CompletedPhase 2Results posted

A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease

Study AZ3110866, a Fixed Dose Study of SB-742457 Versus Placebo When Added to Existing Donepezil Treatment in Subjects With Mild-to-moderate Alzheimer's Disease

Lead sponsor

GlaxoSmithKline

Assets

Donepezil / Intepirdine

Listed sites

102

Recruiting sites

Enrollment

682

actual

Study population

Alzheimer’s disease

Key I/E criteria

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

Primary endpoints

•ADAS-Cog•Clinical Dementia Rating-Sum of Boxes (CDR-SB)

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 IDAZ3110866

NCT IDNCT00710684

Timeline

Milestones

Study start2008-07-01actual

Study first posted2008-07-04estimated

Primary completion2010-05-21actual

Study completion2010-11-16actual

Last update posted2017-12-07actual

Results first posted2017-12-07actual

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 no evidence of disorders that are thought to be the cause of, or contributing to the severity of the subject's dementia and a documented history of at least 6 months of ongoing donepezil therapy with stable dosing for at least the last 2 months.

•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 abstinence or an approved form of birth control.

•Subjects must have adequate blood pressure and laboratory values

Exclusion criteria

•Subjects with a diagnosis of possible, probable or definite vascular dementia may not participate.

•Subjects with known hypersensitivity to sunlight or a history of seizures, 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 (34)

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

Function / daily living

Global cognition

20 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/protocol endpoint

Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24

Time frame:Baseline(Week 0) and Week 24

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

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
Donepezil + Placebon=193 Participants	1.2	0.45
Donepezil + SB-742457 15 mgn=184 Participants	0.5	0.44
Donepezil + SB-742457 35 mgn=200 Participants	-0.4	0.41

Mean Difference (Net)-0.795% CI-1.9 - 0.5p0.279mixed model for repeated measures (MMRM)

SB-742457 15mg versus placebo at Week 24

Mean Difference (Net)-1.595% CI-2.7 - -0.3p0.012MMRM

SB-742457 35mg versus placebo at Week 24

Primary/registry result

Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24

Time frame:Baseline(Week 0) and Week 24

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Donepezil + Placebon=191 Participants	0.9	0.13
Donepezil + SB-742457 15 mgn=184 Participants	0.8	0.13
Donepezil + SB-742457 35 mgn=200 Participants	0.7	0.11

Mean Difference (Net)-0.195% CI-0.4 - 0.3p0.711MMRM

SB-742457 15 mg versus placebo at Week 24

Mean Difference (Net)-0.195% CI-0.5 - 0.2p0.462MMRM

SB-742457 35 mg versus placebo 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

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48

Time frame:Baseline (Week 0) and Week 12, 36 and 48

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in CDR-SB Score at Week 12, 36 and 48

Time frame:Baseline (Week 0) and Week 12, 36, 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in RBANS Score at Week 12, 36 and 48

Time frame:Baseline (Week 0) and Week 12, 36 and 48

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48

Time frame:Baseline (Week 0) and Week 24 and 48

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene

Time frame:Baseline (Week 0) to Week 24 and Week 48

ADAS-Cog

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene

Time frame:Baseline (Week 0) to Week 24 and Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in RBANS Scale in Participants With APOE4 Gene

Time frame:Baseline (Week 0) to Week 24 and Week 48

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

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Donepezil + Placebon=190 Participants	-3.6	1.18
Donepezil + SB-742457 15 mgn=176 Participants	-5.9	1.29
Donepezil + SB-742457 35 mgn=193 Participants	-4.0	1.09

Mean Difference (Net)-2.495% CI-5.8 - 1.1p0.174MMRM

SB-742457 15 mg versus placebo at Week 24

Mean Difference (Net)-0.595% CI-3.6 - 2.7p0.776MMRM

SB-742457 35 mg versus placebo at Week 24

Secondary/registry result

Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48

Time frame:Baseline (Week 0) and Week 12, 36 and 48

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Donepezil + PlaceboWeek 12n=206 Participants	0.4	0.33
Week 36n=164 Participants	2.1	0.45
Week 48n=145 Participants	3.4	0.52
Donepezil + SB-742457 15 mgWeek 12n=202 Participants	0.1	0.37
Week 36n=156 Participants	2.1	0.48
Week 48n=142 Participants	3.4	0.60
Donepezil + SB-742457 35 mgWeek 12n=219 Participants	-0.9	0.34
Week 36n=181 Participants	0.9	0.45
Week 48n=170 Participants	1.8	0.50

Mean Difference (Net)-0.295% CI-1.2 - 0.7p0.631MMRM

SB-742457 15 mg versus placebo at Week 12

Mean Difference (Net)-1.395% CI-2.2 - -0.4p0.006MMRM

SB-742457 35 mg versus placebo at Week 12

Mean Difference (Net)0.095% CI-1.3 - 1.2p0.947MMRM

SB-742457 15 mg versus placebo at Week 36

Mean Difference (Net)-1.295% CI-2.5 - 0.0p0.057MMRM

SB-742457 35 mg versus placebo at Week 36

Mean Difference (Net)-0.195% CI-1.6 - 1.5p0.925MMRM

SB-742457 15 mg versus placebo at Week 48

Mean Difference (Net)-1.695% CI-3.1 - -0.2p0.024MMRM

SB-742457 35 mg versus placebo at Week 48

Secondary/registry result

Change From Baseline in CDR-SB Score at Week 12, 36 and 48

Time frame:Baseline (Week 0) and Week 12, 36, 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Donepezil + PlaceboWeek 12n=203 Participants	0.5	0.10
Week 36n=163 Participants	1.2	0.15
Week 48n=146 Participants	1.6	0.16
Donepezil + SB-742457 15 mgWeek 12n=199 Participants	0.4	0.09
Week 36n=154 Participants	1.4	0.18
Week 48n=142 Participants	1.9	0.20
Donepezil + SB-742457 35 mgWeek 12n=221 Participants	0.2	0.08
Week 36n=179 Participants	1.0	0.13
Week 48n=170 Participants	1.5	0.16

Mean Difference (Net)-0.195% CI-0.4 - 0.1p0.387MMRM

SB-742457 15 mg versus placebo at Week 12

Mean Difference (Net)-0.395% CI-0.5 - -0.1p0.018MMRM

SB-742457 35 mg versus placebo at Week 12

Mean Difference (Net)0.295% CI-0.3 - 0.6p0.439MMRM

SB-742457 15 mg versus placebo at Week 36

Mean Difference (Net)-0.295% CI-0.6 - 0.2p0.336MMRM

SB-742457 35 mg versus placebo at Week 36

Mean Difference (Net)0.395% CI-0.2 - 0.8p0.190MMRM

SB-742457 15 mg versus placebo at Week 48

Mean Difference (Net)-0.195% CI-0.5 - 0.4p0.787MMRM

SB-742457 35 mg versus placebo at Week 48

Secondary/registry result

Change From Baseline in RBANS Score at Week 12, 36 and 48

Time frame:Baseline (Week 0) and Week 12, 36 and 48

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Donepezil + PlaceboWeek 12n=200 Participants	-7.2	0.94
Week 36n=161 Participants	-3.9	1.32
Week 48n=143 Participants	-7.3	1.36
Donepezil + SB-742457 15 mgWeek 12n=194 Participants	-8.5	1.02
Week 36n=153 Participants	-4.8	1.21
Week 48n=136 Participants	-9.4	1.45
Donepezil + SB-742457 35 mgWeek 12n=214 Participants	-6.5	0.79
Week 36n=174 Participants	-1.8	1.19
Week 48n=164 Participants	-4.7	1.25

Mean Difference (Net)-1.395% CI-4.0 - 1.4p0.337MMRM

SB-742457 15 mg versus placebo at Week 12

Mean Difference (Net)0.695% CI-1.7 - 3.0p0.596MMRM

SB-742457 35 mg versus placebo at Week 12

Mean Difference (Net)-0.995% CI-4.4 - 2.7p0.634MMRM

SB-742457 15 mg versus placebo at Week 36

Mean Difference (Net)2.195% CI-1.4 - 5.6p0.238MMRM

SB-742457 35 mg versus placebo at Week 36

Mean Difference (Net)-2.195% CI-6.0 - 1.8p0.292MMRM

SB-742457 15 mg versus placebo at Week 48

Mean Difference (Net)2.695% CI-1.0 - 6.2p0.161MMRM

SB-742457 35 mg versus placebo at Week 48

Secondary/registry result

Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48

Time frame:Baseline (Week 0) and Week 24 and 48

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Donepezil + PlaceboWeek 24n=196 Participants	-0.4	0.21
Week 48n=149 Participants	-1.1	0.28
Donepezil + SB-742457 15 mgWeek 24n=188 Participants	-0.3	0.23
Week 48n=145 Participants	-1.3	0.33
Donepezil + SB-742457 35 mgWeek 24n=209 Participants	0.1	0.21
Week 48n=172 Participants	-0.7	0.27

Mean Difference (Net)0.095% CI-0.6 - 0.6p0.962MMRM

SB-742457 15 mg versus placebo at Week 24

Mean Difference (Net)0.495% CI-0.1 - 1.0p0.134MMRM

SB-742457 35 mg versus placebo at Week 24

Mean Difference (Net)-0.195% CI-1.0 - 0.7p0.782MMRM

SB-742457 15 mg versus placebo at Week 48

Mean Difference (Net)0.495% CI-0.3 - 1.2p0.268MMRM

SB-742457 35 mg versus placebo at Week 48

Secondary/registry result

Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene

Time frame:Baseline (Week 0) to Week 24 and Week 48

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (mean), Score on scale	Standard deviation
Donepezil + PlaceboWeek 24n=98 Participants	1.9	5.58
Week 48n=74 Participants	4.7	6.52
Donepezil + SB-742457 15 mgWeek 24n=94 Participants	1.0	6.63
Week 48n=72 Participants	4.2	7.46
Donepezil + SB-742457 35 mgWeek 24n=114 Participants	-0.1	5.40
Week 48n=90 Participants	1.8	5.72

Secondary/registry result

Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene

Time frame:Baseline (Week 0) to Week 24 and Week 48

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (mean), Score on scale	Standard deviation
Donepezil + PlaceboWeek 24n=95 Participants	1.1	2.02
Week 48n=75 Participants	1.8	1.98
Donepezil + SB-742457 15 mgWeek 24n=94 Participants	0.6	1.59
Week 48n=71 Participants	1.5	2.11
Donepezil + SB-742457 35 mgWeek 24n=113 Participants	0.8	1.47
Week 48n=91 Participants	1.4	1.92

Secondary/registry result

Change From Baseline in RBANS Scale in Participants With APOE4 Gene

Time frame:Baseline (Week 0) to Week 24 and Week 48

change from baseline, improvement

Posted result

Group	Value (mean), Score on scale	Standard deviation
Donepezil + PlaceboWeek 24n=96 Participants	-5.2	14.30
Week 48n=74 Participants	-7.7	16.46
Donepezil + SB-742457 15 mgWeek 24n=94 Participants	-6.0	20.07
Week 48n=72 Participants	-11.3	16.13
Donepezil + SB-742457 35 mgWeek 24n=110 Participants	-6.0	14.84
Week 48n=87 Participants	-5.9	14.04

Function / daily living

2 endpoints

Secondary/protocol endpoint

Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48

Time frame:Baseline (Week 0) and Week 12, 24, 36 and 48

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48

Time frame:Baseline (Week 0) and Week 12, 24, 36 and 48

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Score on scale	Standard error
Donepezil + PlaceboWeek 12n=202 Participants	-1.4	0.57
Week 24n=192 Participants	-3.4	0.66
Week 36n=164 Participants	-3.7	0.67
Week 48n=147 Participants	-5.5	0.85
Donepezil + SB-742457 15 mgWeek 12n=200 Participants	-0.8	0.49
Week 24n=185 Participants	-1.9	0.61
Week 36n=159 Participants	-3.8	0.80
Week 48n=144 Participants	-5.0	0.87
Donepezil + SB-742457 35 mgWeek 12n=222 Participants	0.3	0.47
Week 24n=209 Participants	-1.4	0.60
Week 36n=183 Participants	-1.8	0.65
Week 48n=171 Participants	-3.5	0.76

Mean Difference (Net)0.695% CI-0.8 - 2.1p0.396MMRM

SB-742457 15 mg versus placebo at Week 12

Mean Difference (Net)1.795% CI0.3 - 3.2p0.019MMRM

SB-742457 35 mg versus placebo at Week 12

Mean Difference (Net)1.495% CI-0.3 - 3.2p0.110MMRM

SB-742457 15 mg versus placebo at Week 24

Mean Difference (Net)2.095% CI0.3 - 3.7p0.024MMRM

SB-742457 35 mg versus placebo at Week 24

Mean Difference (Net)-0.195% CI-2.1 - 2.0p0.944MMRM

SB-742457 15 mg versus placebo ate Week 36

Mean Difference (Net)1.995% CI0.1 - 3.8p0.037MMRM

SB-742457 35 mg versus placebo at Week 36

Mean Difference (Net)0.595% CI-1.9 - 2.9p0.705MMRM

SB-742457 15 mg versus placebo at Week 48

Mean Difference (Net)1.995% CI-0.3 - 4.2p0.088MMRM

SB-742457 35 mg versus placebo at Week 48

Safety / tolerability / PK

4 endpoints

Secondary/protocol endpoint

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase

Time frame:Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal)

event count, event

Secondary/protocol endpoint

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

Time frame:Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

concentration, descriptive

Secondary/registry result

Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase

Time frame:Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal)

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Donepezil + PlaceboAny AEn=225 Participants	125	-
Any SAEn=225 Participants	17	-
Donepezil + SB-742457 15 mgAny AEn=221 Participants	137	-
Any SAEn=221 Participants	26	-
Donepezil + SB-742457 35 mgAny AEn=236 Participants	146	-
Any SAEn=236 Participants	27	-

Secondary/registry result

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

Time frame:Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

concentration, descriptive

Posted result

Group	Value (geometric_mean), Nanogram hour per milliliter (ng*h/mL)	Geometric coefficient of variation
Donepezil + SB-742457 15 mgn=215 Participants	1640.76	35.96
Donepezil + SB-742457 35 mgn=233 Participants	4160.29	31.67

Other (unclassified)

8 endpoints

Secondary/protocol endpoint/low confidence

Number of Participants With Parameters of Clinical Concern - Hematology

Time frame:Up to Week 48

event count, event

Secondary/protocol endpoint/low confidence

Number of Participants With Parameters of Clinical Concern - Clinical Chemistry

Time frame:Up to Week 48

event count, event

Secondary/protocol endpoint/low confidence

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

Time frame:Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

concentration, descriptive

Secondary/protocol endpoint/low confidence

Exposure Estimates for Donepezil (Cavgss)

Time frame:Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

descriptive

Secondary/registry result/low confidence

Number of Participants With Parameters of Clinical Concern - Hematology

Time frame:Up to Week 48

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Donepezil + PlaceboEosinophils, highn=222 Participants	1	-
Hematocrit, lown=222 Participants	2	-
Hematocrit, highn=222 Participants	0	-
Hemoglobin, lown=222 Participants	5	-
Hemoglobin, highn=222 Participants	3	-
Lymphocytes, lown=222 Participants	6	-
Lymphocytes, highn=222 Participants	0	-
MCH, lown=204 Participants	0	-
MCV, lown=222 Participants	0	-
Monocytes, lown=222 Participants	35	-
Monocytes, highn=222 Participants	0	-
Neutrophil bands, highn=1 Participants	0	-
Platelet count, lown=222 Participants	1	-
Platelet count, highn=222 Participants	2	-
Segmented Neutrophils, lown=222 Participants	7	-
Segmented Neutrophils, highn=222 Participants	3	-
Total Neutrophils, lown=222 Participants	7	-
Total Neutrophils, highn=222 Participants	0	-
WBC, lown=222 Participants	4	-
WBC, highn=222 Participants	0	-
Donepezil + SB-742457 15 mgEosinophils, highn=217 Participants	0	-
Hematocrit, lown=217 Participants	2	-
Hematocrit, highn=217 Participants	1	-
Hemoglobin, lown=217 Participants	3	-
Hemoglobin, highn=217 Participants	1	-
Lymphocytes, lown=217 Participants	5	-
Lymphocytes, highn=217 Participants	2	-
MCH, lown=198 Participants	1	-
MCV, lown=217 Participants	1	-
Monocytes, lown=217 Participants	32	-
Monocytes, highn=217 Participants	1	-
Neutrophil bands, highn=3 Participants	1	-
Platelet count, lown=216 Participants	4	-
Platelet count, highn=216 Participants	3	-
Segmented Neutrophils, lown=217 Participants	3	-
Segmented Neutrophils, highn=217 Participants	4	-
Total Neutrophils, lown=217 Participants	3	-
Total Neutrophils, highn=217 Participants	3	-
WBC, lown=217 Participants	1	-
WBC, highn=217 Participants	3	-
Donepezil + SB-742457 35 mgEosinophils, highn=235 Participants	4	-
Hematocrit, lown=235 Participants	1	-
Hematocrit, highn=235 Participants	0	-
Hemoglobin, lown=235 Participants	8	-
Hemoglobin, highn=235 Participants	0	-
Lymphocytes, lown=235 Participants	7	-
Lymphocytes, highn=235 Participants	1	-
MCH, lown=216 Participants	0	-
MCV, lown=235 Participants	0	-
Monocytes, lown=235 Participants	32	-
Monocytes, highn=235 Participants	0	-
Neutrophil bands, highn=3 Participants	1	-
Platelet count, lown=235 Participants	3	-
Platelet count, highn=235 Participants	5	-
Segmented Neutrophils, lown=235 Participants	7	-
Segmented Neutrophils, highn=235 Participants	5	-
Total Neutrophils, lown=235 Participants	7	-
Total Neutrophils, highn=235 Participants	2	-
WBC, lown=235 Participants	5	-
WBC, highn=235 Participants	2	-

Secondary/registry result/low confidence

Number of Participants With Parameters of Clinical Concern - Clinical Chemistry

Time frame:Up to Week 48

event count, event

Posted result

Group	Value (count_of_participants), Participants	Reported bounds
Donepezil + PlaceboALT, highn=222 Participants	2	-
Alkaline Phosphatase, highn=222 Participants	5	-
ASAT, highn=222 Participants	2	-
BUN/Creatinine ratio, highn=222 Participants	11	-
Calcium, lown=222 Participants	0	-
Carbon dioxide content/Bicarbonate, lown=222 Participants	3	-
Cholesterol, highn=204 Participants	11	-
Creatine Kinase, highn=204 Participants	5	-
Creatinine, highn=222 Participants	3	-
Direct Bilirubin, highn=222 Participants	2	-
GGT, highn=222 Participants	5	-
Glucose, lown=222 Participants	17	-
Glucose, highn=222 Participants	54	-
HDL Cholesterol, direct, lown=204 Participants	3	-
LDL Cholesterol, highn=201 Participants	35	-
Magnesium, lown=204 Participants	0	-
Phosphorus, inorganic, highn=204 Participants	0	-
Potassium, highn=222 Participants	2	-
Sodium, highn=222 Participants	0	-
Total Bilirubin, highn=222 Participants	2	-
Triglycerides, highn=204 Participants	1	-
Urea/BUN, highn=222 Participants	17	-
Donepezil + SB-742457 15 mgALT, highn=217 Participants	4	-
Alkaline Phosphatase, highn=217 Participants	6	-
ASAT, highn=217 Participants	7	-
BUN/Creatinine ratio, highn=217 Participants	7	-
Calcium, lown=217 Participants	0	-
Carbon dioxide content/Bicarbonate, lown=217 Participants	2	-
Cholesterol, highn=196 Participants	4	-
Creatine Kinase, highn=196 Participants	2	-
Creatinine, highn=217 Participants	3	-
Direct Bilirubin, highn=217 Participants	1	-
GGT, highn=217 Participants	7	-
Glucose, lown=217 Participants	24	-
Glucose, highn=217 Participants	42	-
HDL Cholesterol, direct, lown=195 Participants	0	-
LDL Cholesterol, highn=195 Participants	29	-
Magnesium, lown=195 Participants	1	-
Phosphorus, inorganic, highn=196 Participants	0	-
Potassium, highn=217 Participants	10	-
Sodium, highn=217 Participants	1	-
Total Bilirubin, highn=217 Participants	1	-
Triglycerides, highn=196 Participants	0	-
Urea/BUN, highn=217 Participants	12	-
Donepezil + SB-742457 35 mgALT, highn=235 Participants	4	-
Alkaline Phosphatase, highn=235 Participants	4	-
ASAT, highn=235 Participants	4	-
BUN/Creatinine ratio, highn=235 Participants	5	-
Calcium, lown=235 Participants	1	-
Carbon dioxide content/Bicarbonate, lown=235 Participants	2	-
Cholesterol, highn=215 Participants	7	-
Creatine Kinase, highn=215 Participants	6	-
Creatinine, highn=235 Participants	5	-
Direct Bilirubin, highn=235 Participants	1	-
GGT, highn=235 Participants	7	-
Glucose, lown=235 Participants	13	-
Glucose, highn=235 Participants	54	-
HDL Cholesterol, direct, lown=215 Participants	2	-
LDL Cholesterol, highn=214 Participants	40	-
Magnesium, lown=215 Participants	0	-
Phosphorus, inorganic, highn=215 Participants	1	-
Potassium, highn=235 Participants	9	-
Sodium, highn=235 Participants	1	-
Total Bilirubin, highn=235 Participants	1	-
Triglycerides, highn=215 Participants	0	-
Urea/BUN, highn=235 Participants	25	-

Secondary/registry result/low confidence

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

Time frame:Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

concentration, descriptive

Posted result

Group	Value (geometric_mean), ng/mL	Geometric coefficient of variation
Donepezil + SB-742457 15 mgn=215 Participants	53.42	38.58
Donepezil + SB-742457 35 mgn=233 Participants	135.05	33.08

Secondary/registry result/low confidence

Exposure Estimates for Donepezil (Cavgss)

Time frame:Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

descriptive

Posted result

Group	Value (geometric_mean), ng/mL	Geometric coefficient of variation
Donepezil 5 mgn=179 Participants	20.72	45.07
Donepezil 7.5 mgn=1 Participants	17.68	NA
Donepezil 10 mgn=484 Participants	39.79	46.62
Donepezil 15 mgn=1 Participants	36.60	NA

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.