Trial Outcomes & Findings for Study of SB-742457 or Donepezil Versus Placebo in Subjects With Mild-to-moderate Alzheimer's Disease (NCT NCT00708552)

NCT ID: NCT00708552

Last Updated: 2018-07-27

Results Overview

ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a five point scale. The ADAS-Cog total score is the sum of the calculated scores for Questions 1 (Word recall task), 2 (Naming objects and fingers), and 7 (Word recognition task) and the scores recorded on the CRF for Questions 3 to 6 (Commands, Constructional praxis, Ideational praxis, Orientation) and 8 to 11 (Remembering test instructions, Spoken language ability, Word finding difficulty in spontaneous speech, Comprehension). The total score ranges from 0-70 with higher scores indicating greater dysfunction while lower indicates better cognitive function. Baseline was defined as the value at Week 0. Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 576 participants
• Primary outcome timeframe: Baseline (Week 0) and Week 24
• Results posted on: 2018-07-27

Participant Flow

This study was conducted at 68 centers in the following 11 countries: Bulgaria, Chile, Czech Republic, Estonia, Germany, Greece, Korea, Mexico, Poland, Russia, and South Africa from 04 July 2008 to 09 Mar 2010 and a total of 967 participants were screened over the recruitment period of 55 weeks.

Of 967 participants screened, 618 (349 screen failures) entered into the placebo run-in period and a total of 576 (42 placebo run-in failures) were randomized of which 2 participants did not take study medication, formed Safety population (574) comprising of randomized participants who took atleast one dose of study medication.

Participant milestones

Measure	Placebo Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg Participants received one tablet of SB-742457-15 milligrams (mg) and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Overall Study STARTED	145	145	133	151
Overall Study COMPLETED	118	127	118	130
Overall Study NOT COMPLETED	27	18	15	21

Reasons for withdrawal

Measure	Placebo Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg Participants received one tablet of SB-742457-15 milligrams (mg) and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Overall Study Adverse Event	10	3	4	6
Overall Study Lack of Efficacy	0	4	1	0
Overall Study Protocol Violation	0	0	2	4
Overall Study Lost to Follow-up	4	2	0	1
Overall Study Physician Decision	1	2	0	0
Overall Study Withdrawal by Subject	12	7	8	10

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Placebo n=135 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=142 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=130 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=147 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.	Total n=554 Participants Total of all reporting groups
Age, Continuous	73.3 Years STANDARD_DEVIATION 6.80 • n=5 Participants	72.4 Years STANDARD_DEVIATION 8.12 • n=7 Participants	72.5 Years STANDARD_DEVIATION 7.38 • n=5 Participants	71.1 Years STANDARD_DEVIATION 7.49 • n=4 Participants	72.3 Years STANDARD_DEVIATION 7.49 • n=21 Participants
Sex: Female, Male Female	87 Participants n=5 Participants	96 Participants n=7 Participants	75 Participants n=5 Participants	95 Participants n=4 Participants	353 Participants n=21 Participants
Sex: Female, Male Male	48 Participants n=5 Participants	46 Participants n=7 Participants	55 Participants n=5 Participants	52 Participants n=4 Participants	201 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	3 Participants n=5 Participants	9 Participants n=7 Participants	5 Participants n=5 Participants	9 Participants n=4 Participants	26 Participants n=21 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	6 Participants n=4 Participants	23 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	2 Participants n=4 Participants	3 Participants n=21 Participants
Race (NIH/OMB) White	128 Participants n=5 Participants	126 Participants n=7 Participants	118 Participants n=5 Participants	130 Participants n=4 Participants	502 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: ITT population. Only those participants with data available at the indicated time point were analyzed.

ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a five point scale. The ADAS-Cog total score is the sum of the calculated scores for Questions 1 (Word recall task), 2 (Naming objects and fingers), and 7 (Word recognition task) and the scores recorded on the CRF for Questions 3 to 6 (Commands, Constructional praxis, Ideational praxis, Orientation) and 8 to 11 (Remembering test instructions, Spoken language ability, Word finding difficulty in spontaneous speech, Comprehension). The total score ranges from 0-70 with higher scores indicating greater dysfunction while lower indicates better cognitive function. Baseline was defined as the value at Week 0. Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=116 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=124 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=115 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=123 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24	-0.3 Score on scale Standard Error 0.56	0.8 Score on scale Standard Error 0.58	0.4 Score on scale Standard Error 0.62	-0.5 Score on scale Standard Error 0.45

PRIMARY outcome

Timeframe: Week 24

Population: ITT population. Only those participants with data available at the indicated time point were analyzed.

The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse).

Outcome measures

Measure	Placebo n=118 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=125 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=117 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=127 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Clinician's Interview-Based Impression of Change - Plus (CIBIC+) Score at Week 24	4.0 Score on scale Standard Error 0.11	4.2 Score on scale Standard Error 0.10	3.9 Score on scale Standard Error 0.10	3.7 Score on scale Standard Error 0.10

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: ITT population. Only those participants available at the specified time point were analyzed.

RBANS is an individually administered neurocognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). The scale is completed by a trained and experienced neurologist, psychiatrist or neuropsychologist, or another trained and experienced person. It is preferred that this individual is the same person who administers the ADAS-Cog, but he/she must be a separate individual from the person who completes the CIBIC+. The scale is based on the performance of the participant and takes approximately 25-30 minutes to administer. Raw total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where low score= (greater impairment) and high score=(better cognitive function). Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=116 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=125 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=115 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=127 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24	-2.3 Score on scale Standard Error 1.44	-4.0 Score on scale Standard Error 1.42	-4.4 Score on scale Standard Error 1.49	-0.3 Score on scale Standard Error 1.21

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Intent-to-Treat (Baseline MMSE 16-26) which comprised of participants who had a baseline MMSE score of 16-26. Only those participants available at the specified time point were analyzed.

The MMSE was used to measure cognitive impairment. The MMSE consists of 11 tests namely orientation to time, orientation to place, registration, attention and calculation, recall, naming, repetition, comprehension, reading, writing and drawing corresponding to 5 domains orientation, memory, attention, and construction. All items were scored as 0 (incorrect response) or 1 (correct response). Total scores ranges from 0 to 30, with lower scores indicating greater cognitive impairment and higher scores indicating better function. Stratification by Baseline severity, using MMSE score at Baseline, with the strata being MMSE score of 10-15, 16-20 and 21-26. Two subgroups using MMSE score at Baseline were also examined, moderate 10-20 and mild 16-26. Data has been presented for participants with Baseline MMSE 16-26. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=99 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=110 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=98 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=113 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline Mini Mental State Examination [MMSE] Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24 MMSE Score 16-26 on ADAS-Cog total score	-1.3 Score on scale Standard Error 0.55	0.1 Score on scale Standard Error 0.66	-0.4 Score on scale Standard Error 0.73	-1.0 Score on scale Standard Error 0.53
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline Mini Mental State Examination [MMSE] Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24 MMSE Score 16-26 on RBANS total score	-1.3 Score on scale Standard Error 1.61	-2.4 Score on scale Standard Error 1.74	-2.8 Score on scale Standard Error 1.82	1.1 Score on scale Standard Error 1.52

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Intent-to-Treat (Baseline MMSE 10-20) which comprised of participants who had a baseline MMSE score of 16-26. Only those participants available at the specified time point were analyzed.

The MMSE was used to measure cognitive impairment. The MMSE consists of 11 tests namely orientation to time, orientation to place, registration, attention and calculation, recall, naming, repetition, comprehension, reading, writing and drawing corresponding to 5 domains orientation, memory, attention, and construction. All items were scored as 0 (incorrect response) or 1 (correct response). Total scores ranges from 0 to 30, with lower scores indicating greater cognitive impairment and higher scores indicating better function. Stratification by Baseline severity, using MMSE score at Baseline, with the strata being MMSE score of 10-15, 16-20 and 21-26. Two subgroups using MMSE score at Baseline were also examined, moderate 10-20 and mild 16-26. Data has been presented for participants with Baseline MMSE 10-20. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=92 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=94 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=89 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=95 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline [MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24 MMSE Score 10-20 on ADAS-Cog total score	0.0 Score on scale Standard Error 0.71	1.6 Score on scale Standard Error 0.76	1.3 Score on scale Standard Error 0.73	-0.1 Score on scale Standard Error 0.58
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline [MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 24 MMSE Score 10-20 on RBANS total score	-3.7 Score on scale Standard Error 1.79	-5.8 Score on scale Standard Error 1.73	-4.8 Score on scale Standard Error 1.68	-1.0 Score on scale Standard Error 1.44

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Intent-to-Treat (Baseline MMSE 16-26). Only those participants with data available at the indicated time point were analyzed.

The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse). Stratification by Baseline severity, using MMSE score at Baseline, with the strata being MMSE score of 10-15, 16-20 and 21-26. Two subgroups using MMSE score at Baseline were also examined, moderate 10-20 and mild 16-26. Data has been presented for participants with Baseline MMSE 16-26. Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=88 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=100 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=87 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=95 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 24	3.8 Score on scale Standard Error 0.12	4.0 Score on scale Standard Error 0.12	3.7 Score on scale Standard Error 0.11	3.5 Score on scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Intent-to-Treat (Baseline MMSE 10-20). Only those participants with data available at the indicated time point were analyzed.

The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse). Higher scores indicate worst outcome. Stratification by Baseline severity, using MMSE score at Baseline, with the strata being MMSE score of 10-15, 16-20 and 21-26. Two subgroups using MMSE score at Baseline were also examined, moderate 10-20 and mild 16-26. Data has been presented for participants with baseline MMSE 10-20. Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=79 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=80 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=80 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=85 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 24	4.2 Score on scale Standard Error 0.15	4.4 Score on scale Standard Error 0.13	4.1 Score on scale Standard Error 0.12	3.9 Score on scale Standard Error 0.12

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT population. Only those participants with data available at the indicated time point were analyzed.

ADAS-Cog assesses a range of cognitive abilities including memory, comprehension, orientation in time and place and spontaneous speech. Most items are evaluated by tests, but some are dependent on clinician ratings on a five point scale. The ADAS-Cog total score is the sum of the calculated scores for Questions 1 (Word recall task), 2 (Naming objects and fingers), and 7 (Word recognition task) and the scores recorded on the CRF for Questions 3 to 6 (Commands, Constructional praxis, Ideational praxis, Orientation) and 8 to 11 (Remembering test instructions, Spoken language ability, Word finding difficulty in spontaneous speech, Comprehension). The total score ranges from 0-70 with higher scores indicating greater dysfunction while lower indicates better cognitive function. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 12.

Outcome measures

Measure	Placebo n=124 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=133 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=126 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=137 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in ADAS-Cog Total Score at Week 12	-0.1 Score on scale Standard Error 0.45	0.0 Score on scale Standard Error 0.46	-0.2 Score on scale Standard Error 0.45	-0.6 Score on scale Standard Error 0.40

SECONDARY outcome

Timeframe: Week 12

Population: ITT population. Only those participants with data available at the indicated time point were analyzed.

The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse).

Outcome measures

Measure	Placebo n=126 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=133 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=126 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=139 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
CIBIC+ Score at Week 12	3.9 Score on scale Standard Error 0.08	4.0 Score on scale Standard Error 0.08	3.9 Score on scale Standard Error 0.09	3.7 Score on scale Standard Error 0.08

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: ITT population. Only those participants with data available at the indicated time point were analyzed.

RBANS is an individually administered neurocognitive battery comprising 12 subtests across five domains (Attention, Language, Visuospatial/Constructional Abilities, and Immediate and Delayed memory). The scale is completed by a trained and experienced neurologist, psychiatrist or neuropsychologist, or another trained and experienced person. It is preferred that this individual is the same person who administers the ADAS-Cog, but he/she must be a separate individual from the person who completes the CIBIC+. The scale is based on the performance of the participant and takes approximately 25-30 minutes to administer. Raw total scores are calculated by adding up the scores for each of the 12 individual subtests and ranges between 0 and 311, where low score= (greater impairment) and high score=(better cognitive function). Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 12.

Outcome measures

Measure	Placebo n=125 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=134 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=125 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=138 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in RBANS Total Score at Week 12	-6.7 Score on scale Standard Error 1.16	-8.7 Score on scale Standard Error 1.24	-5.9 Score on scale Standard Error 1.11	-3.4 Score on scale Standard Error 1.06

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Intent-to-Treat (Baseline MMSE 16-26). Only those participants available at the specified time-points were analyzed.

The MMSE was used to measure cognitive impairment. The MMSE consists of 11 tests namely orientation to time, orientation to place, registration, attention and calculation, recall, naming, repetition, comprehension, reading, writing and drawing corresponding to 5 domains orientation, memory, attention, and construction. All items were scored as 0 (incorrect response) or 1 (correct response). Total scores ranges from 0 to 30, with lower scores indicating greater cognitive impairment and higher scores indicating better function. Stratification by Baseline severity, using MMSE score at Baseline, with the strata being MMSE score of 10-15, 16-20 and 21-26. Two subgroups using MMSE score at Baseline were also examined, moderate 10-20 and mild 16-26. Data has been presented for Participants with Baseline MMSE score 16-26. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 12.

Outcome measures

Measure	Placebo n=99 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=110 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=98 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=113 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12 MMSE Score 16-26 on ADAS-Cog total score	-0.6 Score on scale Standard Error 0.48	-0.4 Score on scale Standard Error 0.47	-0.5 Score on scale Standard Error 0.52	-0.5 Score on scale Standard Error 0.42
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12 MMSE Score 16-26 on RBANS total score	-7.5 Score on scale Standard Error 1.28	-8.3 Score on scale Standard Error 1.51	-4.4 Score on scale Standard Error 1.35	-3.3 Score on scale Standard Error 1.31

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12

Population: Intent-to-Treat (Baseline MMSE 10-20). Only those participants available at the specified time-points were analyzed.

The MMSE was used to measure cognitive impairment. The MMSE consists of 11 tests namely orientation to time, orientation to place, registration, attention and calculation, recall, naming, repetition, comprehension, reading, writing and drawing corresponding to 5 domains orientation, memory, attention, and construction. All items were scored as 0 (incorrect response) or 1 (correct response). Total scores ranges from 0 to 30, with lower scores indicating greater cognitive impairment and higher scores indicating better function. Stratification by Baseline severity, using MMSE score at Baseline, with the strata being MMSE score of 10-15, 16-20 and 21-26. Two subgroups using MMSE score at Baseline were also examined, moderate 10-20 and mild 16-26. Data has been presented for participants with Baseline MMSE score 10-20. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 12.

Outcome measures

Measure	Placebo n=92 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=94 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=89 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=95 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12 MMSE Score 10-20 on ADAS-Cog total score	0.4 Score on scale Standard Error 0.51	0.4 Score on scale Standard Error 0.61	0.2 Score on scale Standard Error 0.60	-0.9 Score on scale Standard Error 0.51
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the Change From Baseline in ADAS-Cog Total Score, the Change From Baseline in RBANS Total Score at Week 12 MMSE Score 10-20 on RBANS total score	-6.4 Score on scale Standard Error 1.36	-10.0 Score on scale Standard Error 1.29	-6.8 Score on scale Standard Error 1.26	-1.7 Score on scale Standard Error 1.20

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-Treat (Baseline MMSE 16-26). Only those participants with data available at the indicated time point were analyzed.

The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse). Stratification by Baseline severity, using MMSE score at Baseline, with the strata being MMSE score of 10-15, 16-20 and 21-26. Two subgroups using MMSE score at Baseline were also examined, moderate 10-20 and mild 16-26. Data has been presented for participants with Baseline MMSE score 16-26.

Outcome measures

Measure	Placebo n=94 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=104 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=94 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=107 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 16-26) on the CIBIC+ Score at Week 12	3.8 Score on scale Standard Error 0.08	3.8 Score on scale Standard Error 0.09	3.7 Score on scale Standard Error 0.10	3.6 Score on scale Standard Error 0.08

SECONDARY outcome

Timeframe: Week 12

Population: Intent-to-Treat (Baseline MMSE 10-20). Only those participants with data available at the indicated time point were analyzed.

The CIBIC+ is a rating scale derived from an interview with the participant and caregiver with an independent rater designed to measure several domains of participant function, such as mental/cognitive state, behavior, and functioning. The scores are rated on a scale of 1 to 7 as follows: 1 (marked improvement), 2 (moderately improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (moderately worse) and 7 (markedly worse). Stratification by Baseline severity, using MMSE score at Baseline, with the strata being MMSE score of 10-15, 16-20 and 21-26. Two subgroups using MMSE score at Baseline were also examined, moderate 10-20 and mild 16-26. Data has been presented for participants with Baseline MMSE score 10-20.

Outcome measures

Measure	Placebo n=86 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=88 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=87 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=90 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Effect of Baseline Severity (Including Subgroup Analyses Based on Baseline MMSE Scores 10-20) on the CIBIC+ Score at Week 12	4.0 Score on scale Standard Error 0.10	4.1 Score on scale Standard Error 0.10	4.1 Score on scale Standard Error 0.11	3.7 Score on scale Standard Error 0.11

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 12 and 24

Population: ITT population. Only those participants available at the specified time points were analyzed.

The ADCS-ADL measures functional impairment in terms of activities of daily living. The ADCS-ADL is an interviewer-administered informant-based scale where the informant (caregiver) responds to 23 activities of daily living questions (i.e. those necessary for personal care, communicating and interacting with other people, maintaining a household, conducting hobbies and interests, making judgments and decisions) about the participant. The questions range 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 signifies greater functional ability and lower scores indicating greater impairment. The total score is the sum of all items and sub-questions. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Weeks 12 and 24.

Outcome measures

Measure	Placebo n=135 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=142 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=130 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=147 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score at Weeks 12 and 24 ADCS-ADL Total score at Week 12	-0.4 Score on scale Standard Error 0.59	-1.1 Score on scale Standard Error 0.65	-0.1 Score on scale Standard Error 0.64	0.2 Score on scale Standard Error 0.62
Change From Baseline in Alzheimer's Disease Cooperative Study - Activities of Daily Living (ADCS-ADL) Total Score at Weeks 12 and 24 ADCS-ADL Total score at Week 24	-1.0 Score on scale Standard Error 0.71	-1.4 Score on scale Standard Error 0.68	-1.1 Score on scale Standard Error 0.81	-1.2 Score on scale Standard Error 0.82

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: ITT population. Only those participants with data available at the indicated time point were analyzed.

The CSDD is used to assess signs and symptoms of major depression in demented participants. The CSDD scale contains 19 items on mood-related signs of depression, behavioral disturbance, physical signs of depression, cyclic functions and ideational disturbances, where each item is rated for severity on a scale of 0-2 (0=absent, 1=mild/intermittent, 2=severe). Scores above 10 (probable major depression),scores above 18 (definite major depression), scores below 6 (absence of significant depressive symptoms). The total score was calculated as a weighted average of the scores provided for the remaining 18 questions as follows: Imputed Total= Observed Total Score x 1+ Maximum Score of the missing value/ Sum of the Maximum Score of the non -missing values) and ranges from 0-38. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=118 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=125 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=117 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=128 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Cornell Scale for Depression in Dementia (CSDD) Total Score at Week 24	0.0 Score on scale Standard Error 0.26	-0.1 Score on scale Standard Error 0.25	0.3 Score on scale Standard Error 0.26	0.3 Score on scale Standard Error 0.25

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: ITT population. Only those participants with data available at the indicated time point were analyzed.

The MMSE is used to test for cognitive dysfunction. The scale is completed by a trained and experienced neurologist/psychiatrist/neuropsychologist based on the performance of the participants, and takes approximately 5 to 10 minutes to administer. It consists of 11 tests namely orientation to time, orientation to place, registration, attention and calculation, recall, naming, repetition, comprehension, reading, writing, drawing across 5 sections (orientation, registration, attention-calculation, recall, and language). Scoring was done by circling 0 if the response was incorrect, or 1 if the response was correct. Scores range from 0 to 30, with lower scores indicating greater cognitive impairment and higher scores indicating better cognitive function. The total MMSE score was a sum of all item scores. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=118 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=124 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=117 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=128 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in MMSE Total Score at Week 24	-0.3 Score on scale Standard Error 0.29	-0.3 Score on scale Standard Error 0.28	-0.1 Score on scale Standard Error 0.29	0.5 Score on scale Standard Error 0.27

SECONDARY outcome

Timeframe: Baseline (Week 0) and Weeks 12 and 24

Population: ITT population. Only those participants available at the specified time points were analyzed.

Basic score was calculated as the sum of questions 1-6b and ranges from 0-22 (activities included are: eating, walking, using the toilet, bathing, grooming and dressing) and Instrumental score, sum of questions 7-23, ranges from 0-56 (activities included are: using the telephone, watching television, conversations, clearing dishes, personal belongings, making drinks, making snacks, taking rubbish out, getting out and about, shopping, keeping appointments, being left alone, current events, reading, writing, pastimes/hobbies, household chores). Total independence score is calculated by re-scoring the individual questions for each activity. The total independence score therefore ranges between 0 to 23, where 23 indicates that a participant is independent (based on these 23 ADL). Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Weeks 12 and 24.

Outcome measures

Measure	Placebo n=135 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=142 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=130 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=147 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24 Basic score at Week 12	-0.6 Score on scale Standard Error 0.17	-0.5 Score on scale Standard Error 0.19	-0.4 Score on scale Standard Error 0.24	-0.2 Score on scale Standard Error 0.17
Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24 Basic score at Week 24	-0.7 Score on scale Standard Error 0.20	-0.7 Score on scale Standard Error 0.19	-0.6 Score on scale Standard Error 0.24	-0.8 Score on scale Standard Error 0.23
Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24 Instrumental score at Week 12	0.2 Score on scale Standard Error 0.50	-0.6 Score on scale Standard Error 0.55	0.3 Score on scale Standard Error 0.52	0.4 Score on scale Standard Error 0.55
Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24 Instrumental score at Week 24	-0.3 Score on scale Standard Error 0.60	-0.7 Score on scale Standard Error 0.61	-0.5 Score on scale Standard Error 0.68	-0.4 Score on scale Standard Error 0.70
Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24 Total Independence Score at Week 12	-0.1 Score on scale Standard Error 0.23	-0.1 Score on scale Standard Error 0.23	0.2 Score on scale Standard Error 0.24	0.2 Score on scale Standard Error 0.23
Change From Baseline in ADCS-ADL-Basic Score; ADCS-ADL: Instrumental Score and ADCS-ADL: Total Independence Score at Weeks 12 and 24 Total Independence Score at Week 24	-0.3 Score on scale Standard Error 0.27	-0.2 Score on scale Standard Error 0.26	-0.1 Score on scale Standard Error 0.29	-0.1 Score on scale Standard Error 0.30

SECONDARY outcome

Timeframe: Upto Week 24

Population: Safety population.

An Adverse Event (AE) is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, may jeopardize the participant or require medical or surgical intervention to prevent one of the other outcomes listed in the definition above, or is an event of possible drug-induced liver injury. Number of participants with any adverse event (serious and non-serious) and SAEs were reported.

Outcome measures

Measure	Placebo n=145 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Number of Participants With Any Adverse Event (Serious and Non-serious) and Serious Adverse Events (SAEs) Any AE	45 Participants	42 Participants	39 Participants	65 Participants
Number of Participants With Any Adverse Event (Serious and Non-serious) and Serious Adverse Events (SAEs) Any SAE	7 Participants	7 Participants	3 Participants	10 Participants

SECONDARY outcome

Timeframe: Upto Week 24

Population: Safety population. Only those participants with data available at the indicated time point were analyzed.

Vital sign measurements included systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Heart Rate (HR), Body weight (BW). SBP and DBP and HR were measured once after the participant sat quietly for at least 5 minutes and in addition, upon standing to assess participants for postural hypotension. DBP was measured at the disappearance of Korotkoff sounds (Phase V). The plethysmographic method (preferably with a column sphygmomanometer where available) was used to measure blood pressure throughout the study. Body weight was measured, without shoes and wearing light clothing. The PCC range were as follows: SBP (Reference Range [RR] <90-140> Increase from Baseline [IFB]>=40 and decrease from baseline [DFB] >=30), DBP (RR < 50-90> IFB>=30 and DFB >=20), HR (RR <50-100> IFB >=30 and DFB >=30, BW (IFB >= 7% and DFB >=7%).

Outcome measures

Measure	Placebo n=140 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=143 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=149 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) SBP sitting ATOT <90 or > 140 and IFB >=40	1 Participants	2 Participants	2 Participants	0 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) SBP standing ATOT <90 or > 140 and IFB >=40	0 Participants	3 Participants	3 Participants	1 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) SBP standing ATOT <90 or > 140 and DFB >=30	0 Participants	0 Participants	0 Participants	4 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) SBP orthostatic, fall in SBP >30	0 Participants	0 Participants	3 Participants	1 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) DBP sitting ATOT <50 or > 90 and IFB >=30	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) DBP sitting ATOT <50 or > 90 and DFB >=20	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) DBP standing ATOT <50 or > 90 and IFB >=30	2 Participants	0 Participants	2 Participants	0 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) DBP standing ATOT <50 or > 90 and DFB >=20	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) DBP orthostatic, fall in SBP >20	0 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) HR sitting ATOT <50 or >100 and DFB >=30	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) HR standing ATOT <50 or >100 and IFB >=30	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) HR orthostatic, increase in HR>= >20	5 Participants	2 Participants	2 Participants	6 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) Weight, IFB>=7%	4 Participants	4 Participants	6 Participants	6 Participants
Number of Participants With Vital Signs Data of Potential Clinical Concern (PCC) Any Time on Treatment (ATOT) Weight, DFB>=7%	6 Participants	8 Participants	5 Participants	10 Participants

SECONDARY outcome

Timeframe: Upto Week 24

Population: Safety population. Only those participants available at the specified time point were analyzed.

Hematology parameters included hematocrit ratio (reference range males 0.410-0.500, females 0.350-0.460 [18-64 years] and males 0.360-0.490, females 0.330-0.460 [65+ years]), hemoglobin grams per liter (13.8-17.2), lymphocytes giga per liter (0.85-4.10), monocytes giga per liter (0.20-1.10), platelet count giga per liter (130-400), segmented neutrophils giga per liter (1.80-8.00), total neutrophils (1.80-8.00). Data has been presented in a consolidated format for hematology parameters high and low from the reference range of PCC ATOT.

Outcome measures

Measure	Placebo n=145 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Number of Participants With Hematology Data of PCC ATOT Hematocrit, ATOT, low	1 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Hematology Data of PCC ATOT Hemoglobin, ATOT. low	2 Participants	1 Participants	2 Participants	6 Participants
Number of Participants With Hematology Data of PCC ATOT Lymphocytes, ATOT, low	4 Participants	5 Participants	3 Participants	2 Participants
Number of Participants With Hematology Data of PCC ATOT Lymphocytes, ATOT, high	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Hematology Data of PCC ATOT Monocytes, ATOT, low	17 Participants	10 Participants	9 Participants	24 Participants
Number of Participants With Hematology Data of PCC ATOT Platelet count, ATOT, low	3 Participants	2 Participants	2 Participants	2 Participants
Number of Participants With Hematology Data of PCC ATOT Segmented neutrophils, ATOT, low	2 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Hematology Data of PCC ATOT Segmented neutrophils, ATOT, high	1 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Hematology Data of PCC ATOT Total neutrophils, ATOT, low	2 Participants	1 Participants	0 Participants	1 Participants
Number of Participants With Hematology Data of PCC ATOT Total neutrophils, ATOT, high	0 Participants	1 Participants	1 Participants	1 Participants
Number of Participants With Hematology Data of PCC ATOT White blood cell count, ATOT, low	2 Participants	0 Participants	1 Participants	1 Participants
Number of Participants With Hematology Data of PCC ATOT White blood cell count, ATOT, high	0 Participants	3 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Upto Week 24

Population: Safety population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included alanine amino transferase international units per liter (IU/L) RR [0-48], alkaline phosphatase IU/L (20-125), aspartate amino transferase international units per liter (0-55), blood urea nitrogen/creatinine ratio (24-101), calcium millimoles per liter (mmol/L) [2.12-2.56], carbon dioxide content/bicarbonate mmol/L (20-32), cholesterol mmol/L (0.00-5.15), creatine kinase IU/L (males 0-235 and females 0-190), creatinine micromoles per liter (umol/L) [44-124], direct bilirubin umol/L (0-6), gamma glutamyl transferase IU/L (males 0-65 and females 0-45), glucose mmol/L (3.9-6.9), low density lipoprotein cholesterol mmol/L (0.00-3.35), lactate dehydrogenase IU/L (0-270), potassium mmol/L (3.5-5.3), sodium mmol/L (135-146), total bilirubin umol/L (0-22), triglycerides mmol/L (0.00-2.24), urea/blood urea nitrogen mmol/L (2.5-10.5). Data has been presented in a consolidated format for clinical chemistry parameters high and low from the RR of PCC ATOT.

Outcome measures

Measure	Placebo n=145 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Number of Participants With Chemistry Data of PCC ATOT Alanine Amino Transferase, ATOT, high	2 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Chemistry Data of PCC ATOT Alkaline Phosphatase, ATOT, high	1 Participants	0 Participants	2 Participants	6 Participants
Number of Participants With Chemistry Data of PCC ATOT Aspartate Amino Transferase, ATOT, high	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Chemistry Data of PCC ATOT Blood urea nitrogen/Creatinine ratio, ATOT, high	1 Participants	4 Participants	0 Participants	3 Participants
Number of Participants With Chemistry Data of PCC ATOT Calcium, ATOT, low	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Chemistry Data of PCC ATOT Carbon dioxide content/Bicarbonate, ATOT, low	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Chemistry Data of PCC ATOT Cholesterol, ATOT, high	5 Participants	5 Participants	2 Participants	7 Participants
Number of Participants With Chemistry Data of PCC ATOT Creatine Kinase, ATOT, high	3 Participants	1 Participants	5 Participants	7 Participants
Number of Participants With Chemistry Data of PCC ATOT Creatinine, ATOT, high	3 Participants	1 Participants	4 Participants	1 Participants
Number of Participants With Chemistry Data of PCC ATOT Direct Bilirubin, ATOT, high	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Chemistry Data of PCC ATOT Gamma Glutamyl Transferase, ATOT, high	3 Participants	1 Participants	4 Participants	4 Participants
Number of Participants With Chemistry Data of PCC ATOT Glucose, ATOT, low	7 Participants	5 Participants	8 Participants	6 Participants
Number of Participants With Chemistry Data of PCC ATOT Glucose, ATOT, high	27 Participants	16 Participants	23 Participants	22 Participants
Number of Participants With Chemistry Data of PCC ATOT Low Density Lipoprotein Cholesterol, ATOT, high	21 Participants	26 Participants	12 Participants	25 Participants
Number of Participants With Chemistry Data of PCC ATOT Lactate Dehydrogenase, ATOT, high	0 Participants	1 Participants	0 Participants	0 Participants
Number of Participants With Chemistry Data of PCC ATOT Potassium, ATOT, high	5 Participants	5 Participants	2 Participants	7 Participants
Number of Participants With Chemistry Data of PCC ATOT Sodium, ATOT, low	0 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Chemistry Data of PCC ATOT Sodium, ATOT, high	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Chemistry Data of PCC ATOT Total Bilirubin, ATOT, high	1 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Chemistry Data of PCC ATOT Triglycerides, ATOT, high	0 Participants	0 Participants	0 Participants	1 Participants
Number of Participants With Chemistry Data of PCC ATOT Urea/Blood urea nitrogen, ATOT, high	7 Participants	6 Participants	8 Participants	4 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants available at the specified time point were analyzed.

Clinical chemistry parameters included alanine amino transferase, alkaline phosphatase, aspartate amino transferase, creatine kinase, gamma glutamyl transferase and lactate dehydrogenase. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Weeks 24.

Outcome measures

Measure	Placebo n=145 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24 Alanine amino transferase at Week 24	-0.3 IU/L Standard Deviation 8.76	0.0 IU/L Standard Deviation 4.88	-0.1 IU/L Standard Deviation 6.77	1.6 IU/L Standard Deviation 29.47
Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24 Alkaline phosphatase at Week 24	-3.4 IU/L Standard Deviation 15.71	-0.1 IU/L Standard Deviation 10.91	0.8 IU/L Standard Deviation 14.63	2.0 IU/L Standard Deviation 17.81
Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24 Aspartate amino transferase at Week 24	-0.3 IU/L Standard Deviation 6.15	0.0 IU/L Standard Deviation 3.80	-0.1 IU/L Standard Deviation 6.88	0.5 IU/L Standard Deviation 12.88
Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24 Creatine kinase at Week 24	-16.8 IU/L Standard Deviation 242.93	-5.4 IU/L Standard Deviation 47.97	16.2 IU/L Standard Deviation 157.67	0.6 IU/L Standard Deviation 82.86
Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24 Gamma glutamyl transferase at Week 24	-1.5 IU/L Standard Deviation 13.06	-0.2 IU/L Standard Deviation 11.23	-1.3 IU/L Standard Deviation 15.08	3.6 IU/L Standard Deviation 32.97
Change From Baseline in Clinical Chemistry Parameters Alanine Amino Transferase, Alkaline Phosphatase, Aspartate Amino Transferase, Creatine Kinase, Gamma Glutamyl Transferase and Lactate Dehydrogenase at Week 24 Lactate dehydrogenase at Week 24	0.8 IU/L Standard Deviation 25.09	-2.9 IU/L Standard Deviation 28.88	-0.4 IU/L Standard Deviation 22.65	-1.2 IU/L Standard Deviation 25.99

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants with data available at the indicated time point were analyzed.

Clinical chemistry parameters included albumin and total protein. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=111 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=117 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=115 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=126 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein at Week 24 Albumin at Week 24	-0.5 grams per liter Standard Deviation 2.37	-0.5 grams per liter Standard Deviation 2.44	-0.6 grams per liter Standard Deviation 2.54	-0.8 grams per liter Standard Deviation 2.62
Change From Baseline in Clinical Chemistry Parameters Albumin and Total Protein at Week 24 Total protein at Week 24	-0.8 grams per liter Standard Deviation 3.52	-0.9 grams per liter Standard Deviation 4.00	-1.3 grams per liter Standard Deviation 3.50	-1.2 grams per liter Standard Deviation 3.62

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants with data available at the indicated time point were analyzed.

Clinical chemistry parameter included blood urea nitrogen /creatinine ratio. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=115 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=121 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=116 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=127 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Clinical Chemistry Parameter Blood Urea Nitrogen /Creatinine Ratio at Week 24	0.8 Ratio Standard Deviation 19.99	2.3 Ratio Standard Deviation 19.32	-3.7 Ratio Standard Deviation 17.44	-0.3 Ratio Standard Deviation 17.76

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants available at the specified time points were analyzed.

Clinical chemistry parameters included calcium, CO2 content/bicarbonate, chloride, glucose, HDL cholesterol, LDL cholesterol, magnesium, phosphorus, potassium, sodium, triglycerides, urea/blood urea nitrogen. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=145 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Calcium at Week 24	-0.008 mmol/L Standard Deviation 0.0910	-0.012 mmol/L Standard Deviation 0.0956	-0.025 mmol/L Standard Deviation 0.1215	-0.013 mmol/L Standard Deviation 0.0932
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 CO2 content/bicarbonate at Week 24	0.5 mmol/L Standard Deviation 2.91	0.3 mmol/L Standard Deviation 2.46	-0.5 mmol/L Standard Deviation 3.01	0.5 mmol/L Standard Deviation 2.84
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Chloride at Week 24	0.2 mmol/L Standard Deviation 2.54	0.3 mmol/L Standard Deviation 2.97	0.1 mmol/L Standard Deviation 2.87	-0.0 mmol/L Standard Deviation 2.70
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Glucose at Week 24	0.02 mmol/L Standard Deviation 1.108	0.03 mmol/L Standard Deviation 1.327	0.14 mmol/L Standard Deviation 1.808	0.07 mmol/L Standard Deviation 1.605
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 HDL cholesterol at Week 24	-0.023 mmol/L Standard Deviation 0.2272	-0.060 mmol/L Standard Deviation 0.2402	-0.060 mmol/L Standard Deviation 0.3050	-0.035 mmol/L Standard Deviation 0.2477
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 LDL cholesterol at Week 24	0.149 mmol/L Standard Deviation 0.8387	-0.032 mmol/L Standard Deviation 0.6176	-0.115 mmol/L Standard Deviation 0.5971	-0.032 mmol/L Standard Deviation 0.7417
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Magnesium at Week 24	-0.001 mmol/L Standard Deviation 0.0606	-0.007 mmol/L Standard Deviation 0.0538	-0.002 mmol/L Standard Deviation 0.0569	-0.001 mmol/L Standard Deviation 0.0591
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Phosphorus at Week 24	0.010 mmol/L Standard Deviation 0.1435	-0.018 mmol/L Standard Deviation 0.1529	0.043 mmol/L Standard Deviation 0.1728	0.026 mmol/L Standard Deviation 0.1752
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Potassium at Week 24	-0.00 mmol/L Standard Deviation 0.450	0.09 mmol/L Standard Deviation 0.458	0.04 mmol/L Standard Deviation 0.440	0.05 mmol/L Standard Deviation 0.450
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Sodium at Week 24	0.1 mmol/L Standard Deviation 2.24	0.0 mmol/L Standard Deviation 2.57	-0.2 mmol/L Standard Deviation 2.43	0.4 mmol/L Standard Deviation 2.31
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Triglycerides at Week 24	-0.040 mmol/L Standard Deviation 0.8750	-0.071 mmol/L Standard Deviation 0.7146	-0.024 mmol/L Standard Deviation 0.7678	0.082 mmol/L Standard Deviation 1.0874
Change From Baseline in Clinical Chemistry Parameters Calcium, CO2 Content/Bicarbonate, Chloride, Glucose, HDL Cholesterol, LDL Cholesterol, Magnesium, Phosphorus, Potassium, Sodium, Triglycerides, Urea/Blood Urea Nitrogen at Week 24 Urea/blood urea nitrogen at Week 24	0.06 mmol/L Standard Deviation 1.642	0.29 mmol/L Standard Deviation 1.510	0.14 mmol/L Standard Deviation 1.467	0.10 mmol/L Standard Deviation 1.453

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants with data available at the indicated time point were analyzed.

Clinical chemistry parameters included creatinine, direct bilirubin and total bilirubin. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=115 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=121 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=116 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=127 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Clinical Chemistry Parameters Creatinine, Direct Bilirubin and Total Bilirubin at Week 24 Creatinine at Week 24	-0.3 umol/L Standard Deviation 20.40	1.2 umol/L Standard Deviation 10.83	5.7 umol/L Standard Deviation 10.64	1.4 umol/L Standard Deviation 8.53
Change From Baseline in Clinical Chemistry Parameters Creatinine, Direct Bilirubin and Total Bilirubin at Week 24 Direct bilirubin at Week 24	-0.1 umol/L Standard Deviation 0.79	0.1 umol/L Standard Deviation 0.84	-0.1 umol/L Standard Deviation 1.17	-0.1 umol/L Standard Deviation 1.01
Change From Baseline in Clinical Chemistry Parameters Creatinine, Direct Bilirubin and Total Bilirubin at Week 24 Total bilirubin at Week 24	-0.1 umol/L Standard Deviation 3.33	-0.1 umol/L Standard Deviation 2.82	0.0 umol/L Standard Deviation 3.66	-0.8 umol/L Standard Deviation 3.89

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants with data available at the indicated time point were analyzed.

Hematology parameters included basophils, eosinophils, lymphocytes, monocytes, platelet count, segmented neutrophils, total neutrophils, white blood cell count. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=117 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=121 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=115 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=124 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 Basophils at Week 24	0.001 giga cells per liter Standard Deviation 0.0168	0.002 giga cells per liter Standard Deviation 0.0189	0.003 giga cells per liter Standard Deviation 0.0183	-0.001 giga cells per liter Standard Deviation 0.0173
Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 Eosinophils at Week 24	-0.011 giga cells per liter Standard Deviation 0.0923	-0.006 giga cells per liter Standard Deviation 0.0858	-0.004 giga cells per liter Standard Deviation 0.1272	-0.004 giga cells per liter Standard Deviation 0.0997
Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 Lymphocytes at Week 24	-0.037 giga cells per liter Standard Deviation 0.4182	-0.075 giga cells per liter Standard Deviation 0.4373	-0.151 giga cells per liter Standard Deviation 0.3949	-0.047 giga cells per liter Standard Deviation 0.5084
Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 Monocytes at Week 24	-0.002 giga cells per liter Standard Deviation 0.1415	-0.007 giga cells per liter Standard Deviation 0.1403	0.000 giga cells per liter Standard Deviation 0.1643	-0.008 giga cells per liter Standard Deviation 0.1306
Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 Platelet count at Week 24	-4.8 giga cells per liter Standard Deviation 33.13	-8.7 giga cells per liter Standard Deviation 32.33	-5.3 giga cells per liter Standard Deviation 36.83	-9.4 giga cells per liter Standard Deviation 36.13
Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 Segmented neutrophils at Week 24	0.002 giga cells per liter Standard Deviation 1.2619	0.015 giga cells per liter Standard Deviation 1.3909	0.163 giga cells per liter Standard Deviation 1.2329	-0.109 giga cells per liter Standard Deviation 1.1543
Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 Total neutrophils at Week 24	0.002 giga cells per liter Standard Deviation 1.2619	0.015 giga cells per liter Standard Deviation 1.3909	0.163 giga cells per liter Standard Deviation 1.2329	-0.110 giga cells per liter Standard Deviation 1.1550
Change From Baseline in Hematology Parameters Basophils, Eosinophils, Lymphocytes, Monocytes, Platelet Count, Segmented Neutrophils, Total Neutrophils, White Blood Cell Count at Week 24 White blood cell count at Week 24	-0.05 giga cells per liter Standard Deviation 1.357	-0.08 giga cells per liter Standard Deviation 1.551	0.01 giga cells per liter Standard Deviation 1.295	-0.17 giga cells per liter Standard Deviation 1.288

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants with data available at the indicated time point were analyzed.

Hematology parameter included hematocrit. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=118 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=122 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=116 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=124 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Hematology Parameter Hematocrit	0.0038 Ratio Standard Deviation 0.02264	0.0037 Ratio Standard Deviation 0.02242	-0.0003 Ratio Standard Deviation 0.02509	0.0002 Ratio Standard Deviation 0.02351

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants available at the specified time points were analyzed.

Hematology parameter included hemoglobin and mean corpuscle hemoglobin concentration. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=145 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Hematology Parameters Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Week 24 Hemoglobin at Week 24	-1.1 grams per liter Standard Deviation 7.24	-1.6 grams per liter Standard Deviation 7.40	-1.8 grams per liter Standard Deviation 8.06	-1.6 grams per liter Standard Deviation 7.55
Change From Baseline in Hematology Parameters Hemoglobin and Mean Corpuscle Hemoglobin Concentration at Week 24 Mean corpuscle hemoglobin concentration at Week 24	-5.3 grams per liter Standard Deviation 8.99	-5.9 grams per liter Standard Deviation 9.74	-3.9 grams per liter Standard Deviation 9.73	-4.2 grams per liter Standard Deviation 9.64

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants with data available at the indicated time point were analyzed.

Hematology parameter included mean corpuscle hemoglobin. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=114 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=117 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=113 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=122 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Hematology Parameter Mean Corpuscle Hemoglobin at Week 24	-0.21 picograms Standard Deviation 0.949	-0.19 picograms Standard Deviation 1.173	-0.10 picograms Standard Deviation 1.023	-0.08 picograms Standard Deviation 0.830

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants available at the specified time points were analyzed.

Hematology parameter included mean corpuscle volume and mean platelet volume. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=145 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Hematology Parameter Mean Corpuscle Volume and Mean Platelet Volume at Week 24 Mean corpuscle volume at Week 24	0.8 femtoliters Standard Deviation 2.84	1.4 femtoliters Standard Deviation 2.45	0.6 femtoliters Standard Deviation 2.35	0.9 femtoliters Standard Deviation 2.43
Change From Baseline in Hematology Parameter Mean Corpuscle Volume and Mean Platelet Volume at Week 24 Mean platelet volume at Week 24	-0.01 femtoliters Standard Deviation 0.711	-0.04 femtoliters Standard Deviation 0.626	0.13 femtoliters Standard Deviation 0.715	0.03 femtoliters Standard Deviation 0.627

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

Population: Safety population. Only those participants with data available at the indicated time point were analyzed.

Hematology parameter included red blood cell count. Baseline was defined as the value at Visit 3 (Week 0). Change from Baseline was obtained by subtracting the Baseline value from the post-randomization value at Week 24.

Outcome measures

Measure	Placebo n=114 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=117 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=113 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=122 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Change From Baseline in Hematology Parameter Red Blood Cell Count at Week 24	-0.03 trillion cells per liter Standard Deviation 0.276	0.01 trillion cells per liter Standard Deviation 0.256	-0.08 trillion cells per liter Standard Deviation 0.329	-0.07 trillion cells per liter Standard Deviation 0.262

SECONDARY outcome

Timeframe: Upto Week 24

Population: Safety population. Only those participants available at the specified time points were analyzed.

The clinical interpretation of the ECG by the investigator was recorded as Normal, Abnormal but not clinically significant (ANCS) and Abnormal clinically significant (ACS). ECG interpretation by the central cardiologist included the most extreme result of the available ECGs where the central cardiologist's interpretation of the ECG was recorded as Normal, Unable to Evaluate and Abnormal. Data has been presented for number of participants with most severe on-treatment abnormal ECG findings.

Outcome measures

Measure	Placebo n=145 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 Participants Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 Participants Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Number of Participants With Electrocardiogram (ECG) Findings as Assessed by Investigator and Central Cardiologist Investigator interpretion ANCS	58 Participants	60 Participants	59 Participants	67 Participants
Number of Participants With Electrocardiogram (ECG) Findings as Assessed by Investigator and Central Cardiologist Investigator interpretion ACS	0 Participants	1 Participants	0 Participants	2 Participants
Number of Participants With Electrocardiogram (ECG) Findings as Assessed by Investigator and Central Cardiologist Central cardiologist interpretation abnormal	49 Participants	51 Participants	51 Participants	59 Participants

SECONDARY outcome

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

Population: Pharmacokinetic concentration population comprised of all participants for whom a pharmacokinetic sample was obtained and analyzed. Only those participants with data available at the time of analysis were included.

A total of five pharmacokinetic samples per participant were collected for the purpose of assessing plasma concentrations of SB-742457 and donepezil. At each visit (Day 28±5, 56±5, 84±5, 126±5 and 168±5) one sample was collected post 24 hours of last dose.

Outcome measures

Measure	Placebo n=141 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=132 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Exposure Estimates for SB-742457 Area Under Curve Over the Dosing Interval at Steady State (AUCτss)	1434.89 nanograms hour per milliliter Geometric Coefficient of Variation 36.04	3424.91 nanograms hour per milliliter Geometric Coefficient of Variation 38.04	—	—

SECONDARY outcome

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

Population: Pharmacokinetic concentration population. Only those participants with data available at the time of analysis were included.

Blood sample for pharmacokinetic analysis, were obtained within 24 hours of last dose. A total of five pharmacokinetic samples per participants were taken at Weeks 4, 8,12,18 and Week 24. The SB-742457 exposures at steady state Cmin-ss for each participant were estimated via nonlinear mixed effect analysis. Data has been presented in a consolidated format for SB-742457 exposures at steady state Cmin-ss.

Outcome measures

Measure	Placebo n=141 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=132 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Exposure Estimates for SB-742457 Minimum Concentration at Steady State (Cmin-ss)	46.03 nanograms per milliliter Geometric Coefficient of Variation 109.69	37.47 nanograms per milliliter Geometric Coefficient of Variation 39.47	—	—

SECONDARY outcome

Timeframe: Weeks 4, 8,12,18 and Week 24

Population: Pharmacokinetic concentration population. Only those participants with data available at the time of analysis were included.

Blood sample for pharmacokinetic analysis, were obtained within 24 hours of last dose. A total of five pharmacokinetic samples per participants were taken at Weeks 4, 8,12,18 and Week 24. The Donepezil exposures at steady state Cavgss for each participant were estimated via nonlinear mixed effect analysis. Data has been presented in a consolidated format for SB-742457 exposures at steady state Cavgss.

Outcome measures

Measure	Placebo n=132 Participants Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=133 Participants Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Exposure Estimates for Donepezil Average Concentration at Steady State (Cavgss)	17.53 nanograms per milliliter Geometric Coefficient of Variation 50.51	31.80 nanograms per milliliter Geometric Coefficient of Variation 60.14	—	—

Adverse Events

Placebo

Serious events: 7 serious events

Other events: 42 other events

Deaths: 1 deaths

SB-742457-15mg

Serious events: 7 serious events

Other events: 39 other events

Deaths: 0 deaths

SB-742457-35mg

Serious events: 3 serious events

Other events: 38 other events

Deaths: 1 deaths

Donepezil

Serious events: 10 serious events

Other events: 62 other events

Deaths: 1 deaths

Serious adverse events

Measure	Placebo n=145 participants at risk Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 participants at risk Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 participants at risk Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 participants at risk Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Injury, poisoning and procedural complications Cardiac pacemaker malfunction	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Concussion	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Ear injury	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Femoral neck fracture	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Hip fracture	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Operative haemorrhage	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Pelvic fracture	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Post procedural complication	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Upper limb fracture	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Colitis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Gastritis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Gastritis erosive	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Rectal prolapse	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Cerebrovascular accident	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Dementia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Dementia Alzheimer's type	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Cardiac disorders Cardiac arrest	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Cardiac disorders Cardiac failure acute	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Endocarditis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Pneumonia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Back pain	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Metastases to liver	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Pancreatic carcinoma	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Delirium	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Renal and urinary disorders Bladder prolapse	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Renal and urinary disorders Nephrolithiasis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Blood and lymphatic system disorders Anaemia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Ear and labyrinth disorders External ear inflammation	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Hepatobiliary disorders Cholelithiasis	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders Cough	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Metabolism and nutrition disorders Hypoglycaemia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.

Other adverse events

Measure	Placebo n=145 participants at risk Participants received one tablet of matching placebo to SB-742457 (Week 1 to 4) and one capsule of matching placebo orally each evening just prior to going to bed (Week 4 to 24).	SB-742457-15mg n=145 participants at risk Participants received one tablet of SB-742457-15 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	SB-742457-35mg n=133 participants at risk Participants received one tablet of SB-742457-35 mg and one capsule of matching placebo to Donepezil orally each evening just prior to going to bed in the two treatment period (Week 1 to 4 and Week 4 to 24).	Donepezil n=151 participants at risk Participants received Donepezil capsule by one-step titration 5mg Donepezil once daily (Week 1 to Week 4) before up-titrating at Visit 4 (Week 4) to 10 mg once daily dose for the remaining 20 weeks of the treatment period (Week 4 to 24) along with matching placebo to SB-747457.
Infections and infestations Nasopharyngitis	2.1% 3/145 • Upto Week 24. Safety population was used for analysis.	2.1% 3/145 • Upto Week 24. Safety population was used for analysis.	2.3% 3/133 • Upto Week 24. Safety population was used for analysis.	2.6% 4/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Influenza	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	2.3% 3/133 • Upto Week 24. Safety population was used for analysis.	2.6% 4/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Urinary tract infection	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	2.8% 4/145 • Upto Week 24. Safety population was used for analysis.	2.3% 3/133 • Upto Week 24. Safety population was used for analysis.	2.0% 3/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Bronchitis	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	2.1% 3/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Cystitis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Erysipelas	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Gastroenteritis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Viral infection	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Conjunctivitis bacterial	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Fungal skin infection	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Gastroenteritis viral	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Gastrointestinal infection	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Herpes zoster	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Otitis media	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Rhinitis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Tooth infection	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Upper respiratory tract infection	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Infections and infestations Viral rhinitis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Headache	4.1% 6/145 • Upto Week 24. Safety population was used for analysis.	3.4% 5/145 • Upto Week 24. Safety population was used for analysis.	1.5% 2/133 • Upto Week 24. Safety population was used for analysis.	3.3% 5/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Dizziness	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	2.1% 3/145 • Upto Week 24. Safety population was used for analysis.	1.5% 2/133 • Upto Week 24. Safety population was used for analysis.	3.3% 5/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Syncope	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Dementia Alzheimer's type	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Burning sensation	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Clonus	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Cognitive disorder	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Extrapyramidal disorder	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Facial paresis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Lethargy	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Migraine	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Paraesthesia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Radiculitis lumbosacral	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Sciatica	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Somnolence	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Nervous system disorders Tremor	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Diarrhoea	3.4% 5/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	1.5% 2/133 • Upto Week 24. Safety population was used for analysis.	2.0% 3/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Nausea	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	3.3% 5/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Abdominal pain upper	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Constipation	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Vomiting	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Abdominal discomfort	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Abdominal pain	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Dyspepsia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Flatulence	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Pancreatitis chronic	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Gastrointestinal disorders Tongue cyst	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Insomnia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	3.3% 5/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Agitation	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	1.5% 2/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Hallucination	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Nightmare	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	2.0% 3/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Sleep disorder	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Abnormal dreams	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Depression	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Confusional state	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Delirium	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Delusion of replacement	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Depressed mood	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Hallucination, visual	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Libido increased	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Restlessness	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Psychiatric disorders Stress	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Metabolism and nutrition disorders Hyperglycaemia	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	2.1% 3/145 • Upto Week 24. Safety population was used for analysis.	1.5% 2/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Metabolism and nutrition disorders Increased appetite	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Metabolism and nutrition disorders Diabetes mellitus	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Metabolism and nutrition disorders Hypercholesterolaemia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	1.5% 2/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Metabolism and nutrition disorders Type 2 diabetes mellitus	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
General disorders Asthenia	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
General disorders Application site rash	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
General disorders Chest pain	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
General disorders Fatigue	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
General disorders Gait disturbance	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
General disorders Influenza like illness	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
General disorders Irritability	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
General disorders Malaise	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
General disorders Non-cardiac chest pain	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
General disorders Oedema peripheral	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Fall	2.1% 3/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	1.5% 2/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Contusion	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Animal bite	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Animal scratch	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Arthropod bite	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Dislocation of vertebra	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Periorbital haematoma	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Skin injury	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Back pain	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	2.0% 3/151 • Upto Week 24. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Arthralgia	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Muscle spasms	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	1.3% 2/151 • Upto Week 24. Safety population was used for analysis.
Musculoskeletal and connective tissue disorders Systemic lupus erythematosus	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Pruritus	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Dermatitis allergic	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Dermatitis contact	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Eczema	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Erythema	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Pemphigoid	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Photodermatosis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Photosensitivity reaction	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Rash	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Rash pruritic	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Skin irritation	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Skin and subcutaneous tissue disorders Skin nodule	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Vascular disorders Hypertension	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	2.6% 4/151 • Upto Week 24. Safety population was used for analysis.
Vascular disorders Haematoma	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Vascular disorders Hypertensive crisis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Vascular disorders Hypotension	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Vascular disorders Orthostatic hypotension	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Investigations Blood creatinine increased	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Investigations Blood glucose increased	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Investigations Blood potassium increased	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Investigations Blood pressure increased	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Investigations Red blood cells urine	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Investigations Urine albumin/creatinine ratio increased	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Investigations Weight decreased	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Cardiac disorders Atrial fibrillation	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Cardiac disorders Palpitations	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Cardiac disorders Sinus bradycardia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Cardiac disorders Ventricular extrasystoles	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Renal and urinary disorders Haematuria	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Renal and urinary disorders Dysuria	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Renal and urinary disorders Pollakiuria	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Renal and urinary disorders Urinary incontinence	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders Postnasal drip	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Eye disorders Conjunctivitis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	1.4% 2/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Eye disorders Angle closure glaucoma	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Eye disorders Retinal infarction	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Reproductive system and breast disorders Benign prostatic hyperplasia	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Reproductive system and breast disorders Breast mass	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Reproductive system and breast disorders Cystocele	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Hepatobiliary disorders Cholelithiasis	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Hepatobiliary disorders Hepatic steatosis	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Immune system disorders Drug hypersensitivity	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Immune system disorders Seasonal allergy	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Ear and labyrinth disorders Cerumen impaction	0.69% 1/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.
Endocrine disorders Hyperparathyroidism	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/133 • Upto Week 24. Safety population was used for analysis.	0.66% 1/151 • Upto Week 24. Safety population was used for analysis.
Surgical and medical procedures Hip arthroplasty	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.00% 0/145 • Upto Week 24. Safety population was used for analysis.	0.75% 1/133 • Upto Week 24. Safety population was used for analysis.	0.00% 0/151 • Upto Week 24. Safety population was used for analysis.

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER