A 24-Month Study to Evaluate the Efficacy and Safety of Elenbecestat (E2609) in Participants With Early Alzheimer's Disease

The clinical dementia rating (CDR) scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in mixed effects model for repeated measures (MMRM) who were evaluable for this specific outcome measure.

A TEAE is defined as an adverse event that emerged during treatment or within 28 days following the last dose of study drug, having been absent at pretreatment (Baseline) or reemerged during treatment, having been present at pretreatment (Baseline) but stopped before treatment, or worsened in severity during treatment relative to the pretreatment state, when the adverse event was continuous. Number of participants with TEAEs (serious and non-serious adverse events) were reported based on their safety assessments of laboratory tests, suicidal ideation and suicidal behavior, drug abuse potential, physical examination, neurological examination, regular measurement of vital signs, magnetic resonance imaging and electrocardiogram parameter values.

Time frame: From first dose of study drug up to approximately 6 months (including 1 month follow up) for the extension phase

Population: All safety participants was the group of participants who enrolled into the extension phase and received at least 1 dose of study drug in the extension phase.

ADCOMS is a weighted linear combination of 12 items from three existing clinical scales: the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), the Mini Mental State Examination (MMSE), and the CDR. Four items are from the ADAS-cog (A4 \[Delayed Word Recall\], A7 \[Orientation\], A8 \[Word Recognition\], A11 \[Word Finding\]); 2 items are from the MMSE (M1 \[Orientation Time\], M7 \[Drawing\]); 6 items are from the CDR (C1 \[Personal Care\], C2 \[Community Affairs\], C3 \[Home and Hobbies\], C4 \[Judgment and Problem Solving\], C5 \[Memory\], C6 \[Orientation\]). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score indicates worse performance.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

Amyloid PET scan assesses cerebral amyloid load using 3 tracers (florbetapir, florbetaben and flutemetamol) which is standardized into centiloids for evaluation of AD. Centiloid values on centiloid scale is based on mean composite SUVR in cingulate, frontal, parietal and temporal cortexes using whole cerebellum as reference region. SUVR is ratio of tracer uptake in each of cingulate, frontal, parietal and temporal cortexes relative to cerebellum. The centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The pharmacodynamic (PD) analysis set was the group of participants in the core phase who had sufficient PD data to derive at least 1 PD parameter. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

The ADAS-cog14 Word List is a summation of two items: Immediate Word-recall and Delayed Word-recall. Immediate Word-recall test: Participants are asked to recall words and the number of No responses for each trial (total 3 trials) are summed. Subscore: sum of scores from 3 trials, divided by 3. Score ranges from 0 to 10. Delayed Word-recall: Participants used to recall words after a delay and the number of No responses are summed. Score ranges from 0 to 10. The Total Score ranges from 0 to 20. Higher score indicates more impairment.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

ADCOMS is a weighted linear combination of 12 items from three existing clinical scales: the ADAS-cog, the MMSE, and the CDR. Four items are from the ADAS-cog (A4 \[Delayed Word Recall\], A7 \[Orientation\], A8 \[Word Recognition\], A11 \[Word Finding\]); 2 items are from the MMSE (M1 \[Orientation Time\], M7 \[Drawing\]); 6 items are from the CDR (C1 \[Personal Care\], C2 \[Community Affairs\], C3 \[Home and Hobbies\], C4 \[Judgment and Problem Solving\], C5 \[Memory\], C6 \[Orientation\]). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score indicates worse performance. Amyloid PET scans allow in vivo assessment of cerebral amyloid load. SUVR indicates the ratio of tracer uptake in the frontal cortex relative to the cerebellum or the ratio of tracer uptake in the whole brain relative to the cerebellum.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

ADAS-cog11 is a psychometric instrument that evaluates 11-items (Immediate Word-recall \[0 to 10\], Commands \[0-5\], Constructional Praxis \[0-5\], Naming Objects/Fingers \[0-5\], Ideational Praxis \[0-5\], Orientation\[0-8\], Word Recognition \[0-12\], Remembering Test Instructions \[0-5\], Comprehension\[0-5\], Word Finding Difficulty \[0-5\], Spoken Language Ability \[0-5\] test) and is considered more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The Total score ranges from 0 to 70. Higher score indicates more impairment.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

ADAS-cog14 is a psychometric instrument that evaluates 14-items (Immediate Word-recall \[0-10\], Commands \[0-5\], Constructional Praxis \[0-5\], Delayed Word-recall \[0-10\], Naming Objects/Fingers \[0-5\], Ideational Praxis \[0-5\], Orientation\[0-8\], Word Recognition \[0-12\], Remembering Test Instructions \[0-5\], Comprehension\[0-5\], Word Finding Difficulty \[0-5\], Spoken Language Ability \[0-5\], Executive Function \[0-5\], and Number Cancellation \[0-5\] test). It is considered to be more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The total score ranges from 0 to 90. Higher score indicates more impairment.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment. Amyloid PET scans allow in vivo assessment of cerebral amyloid load. SUVR indicates the ratio of tracer uptake in the frontal cortex relative to the cerebellum or the ratio of tracer uptake in the whole brain relative to the cerebellum.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

FAQ scores 10 items & measures activities of daily living (paying bills/balancing checkbook, assembling tax records, shopping alone for clothes or groceries, playing game of skill such as bridge or chess/working on a hobby, heating water & turning off stove, preparing balanced meal, keeping track of current events, paying attention & understanding television program, remembering appointments, driving or traveling out of neighborhood). Each item is rated as follows: 0=Normal, 1=Has difficulty but does by self, 2=Requires assistance, 3=Dependent, or 8=Not Applicable. The total score is the sum of all 10 items & ranges from 0 to 30. Higher score indicates more impairment. If any activity was missed, then the total score was missed. Activities rated as Not Applicable were not used in the computation of the total score. To account for Not Applicable activity, the total score was weighted as:Total Score=Total Score\*30/(30 minus 3 times the number of activities markedNot Applicable).

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

The MMSE is a cognitive instrument commonly used for screening purposes, for staging of disease severity and is often measured longitudinally in AD clinical studies to follow disease progression and treatment effects. MMSE is composed of 30 questions grouped into domains (Orientation to Time \[0-5\], Orientation to Place \[0-5\], Registration \[0-3\], Attention and Calculation \[0-5\], Recall \[0-3\], Naming \[0-2\], Repetition \[0-1\], Comprehension \[0-3\], Reading \[0-1\], Writing \[0-1\], Drawing \[0-1\]). For each of the MMSE domains, six items are computed (Orientation to Time \[0-5\], Orientation to Place \[0-5\], Registration \[0-3\], Attention and Calculation \[0-5\], Recall \[0-3\], Language: Naming, Repetition, Comprehension, Reading, Writing, and Drawing \[0-9\]). The MMSE Total Score is the sum of the six domains and ranges from 0 to 30. If any domain score was missing then the total score was missing. Higher score indicates better function.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies all participants included in MMRM who were evaluable for this specific outcome measure.

ADAS-cog11 is a psychometric instrument that evaluates 11-items (Immediate Word-recall \[0 to 10\], Commands \[0-5\], Constructional Praxis \[0-5\], Naming Objects/Fingers \[0-5\], Ideational Praxis \[0-5\], Orientation\[0-8\], Word Recognition \[0-12\], Remembering Test Instructions \[0-5\], Comprehension\[0-5\], Word Finding Difficulty \[0-5\], Spoken Language Ability \[0-5\] test) and is considered more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The Total score ranges from 0 to 70. Higher score indicates more impairment.

Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

ADAS-cog14 is a psychometric instrument that evaluates 14-items (Immediate Word-recall \[0 to 10\], Commands \[0-5\], Constructional Praxis \[0-5\], Delayed Word-recall \[0-10\], Naming Objects/Fingers \[0-5\], Ideational Praxis \[0-5\], Orientation\[0-8\], Word Recognition \[0-12\], Remembering Test Instructions \[0-5\], Comprehension\[0-5\], Word Finding Difficulty \[0-5\], Spoken Language Ability \[0-5\], Executive Function \[0-5\], and Number Cancellation \[0-5\] test). It is considered to be more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The Total Score ranges from 0 to 90. Higher score indicates more impairment.

Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

The ADAS-cog14 Word List is a summation of two items: Immediate Word-recall and Delayed Word-recall. Immediate Word-recall test: Participants are asked to recall words and the number of No responses for each trial (total 3 trials) are summed. Subscore: sum of scores from 3 trials, divided by 3. Score ranges from 0 to 10. Delayed Word-recall: Participants used to recall words after a delay and the number of No responses are summed. Score ranges from 0 to 10. The Total Score ranges from 0 to 20. Higher score indicates more impairment.

Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

ADCOMS is a weighted linear combination of 12 items from three existing clinical scales: the ADAS-cog, the MMSE, and the CDR. Four items are from the ADAS-cog (A4 \[Delayed Word Recall\], A7 \[Orientation\], A8 \[Word Recognition\], A11 \[Word Finding\]); 2 items are from the MMSE (M1 \[Orientation Time\], M7 \[Drawing\]); 6 items are from the CDR (C1 \[Personal Care\], C2 \[Community Affairs\], C3 \[Home and Hobbies\], C4 \[Judgment and Problem Solving\], C5 \[Memory\], C6 \[Orientation\]). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score indicates worse performance.

Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment.

Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow up (up to Month 27)

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

The MMSE is a cognitive instrument commonly used for screening purposes, for staging of disease severity and is often measured longitudinally in AD clinical studies to follow disease progression and treatment effects. MMSE is composed of 30 questions grouped into domains (Orientation to Time \[0-5\], Orientation to Place \[0-5\], Registration \[0-3\], Attention and Calculation \[0-5\], Recall \[0-3\], Naming \[0-2\], Repetition \[0-1\], Comprehension \[0-3\], Reading \[0-1\], Writing \[0-1\], Drawing \[0-1\]). For each of the MMSE domains, six items are computed (Orientation to Time \[0-5\], Orientation to Place \[0-5\], Registration \[0-3\], Attention and Calculation \[0-5\], Recall \[0-3\], Language: Naming, Repetition, Comprehension, Reading, Writing, and Drawing \[0-9\]). The MMSE Total Score is the sum of the six domains and ranges from 0 to 30. If any domain score was missing then the total score was missing. Higher score indicates better function.

Time frame: From last dose in the core phase (up to Month 24) up to 3 months follow-up (up to Month 27)

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment. In this outcome measure, change per year (mean slope) in CDR-SB score was calculated up to month 24, where higher change indicated more impairment and lower change indicated less impairment.

Time frame: Up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement.

Time (in months) to conversion to dementia for participants who were not clinically staged as having dementia at the core phase baseline (that is time from randomization to conversion to dementia in clinical diagnosis).

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement. Here overall number of participants analyzed signifies participants who were evaluable for this outcome measure.

The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The global CDR score is computed via an algorithm and ranges from 0 to 3. Higher score indicates more impairment. In this outcome measure, time (in months) to worsening of CDR score (that is, an increase from baseline by at least 0.5 points on the global CDR scale on 2 consecutive scheduled visits) up to month 24 was calculated.

Time frame: Up to Month 24 of the core phase

Population: The FAS was the group of randomized participants who received at least 1 dose of study drug in the core phase and had baseline and at least 1 post-dose primary efficacy measurement.

ADAS-cog14 is a psychometric instrument that evaluates 14-items (Immediate Word-recall \[0 to 10\], Commands \[0-5\], Constructional Praxis \[0-5\], Delayed Word-recall \[0-10\], Naming Objects/Fingers \[0-5\], Ideational Praxis \[0-5\], Orientation\[0-8\], Word Recognition \[0-12\], Remembering Test Instructions \[0-5\], Comprehension\[0-5\], Word Finding Difficulty \[0-5\], Spoken Language Ability \[0-5\], Executive Function \[0-5\], and Number Cancellation \[0-5\] test). It is considered to be more sensitive for less impaired populations such as MCI/Prodromal and mild AD participants. The total score ranges from 0 to 90. Higher score indicates more impairment.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

Population: Data could not be reported as the study was terminated prior to reaching the specified time point for assessment in the extension phase. Statistical analysis plan was modified to indicate that the extension phase analysis was not done.

The ADAS-cog14 Word List is a summation of two items: Immediate Word-recall and Delayed Word-recall. Immediate Word-recall test: Participants are asked to recall words and the number of No responses for each trial (total 3 trials) are summed. Subscore: sum of scores from 3 trials, divided by 3. Score ranges from 0 to 10. Delayed Word-recall: Participants used to recall words after a delay and the number of No responses are summed. Score ranges from 0 to 10. The Total Score ranges from 0 to 20. Higher score indicates more impairment.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

Population: Data could not be reported as the study was terminated prior to reaching the specified time point for assessment in the extension phase. Statistical analysis plan was modified to indicate that the extension phase analysis was not done.

ADCOMS is a weighted linear combination of 12 items from three existing clinical scales: the ADAS-cog, the MMSE, and the CDR. Four items are from the ADAS-cog (A4 \[Delayed Word Recall\], A7 \[Orientation\], A8 \[Word Recognition\], A11 \[Word Finding\]); 2 items are from the MMSE (M1 \[Orientation Time\], M7 \[Drawing\]); 6 items are from the CDR (C1 \[Personal Care\], C2 \[Community Affairs\], C3 \[Home and Hobbies\], C4 \[Judgment and Problem Solving\], C5 \[Memory\], C6 \[Orientation\]). Composite score is derived from the variables from the 12 items, and ranges from 0 to 1.97, where higher score indicates worse performance.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

Population: Data could not be reported as the study was terminated prior to reaching the specified time point for assessment in the extension phase. Statistical analysis plan was modified to indicate that the extension phase analysis was not done.

The CDR scale is a clinical global rating scale that requires interviewing both the participant and an informant who knows and has contact with the participant. The CDR scale is a clinician directed assessment of both cognition and function, and is intended to capture the state and therefore the disease stage of the participant. The CDR scale assesses 6 domains of participant function (memory, orientation, judgement and problem solving, community affairs, home and hobbies and personal care) on a 5-point scale in which no impairment=0, questionable impairment=0.5, mild impairment=1, moderate impairment=2 and severe impairment=3. The CDR-SB is a sum of the individual domain scores and ranges from 0 to 18. Higher score indicates more impairment.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

Population: Data could not be reported as the study was terminated prior to reaching the specified time point for assessment in the extension phase. Statistical analysis plan was modified to indicate that the extension phase analysis was not done.

FAQ scores 10 items & measures activities of daily living (paying bills/balancing checkbook, assembling tax records, shopping alone for clothes or groceries, playing game of skill such as bridge or chess/working on a hobby, heating water & turning off stove, preparing balanced meal, keeping track of current events, paying attention & understanding television program, remembering appointments, driving or traveling out of neighborhood). Each item is rated as follows: 0=Normal, 1=Has difficulty but does by self, 2=Requires assistance, 3=Dependent, or 8=Not Applicable. The total score is the sum of all 10 items & ranges from 0 to 30. Higher score indicates more impairment. If any activity was missed, then the total score was missed. Activities rated as Not Applicable were not used in the computation of the total score. To account for Not Applicable activity, the total score was weighted as:Total Score=Total Score\*30/(30 minus 3 times the number of activities markedNot Applicable).

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

Population: Data could not be reported as the study was terminated prior to reaching the specified time point for assessment in the extension phase. Statistical analysis plan was modified to indicate that the extension phase analysis was not done.

The MMSE is a cognitive instrument commonly used for screening purposes, for staging of disease severity and is often measured longitudinally in AD clinical studies to follow disease progression and treatment effects. MMSE is composed of 30 questions grouped into domains (Orientation to Time \[0-5\], Orientation to Place \[0-5\], Registration \[0-3\], Attention and Calculation \[0-5\], Recall \[0-3\], Naming \[0-2\], Repetition \[0-1\], Comprehension \[0-3\], Reading \[0-1\], Writing \[0-1\], Drawing \[0-1\]). For each of the MMSE domains, six items are computed (Orientation to Time \[0-5\], Orientation to Place \[0-5\], Registration \[0-3\], Attention and Calculation \[0-5\], Recall \[0-3\], Language: Naming, Repetition, Comprehension, Reading, Writing, and Drawing \[0-9\]). The MMSE Total Score is the sum of the six domains and ranges from 0 to 30. If any domain score is missing then the total score is missing. Higher score indicates better function.

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

Population: Data could not be reported as the study was terminated prior to reaching the specified time point for assessment in the extension phase. Statistical analysis plan was modified to indicate that the extension phase analysis was not done.

Time (in months) to conversion to dementia for participants who were not clinically staged as having dementia at the core phase baseline (that is time from randomization to conversion to dementia in clinical diagnosis).

Time frame: Baseline (Day 1: before first dose in the core phase) up to Month 12 of the extension phase

Population: Data could not be reported as the study was terminated prior to reaching the specified time point for assessment in the extension phase. Statistical analysis plan was modified to indicate that the extension phase analysis was not done.