Dose-Finding Study To Evaluate Safety, Tolerability, and Efficacy of E2609 in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (Prodromal Alzheimer's Disease) and Mild to Moderate Dementia Due to Alzheimer's Disease

Sponsor

Eisai Inc. (Industry)

Overall Status

Terminated

CT.gov ID

NCT02322021

Collaborator

Biogen (Industry)

Enrollment

Locations

Arms

60.8

Actual Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 2 study to evaluate safety and efficacy in participants with Mild Cognitive Impairment due to Alzheimer's Disease/Prodromal Alzheimer's Disease (referred to as MCI/Prodromal) and mild to moderate dementia due to Alzheimer's Disease (referred to as mild to moderate AD). This study will have a Core Phase and an Extension Phase.

Condition or Disease	Intervention/Treatment	Phase
Alzheimer Disease Dementia, Alzheimer Type	Drug: E2609 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

A Placebo-Controlled, Double-Blind, Parallel-Group, Randomized, Proof-of-Concept, Dose-Finding Study To Evaluate Safety, Tolerability, and Efficacy of E2609 in Subjects With Mild Cognitive Impairment Due to Alzheimer's Disease (Prodromal Alzheimer's Disease) and Mild to Moderate Dementia Due to Alzheimer's Disease

Actual Study Start Date :

Nov 26, 2014

Actual Primary Completion Date :

Dec 20, 2019

Actual Study Completion Date :

Dec 20, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: MCI/Prodromal Cohort: Low Dose A low dose of E2609 will be assessed.	Drug: E2609 Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Experimental: MCI/Prodromal Cohort: Middle Dose A middle dose of E2609 will be assessed.	Drug: E2609 Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Experimental: MCI/Prodromal Cohort: High Dose A high dose of E2609 will be assessed.	Drug: E2609 Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Placebo Comparator: MCI/Prodromal Cohort: Placebo	Drug: Placebo Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Experimental: Mild to Moderate AD Cohort: Low Dose A low dose of E2609 will be assessed.	Drug: E2609 Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Experimental: Mild to Moderate AD Cohort: High Dose A high dose of E2609 will be assessed.	Drug: E2609 Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Placebo Comparator: Mild to Moderate AD Cohort: Placebo	Drug: Placebo Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.
Experimental: Mild to Moderate AD cohort: Middle Dose A middle dose of E2609 will be assessed.	Drug: E2609 Each participant will receive 2 tablets, which when combined will make up the required doses of E2609 or placebo, to be administered orally once per day (QD) with food.

Outcome Measures

Primary Outcome Measures

Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs) [Up to 21 months]
A TEAE is defined as an adverse event that emerges during treatment, having been absent at pre-treatment (Baseline) or re-emerges during treatment, having been present at pre-treatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pre-treatment state, when the adverse event is continuous.
Core Phase: Number of Participants With Serious Adverse Events (SAEs) [Up to 21 months]
A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug).
Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values [Up to 21 months]
Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values [Month 0(Baseline,Week 2,Week 3,Week 4);Month 1(Week 5,Week 7);Month 2(Week 9,Week 11);Month 3(Week 13);Month 4(Week 17);Month 5(Week 21);Month 6(Week 27);Month 9(Week 40);Month 12(Week 53);Month 15(Week 66);Month 18(Week 79) and Follow-up at Month 1 and 3]
Participants having no markedly abnormal vital sign values (no markedly abnormal high or no markedly abnormal low) in all core phase arms were not included in the data reported.
Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings [Up to 21 months]
QTcF interval means corrected QT interval (QTc) calculated using Fridericia's formula.
Extension Phase: Number of Participants With TEAEs and SAEs [Up to 34 months]
TEAE: adverse event that emerges during treatment, having been absent at pre-treatment or reemerges during treatment, having been present at pre-treatment but stopped before treatment, or worsens in severity during treatment relative to pre-treatment state. Number of participants with TEAEs were reported based on safety assessments of laboratory tests, physical examination, regular measurement of vital signs, magnetic resonance imaging and electrocardiogram parameter values. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening (immediate risk of death from adverse event, this does not include event that, had it occurred in more severe form or is allowed to continue, might have caused death); requires inpatient or prolongation of existing hospitalization; results in persistent/significant disability/incapacity; is congenital anomaly/birth defect (in child of participant exposed to drug). Number of participants with TEAEs and SAEs were reported.
Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values [Up to 34 months]
Extension Phase: Number of Participants With Markedly Abnormal ECG Findings [Up to 34 months]
QTcF interval means QTc interval calculated using Fridericia's formula.
Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values [Up to 34 months]
Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings [Up to 34 months]
Brain MRIs are collected to assess for potential drug-related changes that might have constituted a safety concern. Safety brain MRI is assessed using a standardized procedure that included fluid-attenuated inversion recovery (FLAIR), gradient-echo, T1, and diffusion-weighted sequences to determine the presence of focal lesions including, but not limited to, evidence for ischemic and hemorrhagic stroke, subdural hematoma, neoplasm, arteriovenous malformation, micro and macrohemorrhages, superficial siderosis, lacunar infarcts, white matter abnormalities, and vasogenic edema. Participants with abnormal values related to safety brain MRI were reported.

Secondary Outcome Measures

Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment [Month 1 (Week 5) and Month 18 (Week 79)]
The measurement of the amyloid proteins Abeta(1-x) and Abeta(1-42), in CSF have been shown to be important biomarkers for alzheimer's disease.
Core Phase: Mean Concentration of Elenbecestat in CSF [Month 1 (Week 5) and Month 18 (Week 79)]
Core Phase: Mean Concentration of Elenbecestat in Plasma [Month 0 (Week 3), Month 3 (Week 13), Month 6 (Week 27), Month 12 (Week 53): Pre-dose, 1 to 6 hours Post-dose; Month 1 (Week 5), Month 18 (Week 79): Pre-dose, 4 to 8 hours Post-dose]
Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores [Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32]
MMSE is a 30-point scale that measures orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. Scores ranges from 0 (most impaired) to 30 (no impairment). Lower score indicates more impairment.
Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score [Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32]
The FAQ has 10 items concerned with performing daily tasks necessary for independent living. The caregiver or informant provides performance ratings on 10 complex activities of daily living performed within the preceding 4 weeks. Score ranges from 0 (independent) to 30 (dependent). Lower score indicates that participant can live independently. Higher score indicates that participant cannot live independently.
Extension Phase: Percent Change From Extension Phase Baseline in Plasma Amyloid (A) Beta(1-x) Measurements at Months 12 and 24 [Month 12 and Month 24]
The measurement of the amyloid protein Abeta(1-x), in plasma has been shown to be an important biomarker for alzheimer's disease.
Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at Month 24 [Month 24]
Total hippocampal volume is measured by volumetric magnetic resonance imaging (vMRI). Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total hippocampal volume is calculated by summing up right and left hippocampal volumes.
Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24 [Month 24]
Left and right hippocampal volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Left and right hippocampal volumes represent a summary measure in the left and right hippocampal regions.
Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at Month 24 [Month 24]
Whole brain volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Whole brain volume represents a summary measure of total brain parenchyma which includes the cerebrum, basal ganglia, diencephalon, and cerebellum.
Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at Month 24 [Month 24]
Total Ventricular Volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total ventricular volume represents a summary measure of total including right and left lateral ventricles, third ventricle and fourth ventricle of brain.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion criteria:

Participants must meet all of the following criteria to be included in this study:

Meets the core clinical research criteria of the National Institute on Aging-Alzheimer's Association (NIA-AA) for MCI due to AD (which is consistent with Prodromal AD) or AD dementia and is 'staged' or classified as either MCI or mild to moderate dementia.
Amyloid positive Positron Emission Tomography (PET) image based on centralized PET scan reading.
Male or female, age 50 to 85 years, inclusive at time of consent.
Must have an identified caregiver or informant who is willing and able to provide follow-up information on the participant throughout the course of the study.
If receiving an Acetylcholinesterase Inhibitor (AChEI) or memantine, must have been on a stable dose for at least 12 weeks before the Baseline cognitive assessments, with no plans for dose adjustment in the foreseeable future. Treatment-naive participants can be entered into the study but there should be no plans to initiate treatment with AChEIs or memantine at the time of entry into the study.
Must have been on stable doses of all other permitted chronically used concomitant medications (that is, not related to their cognitive decline) for at least 4 weeks before randomization.

Exclusion criteria:

Participants who meet any of the following criteria will be excluded from this study:

Any neurological condition that may be contributing to cognitive impairment above and beyond that caused by the participant's AD pathology, including any co-morbidities such as cerebrovascular disease, detected by medical history, neurological examination, or magnetic resonance imaging (MRI).
History of transient ischemic attacks or stroke within 12 months of Screening.
History of epilepsy.
Evidence of depression on a rating scale at Screening or any psychiatric diagnosis or symptoms, (example, hallucinations, major depression, etc.) that could confound the diagnosis or could interfere with study assessments or procedures. This includes suicidal ideation or suicidal behavior within 6 months prior to Screening, or hospitalization or treatment for suicidal behavior in the past 5 years.
Abnormally low serum vitamin B12.
Thyroid stimulating hormone above the normal range. This applies to all participants regardless of whether or not they are taking thyroid supplements.
Participants with liver disease (hepatic impairment), at Screening or Baseline. Participant with Gilbert's syndrome need not be excluded.
Not able to have a MRI, PET scanning, or cerebrospinal fluid (CSF) collection by Lumbar Puncture (LP).
Severe visual or hearing impairment that would prevent the participant from performing psychometric tests accurately.
History of immunodeficiency disorders.
Participants with chronic viral hepatitis.
History of Tuberculosis (TB). Participants with no history of TB will be tested for previous TB exposure and a positive test will be exclusionary.
History of ophthalmic shingles or ocular Herpes Simplex Virus (HSV) infection.
Any live vaccine in the 3 months or any active infection within the last 4 weeks before study drug administration (that is, randomization).
Any chronic inflammatory disease that is not adequately controlled or requires immunosuppressive or immunomodulatory therapy.
T helper cell, cytotoxic T cell, or B cell absolute counts below normal.
Immunoglobulin (Ig) IgG, IgA, or IgM levels below normal at Screening or Baseline, unless both the Investigator and the Medical Monitor agree that the finding is not clinically significant.
Clinically significant deviation from normal in physical examination, vital signs, or clinical laboratory tests at Screening or Baseline.
Exclusionary cardiac factors include: prolonged QT interval greater than 450 millisecond from Electrocardiograms (ECGs); history of risk factors for torsade de pointes or the use of concomitant medications that prolong the QT/corrected QT interval (QTc); left bundle branch block; persistent low or high heart rate; persistent low or high blood pressure; history of cardiac arrhythmias; other clinically significant ECG abnormalities.
Type 1 or Type 2 diabetes mellitus that is not well controlled.
Malignant neoplasms within 5 years before Screening (except for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer that did not require systemic therapy; these do not exclude the participant).
Medical conditions (example, cardiac, respiratory, gastrointestinal, renal disease) that are not stably controlled, or which, in the opinion of the investigator(s), could affect the participant's safety or interfere with the study assessments.
Hypopigmentation conditions (example, albinism and vitiligo).
Known or suspected history of drug or alcohol dependency or abuse within 2 years, current use of recreational drugs or a positive urine drug test.
Planned surgery that requires general, spinal, or epidural anesthesia that would take place during the study.
Participation in any other interventional clinical study related to cognitive impairment within 6 months before Screening unless it can be documented that the participant was in a placebo treatment arm.
Currently enrolled in another clinical study or used any investigational drug or device within 60 days or 5 half-lives of the investigational medication (whichever is longer) proceeding informed consent.
Hypersensitivity to the study drug or any of the excipients or to other Beta Secretase Cleaving Enzyme (BACE) inhibitors, or to the PET tracer, or components of its formulation.
Females who are lactating or pregnant. Females of childbearing potential who do not agree to adhere to the protocol specified methods for avoiding pregnancy.
Males who do not meet the protocol requirements for avoiding their partners becoming pregnant. Sperm donation is not permitted.

Contacts and Locations

Locations

	City	State	Country
1	Bellflower	California	United States
2	Costa Mesa	California	United States
3	Glendale	California	United States
4	Irvine	California	United States
5	Aventura	Florida	United States
6	Boca Raton	Florida	United States
7	Brooksville	Florida	United States
8	Lake Worth	Florida	United States
9	Orlando	Florida	United States
10	Port Charlotte	Florida	United States
11	Atlanta	Georgia	United States
12	Savannah	Georgia	United States
13	Wichita	Kansas	United States
14	Kalamazoo	Michigan	United States
15	Mount Arlington	New Jersey	United States
16	Scotch Plains	New Jersey	United States
17	Charlotte	North Carolina	United States
18	Dayton	Ohio	United States
19	Port Royal	South Carolina	United States
20	Dallas	Texas	United States
21	San Antonio	Texas	United States

Sponsors and Collaborators

Eisai Inc.
Biogen

Investigators

None specified.

Study Documents (Full-Text)

More Information

Publications

None provided.

Responsible Party:

Eisai Inc.

ClinicalTrials.gov Identifier:

NCT02322021

Other Study ID Numbers:

E2609-G000-202
2014-002723-94

First Posted:

Dec 22, 2014

Last Update Posted:

Mar 5, 2021

Last Verified:

Mar 1, 2021

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Eisai Inc.

E2609

Mild Cognitive Impairment

Mild to Moderate Dementia

Alzheimer's Disease

Prodromal Alzheimer's Disease

Additional relevant MeSH terms:

Alzheimer Disease

Dementia

Cognitive Dysfunction

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 30 investigative sites in the United States from 26 November 2014 to 20 December 2019.
Pre-assignment Detail	A total of 444 participants were screened, of which 374 participants were screen failures and 70 participants were randomized and treated, out of which 43 participants completed the core phase and 41 participants entered the extension phase. No participant completed the extension phase. This study has Core Phase and an Extension Phase.

Arm/Group Title	Core Phase: Placebo	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to alzheimer's disease (AD)/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 milligram (mg) tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Period Title: Core Phase
STARTED	17	17	19	17	0
COMPLETED	12	9	10	12	0
NOT COMPLETED	5	8	9	5	0
Period Title: Core Phase
STARTED	0	0	0	0	41
COMPLETED	0	0	0	0	0
NOT COMPLETED	0	0	0	0	41

Baseline Characteristics

Arm/Group Title	Core Phase: Placebo	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg	Total
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Total of all reporting groups
Overall Participants	17	17	19	17	70
Age, Customized (Count of Participants)
Less than or equal to (<=) 65 years	4 23.5%	3 17.6%	2 10.5%	3 17.6%	12 17.1%
Greater than (>) 65 years	13 76.5%	14 82.4%	17 89.5%	14 82.4%	58 82.9%
Sex: Female, Male (Count of Participants)
Female	11 64.7%	9 52.9%	12 63.2%	10 58.8%	42 60%
Male	6 35.3%	8 47.1%	7 36.8%	7 41.2%	28 40%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 5.9%	0 0%	0 0%	2 11.8%	3 4.3%
Not Hispanic or Latino	16 94.1%	17 100%	19 100%	15 88.2%	67 95.7%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	2 11.8%	0 0%	2 10.5%	5 29.4%	9 12.9%
White	15 88.2%	17 100%	16 84.2%	12 70.6%	60 85.7%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	1 5.3%	0 0%	1 1.4%

Outcome Measures

1. Primary Outcome

Title	Core Phase: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description	A TEAE is defined as an adverse event that emerges during treatment, having been absent at pre-treatment (Baseline) or re-emerges during treatment, having been present at pre-treatment (Baseline) but stopped before treatment, or worsens in severity during treatment relative to the pre-treatment state, when the adverse event is continuous.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.

Arm/Group Title	Core Phase: Placebo	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.
Measure Participants	17	17	19	17
Count of Participants [Participants]	15 88.2%	15 88.2%	18 94.7%	15 88.2%

2. Primary Outcome

Title	Core Phase: Number of Participants With Serious Adverse Events (SAEs)
Description	A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening (that is, the participant is at immediate risk of death from the adverse event as it occurs, this does not include an event that, has it occurred in a more severe form or is allowed to continue, might have cause death); requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect (in the child of a participant who is exposed to the study drug).
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.

Arm/Group Title	Core Phase: Placebo	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.
Measure Participants	17	17	19	17
Count of Participants [Participants]	2 11.8%	2 11.8%	5 26.3%	1 5.9%

3. Primary Outcome

Title	Core Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
Description
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.

Arm/Group Title	Core Phase: Placebo	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.
Measure Participants	17	17	19	17
Markedly Abnormal Low: Lymphocytes	0 0%	2 11.8%	0 0%	0 0%
Markedly Abnormal Low: Leukocytes	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal Low: Neutrophils	1 5.9%	0 0%	0 0%	1 5.9%
Markedly Abnormal Low: Hemoglobin	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal Low: Calcium	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal Low: Potassium	0 0%	0 0%	1 5.3%	0 0%
Markedly Abnormal High: Potassium	2 11.8%	4 23.5%	2 10.5%	0 0%
Markedly Abnormal High: Alkaline Phosphatase	0 0%	0 0%	0 0%	1 5.9%
Markedly Abnormal High: Alanine Aminotransferase	1 5.9%	0 0%	0 0%	1 5.9%
Markedly Abnormal High: Aspartate Aminotransferase	0 0%	0 0%	0 0%	1 5.9%
Markedly Abnormal High: Gamma Glutamyl Transferase	1 5.9%	0 0%	0 0%	1 5.9%
Markedly Abnormal Low: Glucose	0 0%	1 5.9%	0 0%	0 0%
Markedly Abnormal High: Glucose	2 11.8%	4 23.5%	1 5.3%	1 5.9%
Markedly Abnormal High: Cholesterol	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal High: Triglycerides	1 5.9%	1 5.9%	3 15.8%	2 11.8%
Markedly Abnormal High: Creatinine	0 0%	2 11.8%	0 0%	0 0%

4. Primary Outcome

Title	Core Phase: Number of Participants With Markedly Abnormal Vital Sign Values
Description	Participants having no markedly abnormal vital sign values (no markedly abnormal high or no markedly abnormal low) in all core phase arms were not included in the data reported.
Time Frame	Month 0(Baseline,Week 2,Week 3,Week 4);Month 1(Week 5,Week 7);Month 2(Week 9,Week 11);Month 3(Week 13);Month 4(Week 17);Month 5(Week 21);Month 6(Week 27);Month 9(Week 40);Month 12(Week 53);Month 15(Week 66);Month 18(Week 79) and Follow-up at Month 1 and 3

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment. Here "number analyzed" signifies participants who were evaluable for this outcome measure for specific categories at given time points.

Arm/Group Title	Core Phase: Placebo	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.
Measure Participants	17	17	19	17
Markedly Abnormal Low: Temperature (Month 0: Baseline)	0 0%	2 11.8%	0 0%	2 11.8%
Markedly Abnormal Low: Temperature (Month 0: Week 2)	0 0%	0 0%	2 10.5%	2 11.8%
Markedly Abnormal Low: Temperature (Month 0: Week 3)	2 11.8%	1 5.9%	4 21.1%	0 0%
Markedly Abnormal Low: Temperature (Month 0: Week 4)	1 5.9%	3 17.6%	1 5.3%	1 5.9%
Markedly Abnormal High: Temperature (Month 0: Week 4)	0 0%	0 0%	1 5.3%	0 0%
Markedly Abnormal Low: Temperature (Month 1: Week 5)	1 5.9%	0 0%	2 10.5%	0 0%
Markedly Abnormal Low: Temperature (Month 1: Week 7)	0 0%	1 5.9%	3 15.8%	0 0%
Markedly Abnormal Low: Temperature (Month 2: Week 9)	0 0%	1 5.9%	1 5.3%	2 11.8%
Markedly Abnormal Low: Temperature (Month 2: Week 11)	1 5.9%	1 5.9%	1 5.3%	2 11.8%
Markedly Abnormal Low: Temperature (Month 3: Week 13)	1 5.9%	2 11.8%	3 15.8%	1 5.9%
Markedly Abnormal Low: Temperature (Month 4: Week 17)	1 5.9%	3 17.6%	1 5.3%	1 5.9%
Markedly Abnormal Low: Temperature (Month 5: Week 21)	1 5.9%	3 17.6%	0 0%	0 0%
Markedly Abnormal Low: Temperature (Month 6: Week 27)	0 0%	1 5.9%	0 0%	1 5.9%
Markedly Abnormal Low: Temperature (Month 9: Week 40)	1 5.9%	2 11.8%	0 0%	1 5.9%
Markedly Abnormal Low: Temperature (Month 12: Week 53)	0 0%	1 5.9%	1 5.3%	0 0%
Markedly Abnormal Low: Temperature (Month 15: Week 66)	0 0%	3 17.6%	2 10.5%	2 11.8%
Markedly Abnormal Low: Temperature (Month 18: Week 79)	0 0%	1 5.9%	0 0%	1 5.9%
Markedly Abnormal Low: Temperature (Follow-up: Month 1)	0 0%	0 0%	2 10.5%	0 0%
Markedly Abnormal Low: Temperature (Follow-up: Month 3)	0 0%	2 11.8%	4 21.1%	0 0%
Markedly Abnormal Low: Weight (Month 0: Baseline)	0 0%	0 0%	1 5.3%	0 0%
Markedly Abnormal High: Weight (Month 0: Baseline)	1 5.9%	3 17.6%	2 10.5%	1 5.9%
Markedly Abnormal High: Weight (Month 3: Week 13)	0 0%	2 11.8%	2 10.5%	2 11.8%
Markedly Abnormal High: Weight (Month 6: Week 27)	0 0%	1 5.9%	1 5.3%	1 5.9%
Markedly Abnormal High: Weight (Month 9: Week 40)	0 0%	0 0%	0 0%	1 5.9%
Markedly Abnormal High: Weight (Follow-up: Month 3)	0 0%	1 5.9%	1 5.3%	0 0%
Markedly Abnormal High: Systolic Blood Pressure (Month 0: Baseline)	0 0%	0 0%	0 0%	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 2)	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 3)	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal High: Systolic Blood Pressure (Month 0: Week 4)	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 5)	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal High: Systolic Blood Pressure (Month 1: Week 7)	0 0%	1 5.9%	0 0%	0 0%
Markedly Abnormal High: Systolic Blood Pressure (Month 3: Week 13)	0 0%	0 0%	0 0%	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure (Month 4: Week 17)	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal High: Systolic Blood Pressure (Month 6: Week 27)	0 0%	0 0%	1 5.3%	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure (Month 9: Week 40)	0 0%	0 0%	1 5.3%	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure (Month 12: Week 53)	0 0%	1 5.9%	1 5.3%	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure (Month 15: Week 66)	1 5.9%	1 5.9%	0 0%	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure (Month 18: Week 79)	0 0%	1 5.9%	1 5.3%	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 1)	1 5.9%	0 0%	1 5.3%	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure (Follow-up: Month 3)	0 0%	0 0%	0 0%	1 5.9%
Markedly Abnormal High: Diastolic Blood Pressure (Month 0: Week 3)	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal Low: Diastolic Blood Pressure (Month 0: Week 4)	1 5.9%	1 5.9%	0 0%	0 0%
Markedly Abnormal Low: Diastolic Blood Pressure (Month 1: Week 5)	0 0%	0 0%	0 0%	1 5.9%
Markedly Abnormal Low: Diastolic Blood Pressure (Month 9: Week 40)	0 0%	1 5.9%	0 0%	0 0%
Markedly Abnormal High: Diastolic Blood Pressure (Month 9: Week 40)	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 1)	1 5.9%	0 0%	0 0%	0 0%
Markedly Abnormal High: Diastolic Blood Pressure (Follow-up: Month 3)	0 0%	0 0%	0 0%	1 5.9%

5. Primary Outcome

Title	Core Phase: Number of Participants With Markedly Abnormal Electrocardiogram (ECG) Findings
Description	QTcF interval means corrected QT interval (QTc) calculated using Fridericia's formula.
Time Frame	Up to 21 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the core phase and had at least 1 post-dose safety assessment.

Arm/Group Title	Core Phase: Placebo	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.
Measure Participants	17	17	19	17
At least one post-baseline increase of >30 millisecond (msec) in QTcF interval	2 11.8%	4 23.5%	4 21.1%	2 11.8%
At least one post-baseline value of >450 msec in QTcF interval	1 5.9%	6 35.3%	4 21.1%	3 17.6%
At least one post-baseline value of >480 msec in QTcF interval	0 0%	0 0%	1 5.3%	0 0%

6. Primary Outcome

Title	Extension Phase: Number of Participants With TEAEs and SAEs
Description	TEAE: adverse event that emerges during treatment, having been absent at pre-treatment or reemerges during treatment, having been present at pre-treatment but stopped before treatment, or worsens in severity during treatment relative to pre-treatment state. Number of participants with TEAEs were reported based on safety assessments of laboratory tests, physical examination, regular measurement of vital signs, magnetic resonance imaging and electrocardiogram parameter values. SAE: any untoward medical occurrence that at any dose: results in death; is life-threatening (immediate risk of death from adverse event, this does not include event that, had it occurred in more severe form or is allowed to continue, might have caused death); requires inpatient or prolongation of existing hospitalization; results in persistent/significant disability/incapacity; is congenital anomaly/birth defect (in child of participant exposed to drug). Number of participants with TEAEs and SAEs were reported.
Time Frame	Up to 34 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	41
TEAEs	30 176.5%
SAEs	6 35.3%

7. Primary Outcome

Title	Extension Phase: Number of Participants With Markedly Abnormal Vital Sign Values
Description
Time Frame	Up to 34 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	41
Markedly Abnormal High: Diastolic Blood Pressure	1 5.9%
Markedly Abnormal Low: Diastolic Blood Pressure	1 5.9%
Markedly Abnormal High: Systolic Blood Pressure	5 29.4%
Markedly Abnormal High: Temperature	1 5.9%
Markedly Abnormal Low: Temperature	10 58.8%
Markedly Abnormal High: Weight	1 5.9%

8. Primary Outcome

Title	Extension Phase: Number of Participants With Markedly Abnormal ECG Findings
Description	QTcF interval means QTc interval calculated using Fridericia's formula.
Time Frame	Up to 34 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	41
At least one post-baseline increase of >30 msec in QTcF interval	2 11.8%
At least one post-baseline value of >450 msec in QTcF interval	4 23.5%

9. Primary Outcome

Title	Extension Phase: Number of Participants With Treatment Emergent Markedly Abnormal Laboratory Safety Test Values
Description
Time Frame	Up to 34 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	41
Markedly Abnormal Low: Lymphocytes	4 23.5%
Markedly Abnormal Low: Neutrophils	2 11.8%
Markedly Abnormal Low: Hemoglobin	1 5.9%
Markedly Abnormal High: Potassium	4 23.5%
Markedly Abnormal High: Alanine Aminotransferase	1 5.9%
Markedly Abnormal High: Gamma Glutamyl Transferase	2 11.8%
Markedly Abnormal High: Glucose	3 17.6%
Markedly Abnormal High: Triglycerides	2 11.8%
Markedly Abnormal High: Creatinine	4 23.5%
Markedly Abnormal High: Urate	1 5.9%
Markedly Abnormal Low: Platelets	1 5.9%

10. Primary Outcome

Title	Extension Phase: Number of Participants With Abnormal Magnetic Resonance Imaging (MRI) Findings
Description	Brain MRIs are collected to assess for potential drug-related changes that might have constituted a safety concern. Safety brain MRI is assessed using a standardized procedure that included fluid-attenuated inversion recovery (FLAIR), gradient-echo, T1, and diffusion-weighted sequences to determine the presence of focal lesions including, but not limited to, evidence for ischemic and hemorrhagic stroke, subdural hematoma, neoplasm, arteriovenous malformation, micro and macrohemorrhages, superficial siderosis, lacunar infarcts, white matter abnormalities, and vasogenic edema. Participants with abnormal values related to safety brain MRI were reported.
Time Frame	Up to 34 months

Outcome Measure Data

Analysis Population Description
The safety analysis set was the group of participants who received at least 1 dose of study drug in the extension phase. Here "number analyzed" signifies participants who were evaluable for this outcome measure for specific categories.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	41
Brain Vasogenic Edema	0 0%
Brain Microhemorrhages	4 23.5%
Brain White Matter Disease: Focal Lesions	25 147.1%
Brain White Matter Disease: No Lesions	2 11.8%
Area of superficial siderosis	1 5.9%
Space occupying lesion (extra axial): Meningioma	1 5.9%
Other pituitary lesion	1 5.9%

11. Secondary Outcome

Title	Core Phase: Percent Change From Baseline in Cerebrospinal Fluid (CSF) Amyloid (A) Beta(1-x) and Abeta(1-42) After 1 Month and 18 Months of Treatment
Description	The measurement of the amyloid proteins Abeta(1-x) and Abeta(1-42), in CSF have been shown to be important biomarkers for alzheimer's disease.
Time Frame	Month 1 (Week 5) and Month 18 (Week 79)

Outcome Measure Data

Analysis Population Description
The pharmacodynamic (PD) analysis set was the group of participants who had a baseline PD measurement and at least 1 post-dose PD measurement in the core phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Here "number analyzed" signifies participants who were evaluable for this outcome measure for specific categories and timepoints.

Analysis Population Description

The pharmacodynamic (PD) analysis set was the group of participants who had a baseline PD measurement and at least 1 post-dose PD measurement in the core phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Here "number analyzed" signifies participants who were evaluable for this outcome measure for specific categories and timepoints.

Arm/Group Title	Core Phase: Placebo	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.
Measure Participants	4	7	6	6
Percent Change from Baseline in CSF Abeta(1-x) at Month 1 (Week 5)	6.63 (12.545)	-18.16 (17.873)	-36.43 (16.026)	-56.66 (14.431)
Percent Change from Baseline in CSF Abeta(1-x) at Month 18 (Week 79)	-1.81 (NA)	-33.86 (11.039)	-0.71 (NA)	33.98 (160.017)
Percent Change from Baseline in CSF Abeta(1-42) at Month 1 (Week 5)	-8.53 (16.818)	-9.43 (22.798)	-20.69 (15.488)	-38.89 (16.378)
Percent Change from Baseline in CSF Abeta(1-42) at Month 18 (Week 79)	-6.50 (24.809)	-27.19 (20.172)	-24.02 (19.949)	-56.77 (5.312)

12. Secondary Outcome

Title	Core Phase: Mean Concentration of Elenbecestat in CSF
Description
Time Frame	Month 1 (Week 5) and Month 18 (Week 79)

Outcome Measure Data

Analysis Population Description
The pharmacokinetic (PK) analysis set was the group of participants with at least 1 quantifiable elenbecestat plasma concentration accompanied by a documented dosing history in the core phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Analysis Population Description

The pharmacokinetic (PK) analysis set was the group of participants with at least 1 quantifiable elenbecestat plasma concentration accompanied by a documented dosing history in the core phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Arm/Group Title	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.
Measure Participants	7	6	6
Month 1 (Week 5)	1.10 (0.438)	3.71 (1.360)	9.93 (3.568)
Month 18 (Week 79)	0.10 (0)	2.72 (3.197)	14.46 (3.411)

13. Secondary Outcome

Title	Core Phase: Mean Concentration of Elenbecestat in Plasma
Description
Time Frame	Month 0 (Week 3), Month 3 (Week 13), Month 6 (Week 27), Month 12 (Week 53): Pre-dose, 1 to 6 hours Post-dose; Month 1 (Week 5), Month 18 (Week 79): Pre-dose, 4 to 8 hours Post-dose

Outcome Measure Data

Analysis Population Description
The PK analysis set was the group of participants with at least 1 quantifiable elenbecestat plasma concentration accompanied by a documented dosing history in the core phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Analysis Population Description

The PK analysis set was the group of participants with at least 1 quantifiable elenbecestat plasma concentration accompanied by a documented dosing history in the core phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Arm/Group Title	Core Phase: Elenbecestat 5 mg Then 50 mg	Core Phase: Elenbecestat 15 mg Then 50 mg	Core Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.
Measure Participants	17	19	16
Month 0 (Week 3): Pre-dose	1.43 (1.105)	5.81 (3.785)	15.77 (11.281)
Month 0 (Week 3): 1 to 6 hours Post-dose	4.28 (3.185)	18.49 (11.272)	70.41 (37.681)
Month 1 (Week 5): Pre-dose	1.47 (0.870)	6.74 (4.246)	15.46 (10.463)
Month 1 (Week 5): 4 to 8 hours Post-dose	4.80 (2.529)	19.59 (7.940)	66.83 (21.370)
Month 3 (Week 13): Pre-dose	1.91 (1.703)	6.90 (8.126)	12.31 (7.007)
Month 3 (Week 13): 1 to 6 hours Post-dose	6.06 (2.456)	20.35 (8.893)	75.15 (27.852)
Month 6 (Week 27): Pre-dose	2.34 (2.196)	9.10 (9.018)	12.03 (8.962)
Month 6 (Week 27): 1 to 6 hours Post-dose	11.11 (15.322)	25.49 (22.247)	71.28 (39.114)
Month 12 (Week 53): Pre-dose	13.84 (18.482)	21.03 (30.897)	16.74 (22.804)
Month 12 (Week 53): 1 to 6 hours Post-dose	49.78 (40.656)	58.38 (65.148)	82.55 (56.084)
Month 18 (Week 79): Pre-dose	7.88 (5.896)	7.13 (6.990)	19.21 (13.602)
Month 18 (Week 79): 4 to 8 hours Post-dose	47.16 (28.651)	51.99 (44.656)	70.43 (22.500)

14. Secondary Outcome

Title	Extension Phase: Change From Extension Phase Baseline in the Mini-Mental State Examination (MMSE) Scores
Description	MMSE is a 30-point scale that measures orientation to time and place, registration, immediate and delayed recall, attention, language, and drawing. Scores ranges from 0 (most impaired) to 30 (no impairment). Lower score indicates more impairment.
Time Frame	Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32

Outcome Measure Data

Analysis Population Description
The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	41
Baseline	21.5 (5.67)
Change at Month 3	-0.6 (2.32)
Change at Month 6	-0.6 (2.39)
Change at Month 9	-0.9 (2.89)
Change at Month 12	-1.4 (2.43)
Change at Month 15	-1.8 (2.78)
Change at Month 18	-1.7 (3.01)
Change at Month 21	-2.5 (3.27)
Change at Month 24	-3.9 (4.46)
Change at Month 28	-6.4 (4.28)
Change at Month 32	-2.0 (NA)

15. Secondary Outcome

Title	Extension Phase: Change From Extension Phase Baseline in the Functional Assessment Questionnaire (FAQ) Score
Description	The FAQ has 10 items concerned with performing daily tasks necessary for independent living. The caregiver or informant provides performance ratings on 10 complex activities of daily living performed within the preceding 4 weeks. Score ranges from 0 (independent) to 30 (dependent). Lower score indicates that participant can live independently. Higher score indicates that participant cannot live independently.
Time Frame	Baseline, at Month 3, at Month 6, at Month 9, at Month 12, at Month 15, at Month 18, at Month 21, at Month 24, at Month 28 and at Month 32

Outcome Measure Data

Analysis Population Description
The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	41
Baseline	14.4 (7.31)
Change at Month 3	1.3 (5.51)
Change at Month 6	1.4 (3.74)
Change at Month 9	2.2 (4.33)
Change at Month 12	2.6 (4.86)
Change at Month 15	3.0 (5.17)
Change at Month 18	3.4 (4.83)
Change at Month 21	3.0 (3.88)
Change at Month 24	6.8 (5.92)
Change at Month 28	9.2 (4.67)
Change at Month 32	15.0 (NA)

16. Secondary Outcome

Title	Extension Phase: Percent Change From Extension Phase Baseline in Plasma Amyloid (A) Beta(1-x) Measurements at Months 12 and 24
Description	The measurement of the amyloid protein Abeta(1-x), in plasma has been shown to be an important biomarker for alzheimer's disease.
Time Frame	Month 12 and Month 24

Outcome Measure Data

Analysis Population Description
The PD analysis set was the group of participants who had at least 1 post-treatment PD measurement in the extension phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure. Here "number analyzed" signifies participants who were evaluable for this outcome measure at given time points.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	27
Percent Change from Extension Phase Baseline in plasma Abeta(1-x) at Month 12	-71.8 (23.30)
Percent Change from Extension Phase Baseline in plasma Abeta(1-x) at Month 24	-71.1 (31.20)

17. Secondary Outcome

Title	Extension Phase: Percent Change From Extension Phase Baseline in Total Hippocampal Volume at Month 24
Description	Total hippocampal volume is measured by volumetric magnetic resonance imaging (vMRI). Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total hippocampal volume is calculated by summing up right and left hippocampal volumes.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description
The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	12
Mean (Standard Deviation) [percent change]	-4.33 (2.080)

18. Secondary Outcome

Title	Extension Phase: Percent Change From Extension Phase Baseline in Left and Right Hippocampal Volume at Month 24
Description	Left and right hippocampal volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Left and right hippocampal volumes represent a summary measure in the left and right hippocampal regions.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description
The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	12
Percent Change at Month 24 (Left Hippocampal Volume)	-4.31 (2.065)
Percent Change at Month 24 (Right Hippocampal Volume)	-4.37 (2.667)

19. Secondary Outcome

Title	Extension Phase: Percent Change From Extension Phase Baseline in Whole Brain Volume at Month 24
Description	Whole brain volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Whole brain volume represents a summary measure of total brain parenchyma which includes the cerebrum, basal ganglia, diencephalon, and cerebellum.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description
The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	12
Mean (Standard Deviation) [percent change]	-3.26 (1.555)

20. Secondary Outcome

Title	Extension Phase: Percent Change From Extension Phase Baseline in Total Ventricular Volume at Month 24
Description	Total Ventricular Volume is measured by vMRI. Volumetric imaging is a 3D technique where all the MRI signals are collected from the entire tissue sample and imaged as a whole entity, therefore providing a high signal to noise ratio. Total ventricular volume represents a summary measure of total including right and left lateral ventricles, third ventricle and fourth ventricle of brain.
Time Frame	Month 24

Outcome Measure Data

Analysis Population Description
The full analysis set was the group of participants who received at least 1 dose of study drug and had at least 1 post-dose efficacy assessment in the extension phase. Here "overall number of participants analyzed" signifies participants who were evaluable for this outcome measure.

Arm/Group Title	Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
Measure Participants	12
Mean (Standard Deviation) [percent change]	15.18 (8.544)

Adverse Events

	Core Phase: Placebo		Core Phase: Elenbecestat 5 mg Then 50 mg		Core Phase: Elenbecestat 15 mg Then 50 mg		Core Phase: Elenbecestat 50 mg		Extension Phase: Elenbecestat 50 mg
Time Frame	Up to 55 months (Core Phase: Up to 21 months; Extension Phase: Up to 34 months)
Adverse Event Reporting Description	Adverse events were collected for all the participants who were in the safety analysis set. The safety analysis set was the group of participants who received at least 1 dose of study drug (Core and Extension Phase) and had at least 1 post-dose safety assessment (only Core Phase).

Arm/Group Title	Core Phase: Placebo		Core Phase: Elenbecestat 5 mg Then 50 mg		Core Phase: Elenbecestat 15 mg Then 50 mg		Core Phase: Elenbecestat 50 mg		Extension Phase: Elenbecestat 50 mg
Arm/Group Description	Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received two elenbecestat matched-placebo tablets, orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat matched-placebo in core phase.		Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received one elenbecestat 5 mg tablet and one elenbecestat-matched placebo tablet (to maintain blinding), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.		Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 15 mg (one 10 mg and one 5 mg tablets), orally, once daily with food up to 18 months. Participants who remained on treatment were reassigned to elenbecestat 50 mg (two 25 mg tablets) if they had at least 3 months (12 weeks) of treatment remaining in the randomization phase (treatment and follow-up), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.		Participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD received elenbecestat 50 mg (two 25 mg tablets), orally, once daily with food up to 18 months. Participants who completed 18 months treatment or who discontinued taking study drug prematurely were followed up to 3 months (12 weeks) after last dose of elenbecestat in core phase.		Eligible participants with mild cognitive impairment due to AD/prodromal AD and mild to moderate AD who completed the core phase entered the extension phase and received one elenbecestat 50 mg tablet, orally, once daily with or without food until early discontinuation of study drug or early termination of the study, whichever occurred first. Participants were followed up to 3 months (12 weeks) after last dose of elenbecestat in extension phase.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)		0/19 (0%)		0/17 (0%)		1/41 (2.4%)
Serious Adverse Events
	Core Phase: Placebo		Core Phase: Elenbecestat 5 mg Then 50 mg		Core Phase: Elenbecestat 15 mg Then 50 mg		Core Phase: Elenbecestat 50 mg		Extension Phase: Elenbecestat 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/17 (11.8%)		2/17 (11.8%)		5/19 (26.3%)		1/17 (5.9%)		6/41 (14.6%)
Cardiac disorders
Angina pectoris	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Gastrointestinal disorders
Diverticulum Intestinal Haemorrhagic	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
General disorders
Chest pain	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Asthenia	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Infections and infestations
Appendicitis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Influenza	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Cellulitis	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Localised infection	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Affective disorder	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Meningoencephalitis viral	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Pneumonia	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Pneumonia viral	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Wound Infection	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Injury, poisoning and procedural complications
Rib fracture	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Fall	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Musculoskeletal and connective tissue disorders
Spinal column stenosis	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Nervous system disorders
Syncope	0/17 (0%)	0	1/17 (5.9%)	2	1/19 (5.3%)	1	0/17 (0%)	0	1/41 (2.4%)	1
Dementia Alzheimer's type	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Encephalopathy	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Psychiatric disorders
Major depression	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	1	0/41 (0%)	0
Agitation	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Neuropsychiatric symptoms	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Delusion	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Delirium	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Other (Not Including Serious) Adverse Events
	Core Phase: Placebo		Core Phase: Elenbecestat 5 mg Then 50 mg		Core Phase: Elenbecestat 15 mg Then 50 mg		Core Phase: Elenbecestat 50 mg		Extension Phase: Elenbecestat 50 mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	15/17 (88.2%)		15/17 (88.2%)		18/19 (94.7%)		15/17 (88.2%)		30/41 (73.2%)
Blood and lymphatic system disorders
Leukopenia	1/17 (5.9%)	2	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Neutropenia	1/17 (5.9%)	2	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Cardiac disorders
Atrioventricular Block Second Degree	0/17 (0%)	0	1/17 (5.9%)	2	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Cardiac Failure Congestive	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Cardiomegaly	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Heart Valve Incompetence	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Heart Valve Stenosis	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Right Ventricular Enlargement	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Sinus Bradycardia	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Ventricular Extrasystoles	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Ear and labyrinth disorders
Cerumen Impaction	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Vertigo	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	1/17 (5.9%)	1	1/41 (2.4%)	1
Tinnitus	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Endocrine disorders
Thyroid Cyst	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Eye disorders
Dry Eye	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Ocular Rosacea	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Vision Blurred	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Visual Impairment	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Cataract	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Gastrointestinal disorders
Abdominal Pain	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Abdominal Pain Upper	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Anal Incontinence	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Colitis Microscopic	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Constipation	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Diarrhoea	0/17 (0%)	0	2/17 (11.8%)	2	1/19 (5.3%)	1	3/17 (17.6%)	3	0/41 (0%)	0
Dry Mouth	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Dysphagia	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	1/41 (2.4%)	1
Intra-Abdominal Haematoma	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Lip Swelling	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Nausea	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	2/17 (11.8%)	3	1/41 (2.4%)	1
Peritoneal Disorder	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Toothache	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Vomiting	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	1/41 (2.4%)	1
Colitis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Gastrooesophageal Reflux Disease	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Large Intestine Polyp	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Ulcerative Gastritis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
General disorders
Asthenia	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	1	0/41 (0%)	0
Breast Complication Associated With Device	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Fatigue	0/17 (0%)	0	0/17 (0%)	0	3/19 (15.8%)	3	0/17 (0%)	0	0/41 (0%)	0
Gait Disturbance	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Oedema Peripheral	0/17 (0%)	0	0/17 (0%)	0	2/19 (10.5%)	2	0/17 (0%)	0	2/41 (4.9%)	2
Peripheral Swelling	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Propulsive Gait	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Hepatobiliary disorders
Cholelithiasis	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Hepatic Steatosis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Immune system disorders
Seasonal Allergy	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Infections and infestations
Bronchitis	1/17 (5.9%)	1	1/17 (5.9%)	1	0/19 (0%)	0	1/17 (5.9%)	1	2/41 (4.9%)	2
Diverticulitis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Fungal Skin Infection	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Furuncle	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Gastroenteritis Viral	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Gastrointestinal Viral Infection	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Influenza	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Nasopharyngitis	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Oral Herpes	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Rhinitis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Scrotal Infection	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Sinusitis	1/17 (5.9%)	1	2/17 (11.8%)	2	0/19 (0%)	0	0/17 (0%)	0	2/41 (4.9%)	2
Tooth Abscess	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Upper Respiratory Tract Infection	4/17 (23.5%)	6	4/17 (23.5%)	4	1/19 (5.3%)	1	4/17 (23.5%)	6	2/41 (4.9%)	2
Urinary Tract Infection	2/17 (11.8%)	2	2/17 (11.8%)	4	1/19 (5.3%)	3	1/17 (5.9%)	1	3/41 (7.3%)	5
Viral Upper Respiratory Tract Infection	1/17 (5.9%)	2	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Vulvovaginal Candidiasis	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Vulvovaginal Mycotic Infection	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Wound Infection	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Cellulitis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Gastritis Bacterial	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Gastroenteritis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Onychomycosis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Osteomyelitis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Otitis Media	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Respiratory Syncytial Virus Infection	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Tooth Infection	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Injury, poisoning and procedural complications
Accidental Overdose	1/17 (5.9%)	2	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Arthropod Bite	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	1/17 (5.9%)	1	2/41 (4.9%)	2
Arthropod Sting	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Contusion	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	0/17 (0%)	0	2/41 (4.9%)	2
Facial Bones Fracture	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Fall	1/17 (5.9%)	2	1/17 (5.9%)	1	2/19 (10.5%)	2	3/17 (17.6%)	3	4/41 (9.8%)	5
Foot Fracture	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Head Injury	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Laceration	0/17 (0%)	0	1/17 (5.9%)	1	2/19 (10.5%)	2	0/17 (0%)	0	0/41 (0%)	0
Ligament Sprain	1/17 (5.9%)	1	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	2/41 (4.9%)	2
Muscle Strain	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Skin Abrasion	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Wrist Fracture	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Hand Fracture	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	2/41 (4.9%)	2
Meniscus Injury	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	2/41 (4.9%)	2
Product Administration Error	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Skin Laceration	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Spinal Compression Fracture	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Wound	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Investigations
B-Lymphocyte Count Decreased	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	2/17 (11.8%)	2	0/41 (0%)	0
Bacterial Test Positive	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Blood Calcium Decreased	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Blood Cholesterol Increased	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Blood Creatinine Increased	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Blood Glucose Increased	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Blood Immunoglobulin G Increased	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Blood Potassium Decreased	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Blood Potassium Increased	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Blood Pressure Decreased	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Blood Pressure Increased	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Blood Sodium Increased	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Cd4 Lymphocytes Decreased	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Cd8 Lymphocytes Decreased	2/17 (11.8%)	4	0/17 (0%)	0	1/19 (5.3%)	1	2/17 (11.8%)	2	0/41 (0%)	0
Glomerular Filtration Rate Decreased	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Lymphocyte Count Decreased	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Monocyte Count Increased	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Neurological Examination Abnormal	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Neutrophil Count Increased	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Olfactory Test Abnormal	2/17 (11.8%)	2	1/17 (5.9%)	1	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Platelet Count Decreased	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Primitive Reflex Test Positive	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Respiratory Rate Increased	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Romberg Test Positive	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Temperature Perception Test Decreased	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Transaminases Increased	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Urinary Casts	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Weight Decreased	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	1	0/41 (0%)	0
Weight Increased	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
White Blood Cells Urine Positive	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Activated Partial Thromboplastin Time Prolonged	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Liver Function Test Increased	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Occult Blood Positive	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Prostatic Specific Antigen Increased	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Metabolism and nutrition disorders
Decreased Appetite	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	1	0/41 (0%)	0
Dehydration	0/17 (0%)	0	0/17 (0%)	0	2/19 (10.5%)	2	0/17 (0%)	0	0/41 (0%)	0
Gout	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Hypercholesterolaemia	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Hyperglycaemia	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Vitamin D Deficiency	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Hyperlipidaemia	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	1/17 (5.9%)	2	2/17 (11.8%)	2	1/19 (5.3%)	1	0/17 (0%)	0	1/41 (2.4%)	1
Arthritis	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Back Pain	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	1/41 (2.4%)	1
Coccydynia	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Muscle Spasms	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Myalgia	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Osteopenia	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Pain In Extremity	0/17 (0%)	0	0/17 (0%)	0	2/19 (10.5%)	2	0/17 (0%)	0	1/41 (2.4%)	1
Spinal Column Stenosis	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Tendonitis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Flank Pain	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Intervertebral Disc Protrusion	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Pain In Jaw	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	2/41 (4.9%)	2
Skin Papilloma	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Squamous Cell Carcinoma Of Skin	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Adrenal Adenoma	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Nervous system disorders
Cerebellar Microhaemorrhage	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Cerebral Microhaemorrhage	1/17 (5.9%)	1	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	4	0/41 (0%)	0
Decreased Vibratory Sense	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	2/17 (11.8%)	2	0/41 (0%)	0
Dementia	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Disturbance In Attention	1/17 (5.9%)	2	1/17 (5.9%)	1	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Dizziness	1/17 (5.9%)	1	1/17 (5.9%)	1	3/19 (15.8%)	3	0/17 (0%)	0	2/41 (4.9%)	2
Dysgeusia	1/17 (5.9%)	1	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Dysmetria	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Headache	1/17 (5.9%)	1	1/17 (5.9%)	1	3/19 (15.8%)	3	3/17 (17.6%)	3	0/41 (0%)	0
Hypoaesthesia	1/17 (5.9%)	1	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Hypokinesia	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Hyposmia	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	1	0/41 (0%)	0
Memory Impairment	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Neuropathy Peripheral	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Nystagmus	1/17 (5.9%)	1	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Presyncope	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Superficial Siderosis Of Central Nervous System	1/17 (5.9%)	1	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Syncope	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Transient Ischaemic Attack	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Tremor	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	2	1/41 (2.4%)	1
Vasogenic Cerebral Oedema	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Aphasia	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Balance Disorder	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	2/41 (4.9%)	2
Cervical Radiculopathy	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Coordination Abnormal	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Lethargy	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Postural Tremor	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Sciatica	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Dementia Alzheimer's Type	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Psychiatric disorders
Abnormal Dreams	0/17 (0%)	0	2/17 (11.8%)	2	1/19 (5.3%)	1	3/17 (17.6%)	3	0/41 (0%)	0
Agitation	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	3/17 (17.6%)	4	5/41 (12.2%)	6
Anxiety	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Confusional State	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	1/17 (5.9%)	1	1/41 (2.4%)	1
Depressed Mood	0/17 (0%)	0	0/17 (0%)	0	2/19 (10.5%)	2	0/17 (0%)	0	1/41 (2.4%)	1
Depression	1/17 (5.9%)	1	0/17 (0%)	0	2/19 (10.5%)	2	0/17 (0%)	0	3/41 (7.3%)	3
Hallucination, Visual	1/17 (5.9%)	2	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Hypersexuality	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Insomnia	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	1	4/41 (9.8%)	5
Nightmare	1/17 (5.9%)	1	2/17 (11.8%)	2	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Psychotic Disorder	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Rapid Eye Movement Sleep Behaviour Disorder	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Restlessness	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Suicidal Ideation	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	1/17 (5.9%)	1	0/41 (0%)	0
Thinking Abnormal	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Delusion	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Major Depression	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Renal and urinary disorders
Dysuria	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Pollakiuria	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Polyuria	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Renal Artery Stenosis	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Renal Impairment	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Urinary Incontinence	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Reproductive system and breast disorders
Breast Cyst	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Erectile Dysfunction	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Uterine Prolapse	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Atelectasis	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Cough	0/17 (0%)	0	2/17 (11.8%)	2	0/19 (0%)	0	0/17 (0%)	0	3/41 (7.3%)	3
Epistaxis	0/17 (0%)	0	1/17 (5.9%)	2	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Lower Respiratory Tract Congestion	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Nasal Congestion	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Nasal Turbinate Hypertrophy	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Oropharyngeal Pain	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Pleural Thickening	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Rhinorrhoea	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Rhonchi	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Upper Respiratory Tract Congestion	0/17 (0%)	0	1/17 (5.9%)	1	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Hypoxia	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Lung Cyst	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Sleep Apnoea Syndrome	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	2/41 (4.9%)	2
Throat Irritation	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Skin and subcutaneous tissue disorders
Acne	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	2	0/17 (0%)	0	0/41 (0%)	0
Actinic Keratosis	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Alopecia	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Dermatitis	0/17 (0%)	0	1/17 (5.9%)	1	1/19 (5.3%)	1	2/17 (11.8%)	2	0/41 (0%)	0
Dermatitis Contact	1/17 (5.9%)	1	3/17 (17.6%)	3	2/19 (10.5%)	3	3/17 (17.6%)	3	3/41 (7.3%)	3
Erythematotelangiectatic Rosacea	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Hyperhidrosis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Ingrowing Nail	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Night Sweats	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Pruritus	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Skin Lesion	1/17 (5.9%)	1	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Skin Ulcer	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Dermatitis Atopic	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Rash	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Surgical and medical procedures
Rhinoplasty	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Tooth Extraction	1/17 (5.9%)	1	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	0/41 (0%)	0
Cataract Operation	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Hip Arthroplasty	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1
Vascular disorders
Aortic Arteriosclerosis	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	0/17 (0%)	0	0/41 (0%)	0
Hypertension	2/17 (11.8%)	2	0/17 (0%)	0	0/19 (0%)	0	1/17 (5.9%)	1	0/41 (0%)	0
Orthostatic Hypotension	0/17 (0%)	0	0/17 (0%)	0	1/19 (5.3%)	1	1/17 (5.9%)	1	0/41 (0%)	0
Thrombosis	0/17 (0%)	0	0/17 (0%)	0	0/19 (0%)	0	0/17 (0%)	0	1/41 (2.4%)	1

Limitations/Caveats

This study was terminated early by the sponsor on the recommendation of an independent data safety monitoring board following review of unblinded data from the Phase 3 studies E2609-G000-301 (NCT02956486) and E2609-G000-302 (NCT03036280).

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Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title	Eisai Ltd.
Organization	Eisai Medical Information
Phone	+1-888-274-2378
Email	esi_medinfo@eisai.com

Responsible Party:

Eisai Inc.

ClinicalTrials.gov Identifier:

NCT02322021

Other Study ID Numbers:

E2609-G000-202
2014-002723-94

First Posted:

Dec 22, 2014

Last Update Posted:

Mar 5, 2021

Last Verified:

Mar 1, 2021

Dose-Finding Study To Evaluate Safety, Tolerability, and Efficacy of E2609 in Participants With Mild Cognitive Impairment Due to Alzheimer's Disease (Prodromal Alzheimer's Disease) and Mild to Moderate Dementia Due to Alzheimer's Disease

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion criteria:

Participants must meet all of the following criteria to be included in this study:

Exclusion criteria:

Participants who meet any of the following criteria will be excluded from this study:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

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Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

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