Trial Outcomes & Findings for A Study of SB-742457, Added to Donepezil for the Treatment of Mild-to-moderate Alzheimer's Disease (NCT NCT00710684)

NCT ID: NCT00710684

Last Updated: 2017-12-07

Results Overview

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

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 682 participants
• Primary outcome timeframe: Baseline(Week 0) and Week 24
• Results posted on: 2017-12-07

Participant Flow

A total of 684 participants were randomized from 100 centers i.e. Australia, Argentina, Chile, Canada, United States of America, Czech Republic, Spain, Italy, Germany between 01 July 2008 and 16 November 2010.

Out of 1132 participants screened, 725 entered into 4-week placebo run-in period out of which 41 participants were placebo run-in failures. Out of 684 participants randomized, 682 were included in safety population (1 participant each from Donepezil+Placebo and Donepezil+SB742457 35 milligram [mg] group failed to take a dose of study medication).

Participant milestones

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

Reasons for withdrawal

Measure	Donepezil + Placebo Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Overall Study Adverse Event	11	19	16
Overall Study Lack of Efficacy	4	3	5
Overall Study Protocol Violation	5	5	5
Overall Study Lost to Follow-up	4	6	7
Overall Study Physician Decision	0	2	4
Overall Study Withdrawal by Subject	24	18	11
Overall Study Missing	1	0	0
Overall Study Did not continue after week 24	25	21	16

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Donepezil + Placebo n=223 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=218 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Total n=677 Participants Total of all reporting groups
Age, Continuous	73.1 years STANDARD_DEVIATION 7.49 • n=5 Participants	74.2 years STANDARD_DEVIATION 6.82 • n=7 Participants	73.8 years STANDARD_DEVIATION 6.92 • n=5 Participants	73.7 years STANDARD_DEVIATION 7.09 • n=4 Participants
Sex: Female, Male Female	129 Participants n=5 Participants	118 Participants n=7 Participants	148 Participants n=5 Participants	395 Participants n=4 Participants
Sex: Female, Male Male	94 Participants n=5 Participants	100 Participants n=7 Participants	88 Participants n=5 Participants	282 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) White	223 Participants n=5 Participants	215 Participants n=7 Participants	233 Participants n=5 Participants	671 Participants n=4 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
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline(Week 0) and Week 24

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

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

Outcome measures

Measure	Donepezil + Placebo n=193 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=184 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=200 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog) Total Score at Week 24	1.2 Score on scale Standard Error 0.45	0.5 Score on scale Standard Error 0.44	-0.4 Score on scale Standard Error 0.41	—

PRIMARY outcome

Timeframe: Baseline(Week 0) and Week 24

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

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

Outcome measures

Measure	Donepezil + Placebo n=191 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=184 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=200 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score at Week 24	0.9 Score on scale Standard Error 0.13	0.8 Score on scale Standard Error 0.13	0.7 Score on scale Standard Error 0.11	—

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24

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

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

Outcome measures

Measure	Donepezil + Placebo n=190 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=176 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=193 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Total Score at Week 24	-3.6 Score on scale Standard Error 1.18	-5.9 Score on scale Standard Error 1.29	-4.0 Score on scale Standard Error 1.09	—

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12, 36 and 48

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

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

Outcome measures

Measure	Donepezil + Placebo n=223 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=218 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48 Week 12	0.4 Score on scale Standard Error 0.33	0.1 Score on scale Standard Error 0.37	-0.9 Score on scale Standard Error 0.34	—
Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48 Week 36	2.1 Score on scale Standard Error 0.45	2.1 Score on scale Standard Error 0.48	0.9 Score on scale Standard Error 0.45	—
Change From Baseline in ADAS-Cog Total Score at Week 12, 36 and 48 Week 48	3.4 Score on scale Standard Error 0.52	3.4 Score on scale Standard Error 0.60	1.8 Score on scale Standard Error 0.50	—

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12, 36, 48

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

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

Outcome measures

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

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 12, 36 and 48

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

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

Outcome measures

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

SECONDARY outcome

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

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

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

Outcome measures

Measure	Donepezil + Placebo n=223 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=218 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48 Week 36	-3.7 Score on scale Standard Error 0.67	-3.8 Score on scale Standard Error 0.80	-1.8 Score on scale Standard Error 0.65	—
Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48 Week 12	-1.4 Score on scale Standard Error 0.57	-0.8 Score on scale Standard Error 0.49	0.3 Score on scale Standard Error 0.47	—
Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48 Week 24	-3.4 Score on scale Standard Error 0.66	-1.9 Score on scale Standard Error 0.61	-1.4 Score on scale Standard Error 0.60	—
Change From Baseline in Alzheimer's Disease Co-operative Study Group - Activities of Daily Living Inventory (ADCS- ADL) Total Score at Weeks 12, 24, 36 and 48 Week 48	-5.5 Score on scale Standard Error 0.85	-5.0 Score on scale Standard Error 0.87	-3.5 Score on scale Standard Error 0.76	—

SECONDARY outcome

Timeframe: Baseline (Week 0) and Week 24 and 48

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

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

Outcome measures

Measure	Donepezil + Placebo n=223 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=218 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48 Week 24	-0.4 Score on scale Standard Error 0.21	-0.3 Score on scale Standard Error 0.23	0.1 Score on scale Standard Error 0.21	—
Change From Baseline in Mini Mental State Examination (MMSE) Total Score at Week 24 and 48 Week 48	-1.1 Score on scale Standard Error 0.28	-1.3 Score on scale Standard Error 0.33	-0.7 Score on scale Standard Error 0.27	—

SECONDARY outcome

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

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

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

Outcome measures

Measure	Donepezil + Placebo n=225 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=221 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase Any AE	125 Participants	137 Participants	146 Participants	—
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) During Treatment Phase Any SAE	17 Participants	26 Participants	27 Participants	—

SECONDARY outcome

Timeframe: Up to Week 48

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

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

Outcome measures

Measure	Donepezil + Placebo n=225 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=221 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Number of Participants With Parameters of Clinical Concern - Hematology Lymphocytes, low	6 Participants	5 Participants	7 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology MCH, low	0 Participants	1 Participants	0 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology WBC, high	0 Participants	3 Participants	2 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Eosinophils, high	1 Participants	0 Participants	4 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Hematocrit, low	2 Participants	2 Participants	1 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Hematocrit, high	0 Participants	1 Participants	0 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Hemoglobin, low	5 Participants	3 Participants	8 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Hemoglobin, high	3 Participants	1 Participants	0 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Lymphocytes, high	0 Participants	2 Participants	1 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology MCV, low	0 Participants	1 Participants	0 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Monocytes, low	35 Participants	32 Participants	32 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Monocytes, high	0 Participants	1 Participants	0 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Neutrophil bands, high	0 Participants	1 Participants	1 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Platelet count, low	1 Participants	4 Participants	3 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Platelet count, high	2 Participants	3 Participants	5 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Segmented Neutrophils, low	7 Participants	3 Participants	7 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Segmented Neutrophils, high	3 Participants	4 Participants	5 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Total Neutrophils, low	7 Participants	3 Participants	7 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology Total Neutrophils, high	0 Participants	3 Participants	2 Participants	—
Number of Participants With Parameters of Clinical Concern - Hematology WBC, low	4 Participants	1 Participants	5 Participants	—

SECONDARY outcome

Timeframe: Up to Week 48

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

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

Outcome measures

Measure	Donepezil + Placebo n=225 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=221 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Magnesium, low	0 Participants	1 Participants	0 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Phosphorus, inorganic, high	0 Participants	0 Participants	1 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Potassium, high	2 Participants	10 Participants	9 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry ALT, high	2 Participants	4 Participants	4 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Alkaline Phosphatase, high	5 Participants	6 Participants	4 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry ASAT, high	2 Participants	7 Participants	4 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry BUN/Creatinine ratio, high	11 Participants	7 Participants	5 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Calcium, low	0 Participants	0 Participants	1 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Carbon dioxide content/Bicarbonate, low	3 Participants	2 Participants	2 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Cholesterol, high	11 Participants	4 Participants	7 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Creatine Kinase, high	5 Participants	2 Participants	6 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Creatinine, high	3 Participants	3 Participants	5 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Direct Bilirubin, high	2 Participants	1 Participants	1 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry GGT, high	5 Participants	7 Participants	7 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Glucose, low	17 Participants	24 Participants	13 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Glucose, high	54 Participants	42 Participants	54 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry HDL Cholesterol, direct, low	3 Participants	0 Participants	2 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry LDL Cholesterol, high	35 Participants	29 Participants	40 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Sodium, high	0 Participants	1 Participants	1 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Total Bilirubin, high	2 Participants	1 Participants	1 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Triglycerides, high	1 Participants	0 Participants	0 Participants	—
Number of Participants With Parameters of Clinical Concern - Clinical Chemistry Urea/BUN, high	17 Participants	12 Participants	25 Participants	—

SECONDARY outcome

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

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

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

Outcome measures

Measure	Donepezil + Placebo n=215 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=233 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Exposure Estimates for SB-742457 : Area Under the Concentration Time Curve Over the Dosing Interval at Steady State (AUCτss)	1640.76 Nanogram hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 35.96	4160.29 Nanogram hour per milliliter (ng*h/mL) Geometric Coefficient of Variation 31.67	—	—

SECONDARY outcome

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

Population: PK population.

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

Outcome measures

Measure	Donepezil + Placebo n=215 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=233 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Exposure Estimates for SB-742457 : Minimum Concentrations at Steady State (Cmin-ss)	53.42 ng/mL Geometric Coefficient of Variation 38.58	135.05 ng/mL Geometric Coefficient of Variation 33.08	—	—

SECONDARY outcome

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

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

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

Outcome measures

Measure	Donepezil + Placebo n=179 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=1 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=484 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg n=1 Participants Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Exposure Estimates for Donepezil (Cavgss)	20.72 ng/mL Geometric Coefficient of Variation 45.07	17.68 ng/mL Geometric Coefficient of Variation NA Only one participant was analyzed, hence, dispersion value could not be generated.	39.79 ng/mL Geometric Coefficient of Variation 46.62	36.60 ng/mL Geometric Coefficient of Variation NA Only one participant was analyzed.

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 24 and Week 48

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

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

Outcome measures

Measure	Donepezil + Placebo n=206 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=202 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=219 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene Week 24	1.9 Score on scale Standard Deviation 5.58	1.0 Score on scale Standard Deviation 6.63	-0.1 Score on scale Standard Deviation 5.40	—
Change From Baseline in ADAS-Cog Scale in Participants With APOE4 Gene Week 48	4.7 Score on scale Standard Deviation 6.52	4.2 Score on scale Standard Deviation 7.46	1.8 Score on scale Standard Deviation 5.72	—

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 24 and Week 48

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

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

Outcome measures

Measure	Donepezil + Placebo n=206 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=202 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=219 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene Week 24	1.1 Score on scale Standard Deviation 2.02	0.6 Score on scale Standard Deviation 1.59	0.8 Score on scale Standard Deviation 1.47	—
Change From Baseline in CDR-SB Scale in Participants With APOE4 Gene Week 48	1.8 Score on scale Standard Deviation 1.98	1.5 Score on scale Standard Deviation 2.11	1.4 Score on scale Standard Deviation 1.92	—

SECONDARY outcome

Timeframe: Baseline (Week 0) to Week 24 and Week 48

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

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

Outcome measures

Measure	Donepezil + Placebo n=206 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=202 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=219 Participants Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil 15 mg Participants received a stable dose of donepezil 15 mg at least for 6 months and a stable regimen for at least 2 months. The participants received SB742457 15 mg or 35 mg or placebo matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy.
Change From Baseline in RBANS Scale in Participants With APOE4 Gene Week 24	-5.2 Score on scale Standard Deviation 14.30	-6.0 Score on scale Standard Deviation 20.07	-6.0 Score on scale Standard Deviation 14.84	—
Change From Baseline in RBANS Scale in Participants With APOE4 Gene Week 48	-7.7 Score on scale Standard Deviation 16.46	-11.3 Score on scale Standard Deviation 16.13	-5.9 Score on scale Standard Deviation 14.04	—

Adverse Events

Donepezil + Placebo

Serious events: 17 serious events

Other events: 41 other events

Deaths: 1 deaths

Donepezil + SB-742457 15 mg

Serious events: 26 serious events

Other events: 32 other events

Deaths: 5 deaths

Donepezil + SB-742457 35 mg

Serious events: 27 serious events

Other events: 33 other events

Deaths: 4 deaths

Serious adverse events

Measure	Donepezil + Placebo n=225 participants at risk Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=221 participants at risk Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 participants at risk Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Nervous system disorders Cerebrovascular accident	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	1.4% 3/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Syncope	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.85% 2/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Cerebral haemorrhage	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.90% 2/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Aphasia	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Dementia Alzheimer's type	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Dizziness	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Epilepsy	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Loss of consciousness	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Psychomotor hyperactivity	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Sciatica	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Nervous system disorders Transient ischaemic attack	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Pneumonia	1.3% 3/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	1.3% 3/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Urinary tract infection	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Abdominal abscess	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Bronchopneumonia	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Diverticulitis	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Erysipelas	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Influenza	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Respiratory tract infection	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Skin infection	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Fall	0.89% 2/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Humerus fracture	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Femur fracture	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Hand fracture	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Hip fracture	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Joint dislocation	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Lower limb fracture	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Post procedural haemorrhage	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Radius fracture	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Skin laceration	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Skull fracture	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Splenic injury	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Cardiac disorders Bradycardia	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Cardiac disorders Adams-Stokes syndrome	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Cardiac disorders Angina pectoris	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Cardiac disorders Arteriosclerosis coronary artery	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Cardiac disorders Cardiac failure	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Cardiac disorders Cardio-respiratory arrest	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Cardiac disorders Sick sinus syndrome	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Gastrointestinal disorders Colonic polyp	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Gastrointestinal disorders Diarrhoea	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Gastrointestinal disorders Diverticulum	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Gastrointestinal disorders Dyspepsia	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Gastrointestinal disorders Oesophageal obstruction	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Gastrointestinal disorders Vomiting	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Gastric cancer	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Glioblastoma	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Oesophageal carcinoma	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Penile neoplasm	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
General disorders Death	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
General disorders Fatigue	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
General disorders Pyrexia	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Metabolism and nutrition disorders Dehydration	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Metabolism and nutrition disorders Decreased appetite	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Respiratory, thoracic and mediastinal disorders Dyspnoea	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Respiratory, thoracic and mediastinal disorders Epistaxis	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Vascular disorders Circulatory collapse	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Vascular disorders Deep vein thrombosis	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Vascular disorders Haematoma	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Ear and labyrinth disorders Vertigo	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.85% 2/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Psychiatric disorders Confusional state	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Psychiatric disorders Disorientation	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Hepatobiliary disorders Biliary colic	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Musculoskeletal and connective tissue disorders Neck pain	0.44% 1/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Renal and urinary disorders Urethral stenosis	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.45% 1/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Reproductive system and breast disorders Metrorrhagia	0.00% 0/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.00% 0/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	0.42% 1/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.

Other adverse events

Measure	Donepezil + Placebo n=225 participants at risk Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received placebo tablets matching with SB742457 orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 15 mg n=221 participants at risk Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 15 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.	Donepezil + SB-742457 35 mg n=236 participants at risk Eligible participants who were on donepezil (at least 6 months and a stable regimen for at least 2 months) received SB742457 35 mg orally once daily for a treatment period of 48 weeks as an adjunct treatment to stable donepezil therapy. At the end of 24 weeks treatment participants were asked to consent/assent to continue their randomized treatment for a further 24 weeks.
Infections and infestations Nasopharyngitis	7.6% 17/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	8.6% 19/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	7.6% 18/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Infections and infestations Urinary tract infection	6.7% 15/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	4.5% 10/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	5.5% 13/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.
Injury, poisoning and procedural complications Fall	5.3% 12/225 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	1.8% 4/221 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.	2.1% 5/236 • AE data was collected up to follow-up i.e. 2 weeks post end of treatment Up to follow-up i.e. 2 weeks post end of treatment (Week 24, Week 48 or Early Withdrawal). Safety population consisted of all participants randomized to treatment who had received at least one dose of study medication. Safety population was used for the analysis of SAE and nSAE.

Additional Information

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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