposure Estimates for Donepezil Average Concentration at Steady State (Cavgss)

Time frame:Weeks 4, 8,12,18 and Week 24

concentration, descriptive

Posted result

Group	Value (geometric_mean), nanograms per milliliter	Geometric coefficient of variation
Donepezil 5 mgn=132 Participants	17.53	50.51
Donepezil 10 mgn=133 Participants	31.80	60.14

Other (unclassified)

26 endpoints

Secondary/protocol endpoint/low confidence

Number of Participants With Hematology Data of PCC ATOT

Time frame:Upto Week 24

event count, event

Secondary/protocol endpoint/low confidence

Number of Participants With Chemistry Data of PCC ATOT

Time frame:Upto Week 24

event count, event

Secondary/protocol endpoint/low confidence

Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Clinical Chemistry Parameter Blood Urea Nitrogen /Creatinine Ratio at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Clinical Chemistry Parameters Creatinine, Direct Bilirubin and Total Bilirubin at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Hematology Parameter Hematocrit

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Hematology Parameters Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Hematology Parameter Mean Corpuscle Volume and Mean Platelet Volume at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change From Baseline in Hematology Parameter Red Blood Cell Count at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Secondary/registry result/low confidence

Number of Participants With Hematology Data of PCC ATOT

Time frame:Upto Week 24

event count, event

Posted result

Group	Value (number), Participants	Reported bounds
PlaceboHematocrit, ATOT, lown=138 Participants	1	-
Hemoglobin, ATOT. lown=138 Participants	2	-
Lymphocytes, ATOT, lown=138 Participants	4	-
Lymphocytes, ATOT, highn=138 Participants	0	-
Monocytes, ATOT, lown=138 Participants	17	-
Platelet count, ATOT, lown=138 Participants	3	-
Segmented neutrophils, ATOT, lown=138 Participants	2	-
Segmented neutrophils, ATOT, highn=138 Participants	1	-
Total neutrophils, ATOT, lown=138 Participants	2	-
Total neutrophils, ATOT, highn=138 Participants	0	-
White blood cell count, ATOT, lown=138 Participants	2	-
White blood cell count, ATOT, highn=138 Participants	0	-
SB-742457-15mgHematocrit, ATOT, lown=143 Participants	0	-
Hemoglobin, ATOT. lown=143 Participants	1	-
Lymphocytes, ATOT, lown=143 Participants	5	-
Lymphocytes, ATOT, highn=143 Participants	2	-
Monocytes, ATOT, lown=143 Participants	10	-
Platelet count, ATOT, lown=143 Participants	2	-
Segmented neutrophils, ATOT, lown=143 Participants	1	-
Segmented neutrophils, ATOT, highn=143 Participants	1	-
Total neutrophils, ATOT, lown=143 Participants	1	-
Total neutrophils, ATOT, highn=143 Participants	1	-
White blood cell count, ATOT, lown=143 Participants	0	-
White blood cell count, ATOT, highn=143 Participants	3	-
SB-742457-35mgHematocrit, ATOT, lown=132 Participants	0	-
Hemoglobin, ATOT. lown=132 Participants	2	-
Lymphocytes, ATOT, lown=132 Participants	3	-
Lymphocytes, ATOT, highn=132 Participants	0	-
Monocytes, ATOT, lown=132 Participants	9	-
Platelet count, ATOT, lown=131 Participants	2	-
Segmented neutrophils, ATOT, lown=132 Participants	0	-
Segmented neutrophils, ATOT, highn=132 Participants	1	-
Total neutrophils, ATOT, lown=132 Participants	0	-
Total neutrophils, ATOT, highn=132 Participants	1	-
White blood cell count, ATOT, lown=132 Participants	1	-
White blood cell count, ATOT, highn=132 Participants	1	-
DonepezilHematocrit, ATOT, lown=149 Participants	1	-
Hemoglobin, ATOT. lown=149 Participants	6	-
Lymphocytes, ATOT, lown=149 Participants	2	-
Lymphocytes, ATOT, highn=149 Participants	0	-
Monocytes, ATOT, lown=149 Participants	24	-
Platelet count, ATOT, lown=149 Participants	2	-
Segmented neutrophils, ATOT, lown=149 Participants	1	-
Segmented neutrophils, ATOT, highn=149 Participants	1	-
Total neutrophils, ATOT, lown=149 Participants	1	-
Total neutrophils, ATOT, highn=149 Participants	1	-
White blood cell count, ATOT, lown=149 Participants	1	-
White blood cell count, ATOT, highn=149 Participants	1	-

Secondary/registry result/low confidence

Number of Participants With Chemistry Data of PCC ATOT

Time frame:Upto Week 24

event count, event

Posted result

Group	Value (number), Participants	Reported bounds
PlaceboAlanine Amino Transferase, ATOT, highn=138 Participants	2	-
Alkaline Phosphatase, ATOT, highn=138 Participants	1	-
Aspartate Amino Transferase, ATOT, highn=138 Participants	0	-
Blood urea nitrogen/Creatinine ratio, ATOT, highn=138 Participants	1	-
Calcium, ATOT, lown=138 Participants	0	-
Carbon dioxide content/Bicarbonate, ATOT, lown=138 Participants	1	-
Cholesterol, ATOT, highn=120 Participants	5	-
Creatine Kinase, ATOT, highn=120 Participants	3	-
Creatinine, ATOT, highn=138 Participants	3	-
Direct Bilirubin, ATOT, highn=138 Participants	0	-
Gamma Glutamyl Transferase, ATOT, highn=138 Participants	3	-
Glucose, ATOT, lown=138 Participants	7	-
Glucose, ATOT, highn=138 Participants	27	-
Low Density Lipoprotein Cholesterol, ATOT, highn=117 Participants	21	-
Lactate Dehydrogenase, ATOT, highn=120 Participants	0	-
Potassium, ATOT, highn=138 Participants	5	-
Sodium, ATOT, lown=138 Participants	0	-
Sodium, ATOT, highn=138 Participants	0	-
Total Bilirubin, ATOT, highn=138 Participants	1	-
Triglycerides, ATOT, highn=120 Participants	0	-
Urea/Blood urea nitrogen, ATOT, highn=138 Participants	7	-
SB-742457-15mgAlanine Amino Transferase, ATOT, highn=142 Participants	0	-
Alkaline Phosphatase, ATOT, highn=142 Participants	0	-
Aspartate Amino Transferase, ATOT, highn=142 Participants	0	-
Blood urea nitrogen/Creatinine ratio, ATOT, highn=142 Participants	4	-
Calcium, ATOT, lown=142 Participants	0	-
Carbon dioxide content/Bicarbonate, ATOT, lown=142 Participants	0	-
Cholesterol, ATOT, highn=126 Participants	5	-
Creatine Kinase, ATOT, highn=126 Participants	1	-
Creatinine, ATOT, highn=142 Participants	1	-
Direct Bilirubin, ATOT, highn=142 Participants	0	-
Gamma Glutamyl Transferase, ATOT, highn=142 Participants	1	-
Glucose, ATOT, lown=142 Participants	5	-
Glucose, ATOT, highn=142 Participants	16	-
Low Density Lipoprotein Cholesterol, ATOT, highn=126 Participants	26	-
Lactate Dehydrogenase, ATOT, highn=126 Participants	1	-
Potassium, ATOT, highn=142 Participants	5	-
Sodium, ATOT, lown=142 Participants	2	-
Sodium, ATOT, highn=142 Participants	0	-
Total Bilirubin, ATOT, highn=142 Participants	1	-
Triglycerides, ATOT, highn=126 Participants	0	-
Urea/Blood urea nitrogen, ATOT, highn=142 Participants	6	-
SB-742457-35mgAlanine Amino Transferase, ATOT, highn=132 Participants	0	-
Alkaline Phosphatase, ATOT, highn=132 Participants	2	-
Aspartate Amino Transferase, ATOT, highn=132 Participants	0	-
Blood urea nitrogen/Creatinine ratio, ATOT, highn=132 Participants	0	-
Calcium, ATOT, lown=132 Participants	1	-
Carbon dioxide content/Bicarbonate, ATOT, lown=132 Participants	0	-
Cholesterol, ATOT, highn=118 Participants	2	-
Creatine Kinase, ATOT, highn=118 Participants	5	-
Creatinine, ATOT, highn=132 Participants	4	-
Direct Bilirubin, ATOT, highn=132 Participants	0	-
Gamma Glutamyl Transferase, ATOT, highn=132 Participants	4	-
Glucose, ATOT, lown=132 Participants	8	-
Glucose, ATOT, highn=132 Participants	23	-
Low Density Lipoprotein Cholesterol, ATOT, highn=117 Participants	12	-
Lactate Dehydrogenase, ATOT, highn=118 Participants	0	-
Potassium, ATOT, highn=132 Participants	2	-
Sodium, ATOT, lown=132 Participants	0	-
Sodium, ATOT, highn=132 Participants	0	-
Total Bilirubin, ATOT, highn=132 Participants	0	-
Triglycerides, ATOT, highn=118 Participants	0	-
Urea/Blood urea nitrogen, ATOT, highn=132 Participants	8	-
DonepezilAlanine Amino Transferase, ATOT, highn=149 Participants	1	-
Alkaline Phosphatase, ATOT, highn=149 Participants	6	-
Aspartate Amino Transferase, ATOT, highn=149 Participants	1	-
Blood urea nitrogen/Creatinine ratio, ATOT, highn=149 Participants	3	-
Calcium, ATOT, lown=149 Participants	0	-
Carbon dioxide content/Bicarbonate, ATOT, lown=149 Participants	0	-
Cholesterol, ATOT, highn=134 Participants	7	-
Creatine Kinase, ATOT, highn=134 Participants	7	-
Creatinine, ATOT, highn=149 Participants	1	-
Direct Bilirubin, ATOT, highn=149 Participants	1	-
Gamma Glutamyl Transferase, ATOT, highn=149 Participants	4	-
Glucose, ATOT, lown=149 Participants	6	-
Glucose, ATOT, highn=149 Participants	22	-
Low Density Lipoprotein Cholesterol, ATOT, highn=132 Participants	25	-
Lactate Dehydrogenase, ATOT, highn=134 Participants	0	-
Potassium, ATOT, highn=149 Participants	7	-
Sodium, ATOT, lown=149 Participants	0	-
Sodium, ATOT, highn=149 Participants	1	-
Total Bilirubin, ATOT, highn=149 Participants	2	-
Triglycerides, ATOT, highn=134 Participants	1	-
Urea/Blood urea nitrogen, ATOT, highn=149 Participants	4	-

Secondary/registry result/low confidence

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), IU/L	Standard deviation
PlaceboAlanine amino transferase at Week 24n=115 Participants	-0.3	8.76
Alkaline phosphatase at Week 24n=115 Participants	-3.4	15.71
Aspartate amino transferase at Week 24n=115 Participants	-0.3	6.15
Creatine kinase at Week 24n=111 Participants	-16.8	242.93
Gamma glutamyl transferase at Week 24n=115 Participants	-1.5	13.06
Lactate dehydrogenase at Week 24n=111 Participants	0.8	25.09
SB-742457-15mgAlanine amino transferase at Week 24n=121 Participants	0.0	4.88
Alkaline phosphatase at Week 24n=121 Participants	-0.1	10.91
Aspartate amino transferase at Week 24n=121 Participants	0.0	3.80
Creatine kinase at Week 24n=117 Participants	-5.4	47.97
Gamma glutamyl transferase at Week 24n=121 Participants	-0.2	11.23
Lactate dehydrogenase at Week 24n=117 Participants	-2.9	28.88
SB-742457-35mgAlanine amino transferase at Week 24n=116 Participants	-0.1	6.77
Alkaline phosphatase at Week 24n=116 Participants	0.8	14.63
Aspartate amino transferase at Week 24n=116 Participants	-0.1	6.88
Creatine kinase at Week 24n=115 Participants	16.2	157.67
Gamma glutamyl transferase at Week 24n=116 Participants	-1.3	15.08
Lactate dehydrogenase at Week 24n=115 Participants	-0.4	22.65
DonepezilAlanine amino transferase at Week 24n=127 Participants	1.6	29.47
Alkaline phosphatase at Week 24n=127 Participants	2.0	17.81
Aspartate amino transferase at Week 24n=127 Participants	0.5	12.88
Creatine kinase at Week 24n=126 Participants	0.6	82.86
Gamma glutamyl transferase at Week 24n=127 Participants	3.6	32.97
Lactate dehydrogenase at Week 24n=126 Participants	-1.2	25.99

Secondary/registry result/low confidence

Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), grams per liter	Standard deviation
PlaceboAlbumin at Week 24n=111 Participants	-0.5	2.37
Total protein at Week 24n=111 Participants	-0.8	3.52
SB-742457-15mgAlbumin at Week 24n=117 Participants	-0.5	2.44
Total protein at Week 24n=117 Participants	-0.9	4.00
SB-742457-35mgAlbumin at Week 24n=115 Participants	-0.6	2.54
Total protein at Week 24n=115 Participants	-1.3	3.50
DonepezilAlbumin at Week 24n=126 Participants	-0.8	2.62
Total protein at Week 24n=126 Participants	-1.2	3.62

Secondary/registry result/low confidence

Change From Baseline in Clinical Chemistry Parameter Blood Urea Nitrogen /Creatinine Ratio at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), Ratio	Standard deviation
Placebon=115 Participants	0.8	19.99
SB-742457-15mgn=121 Participants	2.3	19.32
SB-742457-35mgn=116 Participants	-3.7	17.44
Donepeziln=127 Participants	-0.3	17.76

Secondary/registry result/low confidence

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), mmol/L	Standard deviation
PlaceboCalcium at Week 24n=115 Participants	-0.008	0.0910
CO2 content/bicarbonate at Week 24n=115 Participants	0.5	2.91
Chloride at Week 24n=115 Participants	0.2	2.54
Glucose at Week 24n=115 Participants	0.02	1.108
HDL cholesterol at Week 24n=111 Participants	-0.023	0.2272
LDL cholesterol at Week 24n=107 Participants	0.149	0.8387
Magnesium at Week 24n=111 Participants	-0.001	0.0606
Phosphorus at Week 24n=111 Participants	0.010	0.1435
Potassium at Week 24n=115 Participants	-0.00	0.450
Sodium at Week 24n=115 Participants	0.1	2.24
Triglycerides at Week 24n=111 Participants	-0.040	0.8750
Urea/blood urea nitrogen at Week 24n=115 Participants	0.06	1.642
SB-742457-15mgCalcium at Week 24n=121 Participants	-0.012	0.0956
CO2 content/bicarbonate at Week 24n=121 Participants	0.3	2.46
Chloride at Week 24n=121 Participants	0.3	2.97
Glucose at Week 24n=121 Participants	0.03	1.327
HDL cholesterol at Week 24n=117 Participants	-0.060	0.2402
LDL cholesterol at Week 24n=116 Participants	-0.032	0.6176
Magnesium at Week 24n=117 Participants	-0.007	0.0538
Phosphorus at Week 24n=117 Participants	-0.018	0.1529
Potassium at Week 24n=121 Participants	0.09	0.458
Sodium at Week 24n=121 Participants	0.0	2.57
Triglycerides at Week 24n=117 Participants	-0.071	0.7146
Urea/blood urea nitrogen at Week 24n=121 Participants	0.29	1.510
SB-742457-35mgCalcium at Week 24n=116 Participants	-0.025	0.1215
CO2 content/bicarbonate at Week 24n=116 Participants	-0.5	3.01
Chloride at Week 24n=116 Participants	0.1	2.87
Glucose at Week 24n=116 Participants	0.14	1.808
HDL cholesterol at Week 24n=115 Participants	-0.060	0.3050
LDL cholesterol at Week 24n=113 Participants	-0.115	0.5971
Magnesium at Week 24n=115 Participants	-0.002	0.0569
Phosphorus at Week 24n=115 Participants	0.043	0.1728
Potassium at Week 24n=116 Participants	0.04	0.440
Sodium at Week 24n=116 Participants	-0.2	2.43
Triglycerides at Week 24n=115 Participants	-0.024	0.7678
Urea/blood urea nitrogen at Week 24n=116 Participants	0.14	1.467
DonepezilCalcium at Week 24n=127 Participants	-0.013	0.0932
CO2 content/bicarbonate at Week 24n=127 Participants	0.5	2.84
Chloride at Week 24n=127 Participants	-0.0	2.70
Glucose at Week 24n=127 Participants	0.07	1.605
HDL cholesterol at Week 24n=126 Participants	-0.035	0.2477
LDL cholesterol at Week 24n=122 Participants	-0.032	0.7417
Magnesium at Week 24n=126 Participants	-0.001	0.0591
Phosphorus at Week 24n=126 Participants	0.026	0.1752
Potassium at Week 24n=127 Participants	0.05	0.450
Sodium at Week 24n=127 Participants	0.4	2.31
Triglycerides at Week 24n=126 Participants	0.082	1.0874
Urea/blood urea nitrogen at Week 24n=127 Participants	0.10	1.453

Secondary/registry result/low confidence

Change From Baseline in Clinical Chemistry Parameters Creatinine, Direct Bilirubin and Total Bilirubin at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), umol/L	Standard deviation
PlaceboCreatinine at Week 24n=115 Participants	-0.3	20.40
Direct bilirubin at Week 24n=115 Participants	-0.1	0.79
Total bilirubin at Week 24n=115 Participants	-0.1	3.33
SB-742457-15mgCreatinine at Week 24n=121 Participants	1.2	10.83
Direct bilirubin at Week 24n=121 Participants	0.1	0.84
Total bilirubin at Week 24n=121 Participants	-0.1	2.82
SB-742457-35mgCreatinine at Week 24n=116 Participants	5.7	10.64
Direct bilirubin at Week 24n=116 Participants	-0.1	1.17
Total bilirubin at Week 24n=116 Participants	0.0	3.66
DonepezilCreatinine at Week 24n=127 Participants	1.4	8.53
Direct bilirubin at Week 24n=127 Participants	-0.1	1.01
Total bilirubin at Week 24n=127 Participants	-0.8	3.89

Secondary/registry result/low confidence

Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), giga cells per liter	Standard deviation
PlaceboBasophils at Week 24n=117 Participants	0.001	0.0168
Eosinophils at Week 24n=117 Participants	-0.011	0.0923
Lymphocytes at Week 24n=117 Participants	-0.037	0.4182
Monocytes at Week 24n=117 Participants	-0.002	0.1415
Platelet count at Week 24n=117 Participants	-4.8	33.13
Segmented neutrophils at Week 24n=117 Participants	0.002	1.2619
Total neutrophils at Week 24n=117 Participants	0.002	1.2619
White blood cell count at Week 24n=117 Participants	-0.05	1.357
SB-742457-15mgBasophils at Week 24n=121 Participants	0.002	0.0189
Eosinophils at Week 24n=121 Participants	-0.006	0.0858
Lymphocytes at Week 24n=121 Participants	-0.075	0.4373
Monocytes at Week 24n=121 Participants	-0.007	0.1403
Platelet count at Week 24n=119 Participants	-8.7	32.33
Segmented neutrophils at Week 24n=121 Participants	0.015	1.3909
Total neutrophils at Week 24n=121 Participants	0.015	1.3909
White blood cell count at Week 24n=121 Participants	-0.08	1.551
SB-742457-35mgBasophils at Week 24n=115 Participants	0.003	0.0183
Eosinophils at Week 24n=115 Participants	-0.004	0.1272
Lymphocytes at Week 24n=115 Participants	-0.151	0.3949
Monocytes at Week 24n=115 Participants	0.000	0.1643
Platelet count at Week 24n=115 Participants	-5.3	36.83
Segmented neutrophils at Week 24n=115 Participants	0.163	1.2329
Total neutrophils at Week 24n=115 Participants	0.163	1.2329
White blood cell count at Week 24n=115 Participants	0.01	1.295
DonepezilBasophils at Week 24n=124 Participants	-0.001	0.0173
Eosinophils at Week 24n=124 Participants	-0.004	0.0997
Lymphocytes at Week 24n=124 Participants	-0.047	0.5084
Monocytes at Week 24n=124 Participants	-0.008	0.1306
Platelet count at Week 24n=123 Participants	-9.4	36.13
Segmented neutrophils at Week 24n=124 Participants	-0.109	1.1543
Total neutrophils at Week 24n=124 Participants	-0.110	1.1550
White blood cell count at Week 24n=124 Participants	-0.17	1.288

Secondary/registry result/low confidence

Change From Baseline in Hematology Parameter Hematocrit

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), Ratio	Standard deviation
Placebon=118 Participants	0.0038	0.02264
SB-742457-15mgn=122 Participants	0.0037	0.02242
SB-742457-35mgn=116 Participants	-0.0003	0.02509
Donepeziln=124 Participants	0.0002	0.02351

Secondary/registry result/low confidence

Change From Baseline in Hematology Parameters Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), grams per liter	Standard deviation
PlaceboHemoglobin at Week 24n=118 Participants	-1.1	7.24
Mean corpuscle hemoglobin concentration at Week 24n=114 Participants	-5.3	8.99
SB-742457-15mgHemoglobin at Week 24n=122 Participants	-1.6	7.40
Mean corpuscle hemoglobin concentration at Week 24n=117 Participants	-5.9	9.74
SB-742457-35mgHemoglobin at Week 24n=116 Participants	-1.8	8.06
Mean corpuscle hemoglobin concentration at Week 24n=113 Participants	-3.9	9.73
DonepezilHemoglobin at Week 24n=124 Participants	-1.6	7.55
Mean corpuscle hemoglobin concentration at Week 24n=122 Participants	-4.2	9.64

Secondary/registry result/low confidence

Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), picograms	Standard deviation
Placebon=114 Participants	-0.21	0.949
SB-742457-15mgn=117 Participants	-0.19	1.173
SB-742457-35mgn=113 Participants	-0.10	1.023
Donepeziln=122 Participants	-0.08	0.830

Secondary/registry result/low confidence

Change From Baseline in Hematology Parameter Mean Corpuscle Volume and Mean Platelet Volume at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), femtoliters	Standard deviation
PlaceboMean corpuscle volume at Week 24n=118 Participants	0.8	2.84
Mean platelet volume at Week 24n=145 Participants	-0.01	0.711
SB-742457-15mgMean corpuscle volume at Week 24n=122 Participants	1.4	2.45
Mean platelet volume at Week 24n=145 Participants	-0.04	0.626
SB-742457-35mgMean corpuscle volume at Week 24n=116 Participants	0.6	2.35
Mean platelet volume at Week 24n=133 Participants	0.13	0.715
DonepezilMean corpuscle volume at Week 24n=124 Participants	0.9	2.43
Mean platelet volume at Week 24n=151 Participants	0.03	0.627

Secondary/registry result/low confidence

Change From Baseline in Hematology Parameter Red Blood Cell Count at Week 24

Time frame:Baseline (Week 0) and Week 24

change from baseline, improvement

Posted result

Group	Value (mean), trillion cells per liter	Standard deviation
Placebon=114 Participants	-0.03	0.276
SB-742457-15mgn=117 Participants	0.01	0.256
SB-742457-35mgn=113 Participants	-0.08	0.329
Donepeziln=122 Participants	-0.07	0.262

Publications (1)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Maher-Edwards G, Watson C, Ascher J, Barnett C, Boswell D, Davies J, Fernandez M, Kurz A, Zanetti O, Safirstein B, Schronen JP, Zvartau-Hind M, Gold M. Two randomized controlled trials of SB742457 in mild-to-moderate Alzheimer's disease. Alzheimers Dement (N Y). 2015 May 7;1(1):23-36. doi: 10.1016/j.trci.2015.04.001. eCollection 2015 Jun.
PMID29854923via DERIVED

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.