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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00710684
• Collaborator: (none)
• Enrollment: 682
• Locations: 102
• Arms: 3
• Actual Duration (Months): 28.5
• Patients Per Site: 6.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The study is designed to investigate the safety and efficacy of SB-742457 when added to stable donepezil treatment in subjects with mild-to-moderate Alzheimer's disease.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer's Disease	Drug: SB-742457 15mg; Drug: SB-742457 35mg; Drug: Placebo; Drug: donepezil 5-10mg	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 682 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: Jul 1, 2008
• Actual Primary Completion Date: May 21, 2010
• Actual Study Completion Date: Nov 16, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: DONEPEZIL + SB-742457 15 MG SB-742457 - 15mg added to existing donepezil treatment	Drug: SB-742457 15mg; SB-742457 - 15mg added to existing donepezil treatment; Drug: donepezil 5-10mg; existing donepezil treatment
Placebo Comparator: DONEPEZIL + PLACEBO Placebo added to existing donepezil	Drug: Placebo; Placebo added to existing donepezil; Drug: donepezil 5-10mg; existing donepezil treatment
Experimental: DONEPEZIL + SB-742457 35 MG SB-742457 - 35mg added to existing donepezil	Drug: SB-742457 35mg; SB-742457 - 35mg added to existing donepezil; Drug: donepezil 5-10mg; existing donepezil treatment

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24 [Baseline(Week 0) and Week 24]

   ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the case report form (CRF) for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean is presented.

2. Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24 [Baseline(Week 0) and Week 24]

   The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

Secondary Outcome Measures

1. Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24 [Baseline (Week 0) and Week 24]

   RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

2. Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48 [Baseline (Week 0) and Week 12, 36 and 48]

   ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the CRF for questions 3 to 6 and 8 to 11. In cases where more than one question was missing, a total score was not be imputed. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been present

3. Change From Baseline in CDR-SB Score at Week 12, 36 and 48 [Baseline (Week 0) and Week 12, 36, 48]

   The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

4. Change From Baseline in RBANS Score at Week 12, 36 and 48 [Baseline (Week 0) and Week 12, 36 and 48]

   RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

5. 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 [Baseline (Week 0) and Week 12, 24, 36 and 48]

   The ADCS-ADL is an interviewer-administered informant-based scale where the informant (caregiver) responds to 23 activities of daily living questions about the participant. The questions ranged from basic to instrumental activities of daily living and take approximately 20 minutes to complete. The Total score ranges from 0-78 and a higher score signified greater functional ability. The questionnaire was split into two types of questions, an initial question relating to whether a participant had completed a particular activity and then a follow on question which scored how much assistance the participant had required if they had performed that particular activity. The total score was calculated by adding up the responses for each of the individual activities. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

6. Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48 [Baseline (Week 0) and Week 24 and 48]

   The MMSE consisted of 11 items covering orientation, memory (recent and immediate), concentration, language and praxis. Scores ranged from 0 to 30, with lower scores indicating greater cognitive impairment. Scores for each of the 11 individual tests were not recorded on the CRF, therefore if any item was missing then the total score was be set to missing. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.

7. Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase [Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal)]

   An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

8. Number of Participants With Parameters of Clinical Concern - Hematology [Up to Week 48]

   Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Eosinophils (high-2), Hematocrit (low- 0.8, high-1.2), Lymphocytes (low-0.75, high-1.5), Mean Corpuscle Hemoglobin (MCH) (low-0.8, high-1.2), Monocytes(low-0.75, high-2), Neutrophil bands (high-10), Platelet count (low-100, high-500), Segmented Neutrophils (low-0.75, high-1.3), Total Neutrophils (low-0.75, high-1.5), and white blood cells (WBC) (low-3, high-15).

9. Number of Participants With Parameters of Clinical Concern - Clinical Chemistry [Up to Week 48]

   Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Alanine Amino Transferase (ALT) (high-1.5), Alkaline Phosphatase (high-1.5), Aspartate Amino Transferase (ASAT) (high-1.5), BUN/Creatinine ratio (high-1.5), Calcium (low- 0.75, high-1.25), Carbon dioxide content/Bicarbonate (low-15, high- 40), Cholesterol (high-1.25), Creatine Kinase ((low- 0.5, high-1.25), Creatinine (low- 0.5, high-1.25), Direct Bilirubin (high-1.5), Gamma Glutamyl Transferase (GGT) (high-2), Glucose (low- 3.6, high-7.8), HDL Cholesterol (low-0.65), LDL Cholesterol (hig-1.25), Magnesium (low-0.5, high-2), Phosphorus inorganic (low- 0.5, high-1.5), Potassium (low- 3, high-5.5), Sodium (low- 130, high-150), Total Bilirubin (high-1.5), Triglycerides (high -4) and Urea/BUN (high-11).

10. Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss) [Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48]

    AUCτss of SB-742457 was estimated via nonlinear mixed effect analysis. This pharmacokinetic(PK) model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.

11. Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss) [Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48]

    Cmin-ss was estimated via nonlinear mixed effect analysis. This PK model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.

12. Exposure Estimates for Donepezil (Cavgss) [Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48]

    Participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) were allowed to participate in this study. Cavgss for donepezil approximately 12 to 20 hours after dosing were summarized by donepezil dose level 5 mg/7.5 mg/10 mg/15 mg.

13. Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene [Baseline (Week 0) to Week 24 and Week 48]

    Genetic analyses was conducted to assess the effect of APOE4 carriage. ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five-point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores were recorded on the CRF for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.

14. Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene [Baseline (Week 0) to Week 24 and Week 48]

    Genetic analyses was conducted to assess the effect of APOE4 carriage. The CDR-SB is an interviewer administered scale and impairment is scored in following categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment was scored on a scale in which none =0, questionable =0.5, mild =1, moderate =2 and severe =3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher score indicating severe impairment. If there were any missing items then CDR-SB was set to missing and was not imputed. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.

15. Change From Baseline in RBANS Scale in Participants With APOE4 Gene [Baseline (Week 0) to Week 24 and Week 48]

    Genetic analyses was conducted to assess the effect of APOE4 carriage. RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 50 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Litchfield Park	Arizona	United States	85340
2	GSK Investigational Site	Fresno	California	United States	93720
3	GSK Investigational Site	Rancho Mirage	California	United States	92270
4	GSK Investigational Site	San Francisco	California	United States	94109
5	GSK Investigational Site	Hallandale Beach	Florida	United States	33009
6	GSK Investigational Site	Hialeah	Florida	United States	33016
7	GSK Investigational Site	Manchester	New Jersey	United States	08759
8	GSK Investigational Site	Syracuse	New York	United States	13210
9	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
10	GSK Investigational Site	Columbus	Ohio	United States	43210
11	GSK Investigational Site	Tulsa	Oklahoma	United States	74104
12	GSK Investigational Site	Memphis	Tennessee	United States	38119
13	GSK Investigational Site	Austin	Texas	United States	78757
14	GSK Investigational Site	Bennington	Vermont	United States	05201
15	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1022AAO
16	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires	Argentina	C1405BCH
17	GSK Investigational Site	Ciudad de Buenos Aires	Buenos Aires	Argentina	C1431FWO
18	GSK Investigational Site	La Plata	Buenos Aires	Argentina	B1900AVG
19	GSK Investigational Site	Cordoba	Córdova	Argentina	5000
20	GSK Investigational Site	Buenos Aires		Argentina	1425
21	GSK Investigational Site	Santa Fe		Argentina	3000
22	GSK Investigational Site	Kogarah	New South Wales	Australia	2217
23	GSK Investigational Site	Herston	Queensland	Australia	4029
24	GSK Investigational Site	Woodville	South Australia	Australia	5011
25	GSK Investigational Site	Ballarat	Victoria	Australia	3350
26	GSK Investigational Site	Heidelberg West	Victoria	Australia	3084
27	GSK Investigational Site	Kew	Victoria	Australia	3101
28	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
29	GSK Investigational Site	Saint John	New Brunswick	Canada	E2L 3L6
30	GSK Investigational Site	Kentville	Nova Scotia	Canada	B4N 4K9
31	GSK Investigational Site	Ottawa	Ontario	Canada	K1G 4G3
32	GSK Investigational Site	Peterborough	Ontario	Canada	K9H 2P4
33	GSK Investigational Site	Toronto	Ontario	Canada	M3B 2S7
34	GSK Investigational Site	Toronto	Ontario	Canada	M6M 3Z5
35	GSK Investigational Site	Greenfield Park	Quebec	Canada	J4V 2J2
36	GSK Investigational Site	Montreal	Quebec	Canada	H1T 2M4
37	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1H 1Z1
38	GSK Investigational Site	Sherbrooke	Quebec	Canada	J1J 3H5
39	GSK Investigational Site	Québec		Canada	G1R 3X5
40	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	7510186
41	GSK Investigational Site	Santiago	Región Metro De Santiago	Chile	7560356
42	GSK Investigational Site	Viña del Mar	Valparaíso	Chile	252-0997
43	GSK Investigational Site	Santiago		Chile
44	GSK Investigational Site	Melnik		Czechia	27601
45	GSK Investigational Site	Olomouc		Czechia	775 20
46	GSK Investigational Site	Ostrava		Czechia	702 00
47	GSK Investigational Site	Pardubice		Czechia	53203
48	GSK Investigational Site	Plzen		Czechia	301 00
49	GSK Investigational Site	Praha 10		Czechia	10000
50	GSK Investigational Site	Praha 1		Czechia	110 00
51	GSK Investigational Site	Praha 4		Czechia	14059
52	GSK Investigational Site	Ellwangen	Baden-Wuerttemberg	Germany	73479
53	GSK Investigational Site	Stuttgart	Baden-Wuerttemberg	Germany	70176
54	GSK Investigational Site	Tuebingen	Baden-Wuerttemberg	Germany	72076
55	GSK Investigational Site	Ulm	Baden-Wuerttemberg	Germany	89075
56	GSK Investigational Site	Alzenau	Bayern	Germany	63755
57	GSK Investigational Site	Guenzburg	Bayern	Germany	89312
58	GSK Investigational Site	Muenchen	Bayern	Germany	81675
59	GSK Investigational Site	Regensburg	Bayern	Germany	93053
60	GSK Investigational Site	Unterhaching	Bayern	Germany	82008
61	GSK Investigational Site	Bad Homburg	Hessen	Germany	61348
62	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern	Germany	19053
63	GSK Investigational Site	Schwerin	Mecklenburg-Vorpommern	Germany	19055
64	GSK Investigational Site	Achim	Niedersachsen	Germany	28832
65	GSK Investigational Site	Aachen	Nordrhein-Westfalen	Germany	52062
66	GSK Investigational Site	Bad Honnef	Nordrhein-Westfalen	Germany	53604
67	GSK Investigational Site	Bochum	Nordrhein-Westfalen	Germany	44869
68	GSK Investigational Site	Dresden	Sachsen	Germany	01097
69	GSK Investigational Site	Dresden	Sachsen	Germany	01309
70	GSK Investigational Site	Jena	Thueringen	Germany	07743
71	GSK Investigational Site	Berlin		Germany	10961
72	GSK Investigational Site	Berlin		Germany	12163
73	GSK Investigational Site	Berlin		Germany	13439
74	GSK Investigational Site	Chieti Scalo	Abruzzo	Italy	66013
75	GSK Investigational Site	Napoli	Campania	Italy	80131
76	GSK Investigational Site	San Felice A Cancello - Caserta	Campania	Italy	81027
77	GSK Investigational Site	Cassino (FR)	Lazio	Italy	03043
78	GSK Investigational Site	Roma	Lazio	Italy	00148
79	GSK Investigational Site	Roma	Lazio	Italy	00163
80	GSK Investigational Site	Brescia	Lombardia	Italy	25125
81	GSK Investigational Site	Castellanza (VA)	Lombardia	Italy	21053
82	GSK Investigational Site	Milano	Lombardia	Italy	20122
83	GSK Investigational Site	Milano	Lombardia	Italy	20132
84	GSK Investigational Site	Rho	Lombardia	Italy	20017
85	GSK Investigational Site	Torino	Piemonte	Italy	10126
86	GSK Investigational Site	Lido Di Camaiore (LU)	Toscana	Italy	55043
87	GSK Investigational Site	Pisa	Toscana	Italy	56126
88	GSK Investigational Site	Perugia	Umbria	Italy	06156
89	GSK Investigational Site	Valdagno (VI)	Veneto	Italy	36078
90	GSK Investigational Site	Verona	Veneto	Italy	37126
91	GSK Investigational Site	Baracaldo/Vizcaya		Spain	48903
92	GSK Investigational Site	Barcelona		Spain	08003
93	GSK Investigational Site	Barcelona		Spain	08014
94	GSK Investigational Site	Barcelona		Spain	08907
95	GSK Investigational Site	Burgos		Spain	09006
96	GSK Investigational Site	Castellón		Spain	12004
97	GSK Investigational Site	Madrid		Spain	28006
98	GSK Investigational Site	Murcia		Spain	30120
99	GSK Investigational Site	Salamanca		Spain	37007
100	GSK Investigational Site	San Sebastián		Spain	20014
101	GSK Investigational Site	San Vicente Del Raspeig/Alicante		Spain	03690
102	GSK Investigational Site	Valencia		Spain	46010

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00710684
• Other Study ID Numbers: AZ3110866
• First Posted: Jul 4, 2008
• Last Update Posted: Dec 7, 2017
• Last Verified: Nov 1, 2017

• Keywords provided by GlaxoSmithKline: Alzheimer's disease cognition SB-742457
• Additional relevant MeSH terms: Alzheimer Disease; Donepezil

Study Results

Participant Flow

Recruitment Details	A total of 684 participants were randomized from 100 centers i.e. Australia, Argentina, Chile, Canada, United States of America, Czech Republic, Spain, Italy, Germany between 01 July 2008 and 16 November 2010.
Pre-assignment Detail	Out of 1132 participants screened, 725 entered into 4-week placebo run-in period out of which 41 participants were placebo run-in failures. Out of 684 participants randomized, 682 were included in safety population (1 participant each from Donepezil+Placebo and Donepezil+SB742457 35 milligram [mg] group failed to take a dose of study medication).

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Period Title: Overall Study
STARTED	225	221	236
COMPLETED	151	147	172
NOT COMPLETED	74	74	64

Baseline Characteristics

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg	Total
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Total of all reporting groups
Overall Participants	223	218	236	677
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	73.1 (7.49)	74.2 (6.82)	73.8 (6.92)	73.7 (7.09)
Sex: Female, Male (Count of Participants)
Female	129 57.8%	118 54.1%	148 62.7%	395 58.3%
Male	94 42.2%	100 45.9%	88 37.3%	282 41.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	3 1.4%	2 0.8%	5 0.7%
White	223 100%	215 98.6%	233 98.7%	671 99.1%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 0.4%	1 0.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24
Description	ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the case report form (CRF) for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean is presented.
Time Frame	Baseline(Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	193	184	200
Least Squares Mean (Standard Error) [Score on scale]	1.2 (0.45)	0.5 (0.44)	-0.4 (0.41)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.279
	Comments
	Method	mixed model for repeated measures (MMRM)
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.7
	Confidence Interval	(2-Sided) 95%; -1.9 to 0.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.012
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.5
	Confidence Interval	(2-Sided) 95%; -2.7 to -0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24
Description	The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame	Baseline(Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	191	184	200
Least Squares Mean (Standard Error) [Score on scale]	0.9 (0.13)	0.8 (0.13)	0.7 (0.11)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.711
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.462
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24
Description	RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame	Baseline (Week 0) and Week 24

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available at the indicated time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	190	176	193
Least Squares Mean (Standard Error) [Score on scale]	-3.6 (1.18)	-5.9 (1.29)	-4.0 (1.09)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.174
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.4
	Confidence Interval	(2-Sided) 95%; -5.8 to 1.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.776
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -3.6 to 2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48
Description	ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicated greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores recorded on the CRF for questions 3 to 6 and 8 to 11. In cases where more than one question was missing, a total score was not be imputed. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been present
Time Frame	Baseline (Week 0) and Week 12, 36 and 48

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	223	218	236
Week 12	0.4 (0.33)	0.1 (0.37)	-0.9 (0.34)
Week 36	2.1 (0.45)	2.1 (0.48)	0.9 (0.45)
Week 48	3.4 (0.52)	3.4 (0.60)	1.8 (0.50)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.631
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -1.2 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.006
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -2.2 to -0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 36
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.947
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -1.3 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 36
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.057
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.5 to 0.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.925
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.6 to 1.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -3.1 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in CDR-SB Score at Week 12, 36 and 48
Description	The CDR-SB is an interviewer administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which none = 0, questionable = 0.5, mild = 1, moderate = 2 and severe = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18 (severe impairment). If there were any missing items then CDR-SB was set to missing and was not imputed. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame	Baseline (Week 0) and Week 12, 36, 48

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	223	218	236
Week 12	0.5 (0.10)	0.4 (0.09)	0.2 (0.08)
Week 36	1.2 (0.15)	1.4 (0.18)	1.0 (0.13)
Week 48	1.6 (0.16)	1.9 (0.20)	1.5 (0.16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.387
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.4 to 0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.018
	Comments
	Method	MMRM
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.5 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 36
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.439
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.2
	Confidence Interval	(2-Sided) 95%; -0.3 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 36
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.336
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.2
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.190
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.3
	Confidence Interval	(2-Sided) 95%; -0.2 to 0.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.787
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -0.5 to 0.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change From Baseline in RBANS Score at Week 12, 36 and 48
Description	RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame	Baseline (Week 0) and Week 12, 36 and 48

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	223	218	236
Week 12	-7.2 (0.94)	-8.5 (1.02)	-6.5 (0.79)
Week 36	-3.9 (1.32)	-4.8 (1.21)	-1.8 (1.19)
Week 48	-7.3 (1.36)	-9.4 (1.45)	-4.7 (1.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.337
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -4.0 to 1.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.596
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -1.7 to 3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 36
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.634
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.9
	Confidence Interval	(2-Sided) 95%; -4.4 to 2.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 36
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.238
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.1
	Confidence Interval	(2-Sided) 95%; -1.4 to 5.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg, Donepezil + SB-742457 35 mg
	Comments	SB-742457 15 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.292
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -6.0 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.161
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.6
	Confidence Interval	(2-Sided) 95%; -1.0 to 6.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	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
Description	The ADCS-ADL is an interviewer-administered informant-based scale where the informant (caregiver) responds to 23 activities of daily living questions about the participant. The questions ranged from basic to instrumental activities of daily living and take approximately 20 minutes to complete. The Total score ranges from 0-78 and a higher score signified greater functional ability. The questionnaire was split into two types of questions, an initial question relating to whether a participant had completed a particular activity and then a follow on question which scored how much assistance the participant had required if they had performed that particular activity. The total score was calculated by adding up the responses for each of the individual activities. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame	Baseline (Week 0) and Week 12, 24, 36 and 48

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	223	218	236
Week 12	-1.4 (0.57)	-0.8 (0.49)	0.3 (0.47)
Week 24	-3.4 (0.66)	-1.9 (0.61)	-1.4 (0.60)
Week 36	-3.7 (0.67)	-3.8 (0.80)	-1.8 (0.65)
Week 48	-5.5 (0.85)	-5.0 (0.87)	-3.5 (0.76)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.396
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -0.8 to 2.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 12
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.019
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.7
	Confidence Interval	(2-Sided) 95%; 0.3 to 3.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.110
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.4
	Confidence Interval	(2-Sided) 95%; -0.3 to 3.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.024
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.0
	Confidence Interval	(2-Sided) 95%; 0.3 to 3.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo ate Week 36
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.944
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -2.1 to 2.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 36
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; 0.1 to 3.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.705
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.5
	Confidence Interval	(2-Sided) 95%; -1.9 to 2.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.088
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; -0.3 to 4.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48
Description	The MMSE consisted of 11 items covering orientation, memory (recent and immediate), concentration, language and praxis. Scores ranged from 0 to 30, with lower scores indicating greater cognitive impairment. Scores for each of the 11 individual tests were not recorded on the CRF, therefore if any item was missing then the total score was be set to missing. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value. Baseline was Week 0 value. Data for adjusted mean has been presented.
Time Frame	Baseline (Week 0) and Week 24 and 48

Outcome Measure Data

Analysis Population Description

ITT population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	223	218	236
Week 24	-0.4 (0.21)	-0.3 (0.23)	0.1 (0.21)
Week 48	-1.1 (0.28)	-1.3 (0.33)	-0.7 (0.27)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.962
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.0
	Confidence Interval	(2-Sided) 95%; -0.6 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 24
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.134
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.1 to 1.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 15 mg
	Comments	SB-742457 15 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.782
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.1
	Confidence Interval	(2-Sided) 95%; -1.0 to 0.7
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Donepezil + Placebo, Donepezil + SB-742457 35 mg
	Comments	SB-742457 35 mg versus placebo at Week 48
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.268
	Comments
	Method	MMRM
	Comments	The MMRM model included fixed categorical terms for treatment, visit, treatment by visit interaction and country.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -0.3 to 1.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase
Description	An AE was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavorable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. An SAE was any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
Time Frame	Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal)

Outcome Measure Data

Analysis Population Description

Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	225	221	236
Any AE	125 56.1%	137 62.8%	146 61.9%
Any SAE	17 7.6%	26 11.9%	27 11.4%

10. Secondary Outcome

Title	Number of Participants With Parameters of Clinical Concern - Hematology
Description	Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Eosinophils (high-2), Hematocrit (low- 0.8, high-1.2), Lymphocytes (low-0.75, high-1.5), Mean Corpuscle Hemoglobin (MCH) (low-0.8, high-1.2), Monocytes(low-0.75, high-2), Neutrophil bands (high-10), Platelet count (low-100, high-500), Segmented Neutrophils (low-0.75, high-1.3), Total Neutrophils (low-0.75, high-1.5), and white blood cells (WBC) (low-3, high-15).
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	225	221	236
Eosinophils, high	1 0.4%	0 0%	4 1.7%
Hematocrit, low	2 0.9%	2 0.9%	1 0.4%
Hematocrit, high	0 0%	1 0.5%	0 0%
Hemoglobin, low	5 2.2%	3 1.4%	8 3.4%
Hemoglobin, high	3 1.3%	1 0.5%	0 0%
Lymphocytes, low	6 2.7%	5 2.3%	7 3%
Lymphocytes, high	0 0%	2 0.9%	1 0.4%
MCH, low	0 0%	1 0.5%	0 0%
MCV, low	0 0%	1 0.5%	0 0%
Monocytes, low	35 15.7%	32 14.7%	32 13.6%
Monocytes, high	0 0%	1 0.5%	0 0%
Neutrophil bands, high	0 0%	1 0.5%	1 0.4%
Platelet count, low	1 0.4%	4 1.8%	3 1.3%
Platelet count, high	2 0.9%	3 1.4%	5 2.1%
Segmented Neutrophils, low	7 3.1%	3 1.4%	7 3%
Segmented Neutrophils, high	3 1.3%	4 1.8%	5 2.1%
Total Neutrophils, low	7 3.1%	3 1.4%	7 3%
Total Neutrophils, high	0 0%	3 1.4%	2 0.8%
WBC, low	4 1.8%	1 0.5%	5 2.1%
WBC, high	0 0%	3 1.4%	2 0.8%

11. Secondary Outcome

Title	Number of Participants With Parameters of Clinical Concern - Clinical Chemistry
Description	Only parameters with values have been presented. Data has been reported for number of participants with high and/ or low values for Alanine Amino Transferase (ALT) (high-1.5), Alkaline Phosphatase (high-1.5), Aspartate Amino Transferase (ASAT) (high-1.5), BUN/Creatinine ratio (high-1.5), Calcium (low- 0.75, high-1.25), Carbon dioxide content/Bicarbonate (low-15, high- 40), Cholesterol (high-1.25), Creatine Kinase ((low- 0.5, high-1.25), Creatinine (low- 0.5, high-1.25), Direct Bilirubin (high-1.5), Gamma Glutamyl Transferase (GGT) (high-2), Glucose (low- 3.6, high-7.8), HDL Cholesterol (low-0.65), LDL Cholesterol (hig-1.25), Magnesium (low-0.5, high-2), Phosphorus inorganic (low- 0.5, high-1.5), Potassium (low- 3, high-5.5), Sodium (low- 130, high-150), Total Bilirubin (high-1.5), Triglycerides (high -4) and Urea/BUN (high-11).
Time Frame	Up to Week 48

Outcome Measure Data

Analysis Population Description

Safety population. Only those participants with data available at the specified time points were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	225	221	236
ALT, high	2 0.9%	4 1.8%	4 1.7%
Alkaline Phosphatase, high	5 2.2%	6 2.8%	4 1.7%
ASAT, high	2 0.9%	7 3.2%	4 1.7%
BUN/Creatinine ratio, high	11 4.9%	7 3.2%	5 2.1%
Calcium, low	0 0%	0 0%	1 0.4%
Carbon dioxide content/Bicarbonate, low	3 1.3%	2 0.9%	2 0.8%
Cholesterol, high	11 4.9%	4 1.8%	7 3%
Creatine Kinase, high	5 2.2%	2 0.9%	6 2.5%
Creatinine, high	3 1.3%	3 1.4%	5 2.1%
Direct Bilirubin, high	2 0.9%	1 0.5%	1 0.4%
GGT, high	5 2.2%	7 3.2%	7 3%
Glucose, low	17 7.6%	24 11%	13 5.5%
Glucose, high	54 24.2%	42 19.3%	54 22.9%
HDL Cholesterol, direct, low	3 1.3%	0 0%	2 0.8%
LDL Cholesterol, high	35 15.7%	29 13.3%	40 16.9%
Magnesium, low	0 0%	1 0.5%	0 0%
Phosphorus, inorganic, high	0 0%	0 0%	1 0.4%
Potassium, high	2 0.9%	10 4.6%	9 3.8%
Sodium, high	0 0%	1 0.5%	1 0.4%
Total Bilirubin, high	2 0.9%	1 0.5%	1 0.4%
Triglycerides, high	1 0.4%	0 0%	0 0%
Urea/BUN, high	17 7.6%	12 5.5%	25 10.6%

12. Secondary Outcome

Title	Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss)
Description	AUCτss of SB-742457 was estimated via nonlinear mixed effect analysis. This pharmacokinetic(PK) model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.
Time Frame	Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

Outcome Measure Data

Analysis Population Description

PK population included all participants for whom a pharmacokinetic sample was obtained and analyzed.

Arm/Group Title	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	215	233
Geometric Mean (Geometric Coefficient of Variation) [Nanogram hour per milliliter (ng*h/mL)]	1640.76 (35.96)	4160.29 (31.67)

13. Secondary Outcome

Title	Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss)
Description	Cmin-ss was estimated via nonlinear mixed effect analysis. This PK model was a steady state one compartment model with first-order absorption, with between participant variability on clearance and volume of distribution.
Time Frame	Post-dose at 3, 8 and 24 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

Outcome Measure Data

Analysis Population Description

PK population.

Arm/Group Title	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	215	233
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	53.42 (38.58)	135.05 (33.08)

14. Secondary Outcome

Title	Exposure Estimates for Donepezil (Cavgss)
Description	Participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) were allowed to participate in this study. Cavgss for donepezil approximately 12 to 20 hours after dosing were summarized by donepezil dose level 5 mg/7.5 mg/10 mg/15 mg.
Time Frame	Post-dose at 12 to 20 hours on Week 0, 1, 3, 6, 12, 18, 24, 30, 36, 42 and 48

Outcome Measure Data

Analysis Population Description

Donepezil PK population comprised of participants who received a stable dose of donepezil 5 mg/7.5 mg/10 mg/15 mg. Analysis is exclusively for Cavgss of donepezil therefore the two arms SB-742457 15 mg and SB-742457 35 mg have not been presented.

Arm/Group Title	Donepezil 5 mg	Donepezil 7.5 mg	Donepezil 10 mg	Donepezil 15 mg
Arm/Group Description	Participants received a stable dose of donepezil 5 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.	Participants received a stable dose of donepezil 7.5 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.	Participants received a stable dose of donepezil 10 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.	Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Measure Participants	179	1	484	1
Geometric Mean (Geometric Coefficient of Variation) [ng/mL]	20.72 (45.07)	17.68 (NA)	39.79 (46.62)	36.60 (NA)

15. Secondary Outcome

Title	Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene
Description	Genetic analyses was conducted to assess the effect of APOE4 carriage. ADAS-cog assessed a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items were evaluated by tests, but some were dependent on clinician ratings on a five-point scale. There were in all 11 questions. Total scores were calculated as the sum of the individual components. Scores ranged from 0 to 70 with higher scores indicating greater dysfunction. The ADAS-Cog total score was the sum of the calculated scores for questions 1, 2, and 7, and the scores were recorded on the CRF for questions 3 to 6 and 8 to 11. When a score was missing for one of the questions, the total score was calculated as a weighted average of the scores provided for the remaining ten questions. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.
Time Frame	Baseline (Week 0) to Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

PGx ITT Population consisted of all participants in the ITT population who had evaluable PGx data. Only those participants with APOE gene and available at the specified time point were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	206	202	219
Week 24	1.9 (5.58)	1.0 (6.63)	-0.1 (5.40)
Week 48	4.7 (6.52)	4.2 (7.46)	1.8 (5.72)

16. Secondary Outcome

Title	Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene
Description	Genetic analyses was conducted to assess the effect of APOE4 carriage. The CDR-SB is an interviewer administered scale and impairment is scored in following categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment was scored on a scale in which none =0, questionable =0.5, mild =1, moderate =2 and severe =3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher score indicating severe impairment. If there were any missing items then CDR-SB was set to missing and was not imputed. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.
Time Frame	Baseline (Week 0) to Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

PGx ITT Population. Only those participants with APOE gene and available at the specified time point were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	206	202	219
Week 24	1.1 (2.02)	0.6 (1.59)	0.8 (1.47)
Week 48	1.8 (1.98)	1.5 (2.11)	1.4 (1.92)

17. Secondary Outcome

Title	Change From Baseline in RBANS Scale in Participants With APOE4 Gene
Description	Genetic analyses was conducted to assess the effect of APOE4 carriage. RBANS is an individually administered cognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). Total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where a low score indicates greater impairment. Baseline was Week 0 value. The change from Baseline was obtained by subtracting the Baseline value from the post-randomization value.
Time Frame	Baseline (Week 0) to Week 24 and Week 48

Outcome Measure Data

Analysis Population Description

PGx ITT Population. Only those participants with APOE gene and available at the specified time point were analyzed.

Arm/Group Title	Donepezil + Placebo	Donepezil + SB-742457 15 mg	Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Measure Participants	206	202	219
Week 24	-5.2 (14.30)	-6.0 (20.07)	-6.0 (14.84)
Week 48	-7.7 (16.46)	-11.3 (16.13)	-5.9 (14.04)

Adverse Events

Time Frame	AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal).
Adverse Event Reporting Description	Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Arm/Group Title	Donepezil + Placebo		Donepezil + SB-742457 15 mg		Donepezil + SB-742457 35 mg
Arm/Group Description	Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.		Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.		Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
All Cause Mortality
	Donepezil + Placebo		Donepezil + SB-742457 15 mg		Donepezil + SB-742457 35 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/225 (0.4%)		5/221 (2.3%)		4/236 (1.7%)
Serious Adverse Events
	Donepezil + Placebo		Donepezil + SB-742457 15 mg		Donepezil + SB-742457 35 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	17/225 (7.6%)		26/221 (11.8%)		27/236 (11.4%)
Cardiac disorders
Bradycardia	0/225 (0%)		1/221 (0.5%)		1/236 (0.4%)
Adams-Stokes syndrome	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Angina pectoris	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Arteriosclerosis coronary artery	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Cardiac failure	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Cardio-respiratory arrest	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Sick sinus syndrome	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Ear and labyrinth disorders
Vertigo	0/225 (0%)		0/221 (0%)		2/236 (0.8%)
Gastrointestinal disorders
Abdominal pain upper	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Colonic polyp	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Diarrhoea	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Diverticulum	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Dyspepsia	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Oesophageal obstruction	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Vomiting	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
General disorders
Death	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Fatigue	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Pyrexia	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Hepatobiliary disorders
Biliary colic	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Infections and infestations
Pneumonia	3/225 (1.3%)		1/221 (0.5%)		3/236 (1.3%)
Urinary tract infection	1/225 (0.4%)		1/221 (0.5%)		0/236 (0%)
Abdominal abscess	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Bronchopneumonia	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Diverticulitis	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Erysipelas	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Influenza	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Respiratory tract infection	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Skin infection	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Injury, poisoning and procedural complications
Fall	2/225 (0.9%)		0/221 (0%)		0/236 (0%)
Humerus fracture	1/225 (0.4%)		0/221 (0%)		1/236 (0.4%)
Femur fracture	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Hand fracture	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Hip fracture	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Joint dislocation	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Lower limb fracture	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Post procedural haemorrhage	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Radius fracture	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Skin laceration	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Skull fracture	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Splenic injury	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Subdural haematoma	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Metabolism and nutrition disorders
Dehydration	1/225 (0.4%)		1/221 (0.5%)		0/236 (0%)
Decreased appetite	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Musculoskeletal and connective tissue disorders
Neck pain	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric cancer	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Glioblastoma	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Malignant melanoma	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Oesophageal carcinoma	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Penile neoplasm	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Squamous cell carcinoma	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Nervous system disorders
Cerebrovascular accident	1/225 (0.4%)		3/221 (1.4%)		1/236 (0.4%)
Syncope	1/225 (0.4%)		1/221 (0.5%)		2/236 (0.8%)
Cerebral haemorrhage	0/225 (0%)		2/221 (0.9%)		0/236 (0%)
Aphasia	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Dementia Alzheimer's type	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Dizziness	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Epilepsy	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Loss of consciousness	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Psychomotor hyperactivity	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Sciatica	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Transient ischaemic attack	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Psychiatric disorders
Confusional state	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Disorientation	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Renal and urinary disorders
Urethral stenosis	0/225 (0%)		1/221 (0.5%)		0/236 (0%)
Reproductive system and breast disorders
Metrorrhagia	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Dyspnoea	1/225 (0.4%)		0/221 (0%)		0/236 (0%)
Epistaxis	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Vascular disorders
Circulatory collapse	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Deep vein thrombosis	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Haematoma	0/225 (0%)		0/221 (0%)		1/236 (0.4%)
Other (Not Including Serious) Adverse Events
	Donepezil + Placebo		Donepezil + SB-742457 15 mg		Donepezil + SB-742457 35 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	41/225 (18.2%)		32/221 (14.5%)		33/236 (14%)
Infections and infestations
Nasopharyngitis	17/225 (7.6%)		19/221 (8.6%)		18/236 (7.6%)
Urinary tract infection	15/225 (6.7%)		10/221 (4.5%)		13/236 (5.5%)
Injury, poisoning and procedural complications
Fall	12/225 (5.3%)		4/221 (1.8%)		5/236 (2.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.