An Efficacy and Safety Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease

Alzheimer´s Disease Clinical Trial

— AMARANTH  

Official title:

A 24-month, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy, Safety, Tolerability, Biomarker, and Pharmacokinetic Study of AZD3293 in Early Alzheimer's Disease (The AMARANTH Study)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02245737
• Other study ID #: 16023
• Secondary ID: I8D-MC-AZES2014-
• Status: Terminated
• Phase: Phase 2/Phase 3
• Start date: September 30, 2014
• Est. completion date: October 4, 2018

Study information

• Verified date: October 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of lanabecestat compared with placebo administered for 104 weeks in the treatment of early Alzheimer´s disease. The study will test the hypothesis that lanabecestat is a disease-modifying treatment for participants with early Alzheimer´s disease, defined as the continuum of participants with mild cognitive impairment (MCI) due to Alzheimer´s disease and participants diagnosed with mild dementia of the Alzheimer´s type, as measured by change from baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) score at week 104 in each of the 2 lanabecestat treatment groups compared with placebo.

Description:

Participants who meet other study entry requirements will be required to undergo either an amyloid positron emission tomography (PET) scan or a lumbar puncture for cerebrospinal fluid (CSF) sampling at screening to document presence of abnormal levels of brain and CSF amyloid for study inclusion. The study includes 2 sub-studies: the participants that undergo a PET scan at screening will be included in the PET-substudy, and participants who undergo a lumbar puncture at screening will be included in the CSF substudy until each of these substudies are completed.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2218
• Est. completion date: October 4, 2018
• Est. primary completion date: October 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

• Gradual and progressive change in the participant's memory function over more than 6 months, reported by participant and study partner

• Mini-Mental State Examination score of 20-30 inclusive at screening

• Objective impairment in memory as evaluated by memory test performed at screening

• For a diagnosis of mild Alzheimer's Disease (AD), participant meets the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria for probable AD

• For a diagnosis of MCI due to AD, participant meets NIA-AA criteria for MCI due to AD

Exclusion Criteria:

• Significant neurological disease affecting the central nervous system, other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson´s disease, or epilepsy or recurrent seizures

• History of clinically evident stroke, or multiple strokes based on history or imaging results

• History of clinically important carotid or vertebrobasilar stenosis or plaque

• History of multiple concussions with sustained cognitive complaints or objective change in neuropsychological function in the last 5 years

• Participants with a current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of Major Depressive Disorder or any current primary psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the participant´s ability to complete the study

• History of alcohol or drug abuse or dependence (except nicotine dependence) within 2 years before the screening

• Within 1 year before the screening or between screening and baseline, any of the following: myocardial infarction; moderate or severe congestive heart failure, New York Heart Association class III or IV; hospitalization for, or symptom of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (eg, significant valvular disease, hypertrophic cardiomyopathy), or hospitalization for arrhythmia

• Congenital QT prolongation

• History of cancer within the last 5 years, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-progressive prostate cancer or other cancers with low-risk of recurrence or spread

• Current serious or unstable clinically important systemic illness that, in the judgment of the investigator, is likely to affect cognitive assessment, deteriorate, or affect the participant's safety or ability to complete the study, including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, or hematologic disorders

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer´s Disease

Intervention

Drug:
• Lanabecestat
Administered orally
• Placebo
Administered orally

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Box Hill Hospital	Box Hill	Victoria
Australia	Delmont Private Hospital	Glen Iris	Victoria
Australia	Griffith University	Gold Coast	Queensland
Australia	Heidelberg Repatriation Hospital	Heidelberg	Victoria
Australia	Southern Neurology	Kogarah	New South Wales
Australia	Australian Alzheimer's Research Foundation	Nedlands	Western Australia
Australia	Neuro Trials Victoria Pty Ltd	Noble Park
Australia	The Florey Institute of Neuroscience and Mental Health	Parkville	Victoria
Belgium	Hospital Universitaire Erasme Brussel	Brussel
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Hopital Universitaire Brugmann Brussel	Brussels
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Jessa Ziekenhuis	Hasselt	Limburg
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Belgium	Heilig Hartziekenhuis	Roeselare
Canada	Clinique de la Memoire de l'Outaouais	Gatineau	Quebec
Canada	NeuroSearch Developements	Greenfield Park	Quebec
Canada	True North Clinical Research Halifax, LLC	Halifax	Nova Scotia
Canada	The Medical Arts Health Research Group	Kamloops	British Columbia
Canada	Okanagan Clinical Trials	Kelowna	British Columbia
Canada	Hopital Maisonneure-Rosemount	Montreal	Quebec
Canada	Bruyere Continuing Care	Ottawa	Ontario
Canada	Kawartha Regional Memory Clinic	Peterborough	Ontario
Canada	Hopital de L'Enfant Jesus	Quebec City	Quebec
Canada	CSSS-Institut Universitaire Gériatric de Sherbrooke	Sherbrooke	Qubec
Canada	Q&T Research Sherbrooke Inc	Sherbrooke	Quebec
Canada	Toronto Memory Program	Toronto	Ontario
Canada	Toronto Western Hospital	Toronto	Ontario
Canada	University of British Columbia	Vancouver	British Columbia
Canada	Royal Jubilee Hospital	Victoria	British Columbia
France	Hopital Neuro Pierre Wertheimer	Bron Cedex
France	CHU Dijonon	Dijon Cedex
France	CHRU Lille - Hopital Roger Salengro	Lille Cedex
France	CHU Hopital de la Timone	Marseille Cedex 05
France	Chu de Nantes Hopital Laennec	Nantes
France	Hopital Broca	Paris
France	Hopital de la Pitie Salpetriere	Paris
France	Hopital Lariboisière	Paris
France	CHU de Toulouse	Toulouse
France	CHU de Toulouse Hopital Purpan	Toulouse	Cedex 9
France	Hopital des Charpennes	Villeurbanne
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Gemeinschaftspraxis Dr. R. Ehret & Dr. W. von Pannwitz	Berlin
Germany	Praxis Dr. Lauter	Bochum	Nordrhein-Westfalen
Germany	St Josef-Hospital Bochum	Bochum	Nordrhein-Westfalen
Germany	Universitätsklinikum Bonn	Bonn	Nordrhein-Westfalen
Germany	Arztpraxis Dr. Christian Oehlwein	Gera	Thüringen
Germany	Martin-Luther-Universität Halle-Wittenberg	Halle (Saale)	Sachsen-Anhalt
Germany	Universitätsklinikum des Saarlandes	Homburg	Saarland
Germany	Gemeinschaftspraxis für Neurologie Prof. Gereon Nelles	Köln	Nordrhein-Westfalen
Germany	Universitätsklinikum Köln	Köln	Nordrhein-Westfalen
Germany	Universitätsklinikum Otto-von-Guericke-Universität	Magdeburg	Sachsen-Anhalt
Germany	Pharmakologisches Studienzentrum Chemnitz	Mittweida	Sachsen
Germany	Klinikum Rechts der Isar der TU München	München	Bayern
Germany	Studien und Gedächtniszentrum München	München	Bayern
Germany	Institut fur Psychogerontologie	Nürnberg	Bayern
Germany	Neurozentrum Prien	Prien am Chiemsee	Bayern
Germany	Neurologische Praxis Siegen	Siegen	Nordrhein-Westfalen
Germany	Universitätsklinikum Tübingen	Tübingen	Baden-Württemberg
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Germany	Institut für Neuropsychiatrie INP3	Wenzenbach	Bayern
Germany	Studienzentrum Nord-West	Westerstede	Niedersachsen
Hungary	Del-pesti Centrumkorház - Orszagos Hematologiai és Infektologiai Intezet	Budapest
Hungary	Semmelweis Medical University	Budapest
Hungary	Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz	Debrecen
Hungary	Debreceni Egyetem Klinikai Kozpont	Debrecen
Hungary	PTE KK Pszichiatriai es Pszichoterapias Klinika	Pecs	Baranya
Hungary	Univerisity of Szeged	Szeged
Italy	Università Politecnica delle Marche Torrette	Ancona
Italy	IRCCS San Giovanni di Dio Fatebenefratelli	Brescia
Italy	Fondazione San Raffaele Giglio di Cefalu	Cefalu	Palermo
Italy	Fondazione Universitaria degli Studi G D'Annunzio	Chieti
Italy	Ente Ospedaliero Ospedali Galliera	Genova
Italy	Fondazione IRCCS Ca'Granda Ospedale Maggiore Policinico	Milano
Italy	Nuovo Ospedale Civile Sant'Agostino Estense	Modena
Italy	Azienda Ospedaliera San Gerardo	Monza	Milano
Italy	Universita Di Pisa	Pisa	PI
Italy	Ospedale Degli Infermi ASR USSL 12	Ponderano	Biella
Italy	Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza	Roma
Italy	Ospedale San Giovanni Calibita Fatebenefratelli	Roma
Italy	Policlinico Ospedale S. Andrea	Roma
Italy	Policlinico Univ. Agostino Gemelli	Roma
Italy	Azienda Ospedaliera Citta della Salute della Scienza Torino	Torino
Japan	National Hospital Organization Asahikawa Medical Center	Asahikawa	Hokkaido
Japan	Nippon Medical School Hospital	Bunkyo-Ku	Tokyo
Japan	The University of Tokyo Hospital	Bunkyo-ku	Tokyo
Japan	National Chiba-East-Hospital	Chuo-ku	Chiba
Japan	Fukuoka University Hospital	Fukuoka
Japan	Koshokai aino hospital	Ibaraki	Osaka
Japan	Ina Central Hospital	Ina	Nagano
Japan	Saitama Medical University Hospital	Iruma-Gun	Saitama
Japan	Shonan Kamakura General Hospital	Kamakura	Kanagawa
Japan	Nihon Kokan Hospital	Kawasaki	Kanagawa
Japan	Katayama Medical Clinic	Kurashiki	Okayama
Japan	Kyoto Minami Hospital	Kyoto
Japan	Kyoto University Hospital	Kyoto
Japan	Utano Hospital	Kyoto
Japan	Kyoto Prefectural University of Medicine	Kyoto-shi	Kyoto
Japan	Rakuwakai Otowarehabilitation Hospital	Kyoto-shi	Kyoto
Japan	Matsumoto Medical Center	Matsumoto	Nagano
Japan	Nozomi Memory Clinic	Mitaka-shi	Tokyo
Japan	Iwate Medical University Hospital	Morioka	Iwate
Japan	National Sanatorium Hokuriku Hospital	Nanto	Toyama
Japan	National Institute for Longevity Sciences NCGG	Obu	Aichi
Japan	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Osaka
Japan	Sakaguchi Clinic	Sakai	Osaka
Japan	Sangenjaya Nakamura Mental Clinic	Setagaya	Tokyo
Japan	Kanauchi Medical Clinic	Shinjuku-ku	Tokyo
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo
Japan	National Sanatorium Toneyama Hospital	Toyonaka	Osaka
Japan	Memory Clinic Ochanomizu	Tsukuba	Tokyo
Japan	Tsukuba University Hospital	Tsukuba	Ibaraki
Japan	Shiroma Clinic	Urasoe	Okinawa
Japan	Yokohama City University Hospital	Yokohama	Kanagawa
Korea, Republic of	The Catholic University of Korea-Bucheon St. Mary's Hospital	Bucheon-si	Gyeonggi-do
Korea, Republic of	Hanyang University Guri Hospital	Guri-si	Gyeonggido
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Gachon University Gil Medical Center	Namdong	Incheon
Korea, Republic of	Dong-A University Medical Center	Seogu	Busan
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Geonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok	Podlaskie
Poland	NZOZ Dom Sue Ryder - Pallmed Sp. z o.o.	Bydgoszcz
Poland	NZOZ Wielospecjalistyczna Poradnia Lekarska	Katowice
Poland	Specjalistyczna Praktyka Lekarska prof. Grzegorz Opala	Katowice
Poland	Centrum Zdrowia Psychicznego	Kielce
Poland	Centrum Neurologii Klinicznej	Krakow
Poland	Medycyna Milorzab	Lodz	Lódzkie
Poland	Instytut Medycyny Wsi	Lublin
Poland	NZOZ Neuromed M. I M. Nastaj sp. P.	Lublin
Poland	NEURO-CARE Sp. z o.o. Sp. Komandytowa	Siemianowice Slaskie
Poland	Centralny Szpital Kliniczny MSW	Warszawa
Poland	Centrum Medyczne	Warszawa
Poland	NZOZ Wroclawskie Centrum Alzheimerowskie	Wroclaw	Dolnoslaskie
Puerto Rico	Santa Cruz Behavioral PSC	Bayamon
Puerto Rico	Ivonne Z. Jimenez-Velazquez, MD	Carolina
Puerto Rico	Instituto de Neurologia Dra. Ivonne Fraga	San Juan
Puerto Rico	Michel A. Woodbury-Farina, MD.	San Juan
Romania	Policlinica CCBR S.R.L.	Bucuresti
Romania	SC Centrul Medical Sana SRL	Bucuresti
Romania	SC Med Life SA	Bucuresti
Romania	SC Med Life SA	Timisoara
Spain	Fundacion ACE-Institut Catala de Neurociences Aplicades	Barcelona
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Santa Creu I Sant Pau	Barcelona
Spain	Hospital Universitari de Bellvitge	Barcelona
Spain	Hospital Reina Sofia	Cordoba
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Centro de Atencion Especializada (CAE) OROITU	Getxo	Vizcaya
Spain	Hospital De La Princesa	Madrid
Spain	Hospital Universitario De Getafe	Madrid	Getafe
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Puerta De Hierro	Majadahonda	Madrid
Spain	Hospital Son Espases	Palma de Mallorca
Spain	Hospital Virgen Del Puerto	Plasencia	Caceres
Spain	Hospital Univ Sant Joan de Reus, S.A.	Reus
Spain	Fundacion CITA Alzheimer	San Sebastian
Spain	Hospital General de Catalunya	Sant Cugat del Valles	Barcelona
Spain	Hospital Doctor Peset	Valencia
Spain	Hospital Universitario La Fe de Valencia	Valencia
United Kingdom	MAC UK Neuroscience Ltd	Blackpool	Lancs
United Kingdom	West London Mental Health NHS Trust	Brentford
United Kingdom	MAC Clinical Research	Cannock	Staffordshire
United Kingdom	Cognitive Treatment & Research Unit	Crowborough	East Sussex
United Kingdom	Glasgow Memory Clinic	Glasgow
United Kingdom	Guildford Nuffield Hospital	London
United Kingdom	Hammersmith Hospital	London
United Kingdom	Re-Cognition Health Ltd	London
United Kingdom	MAC Clinical Research	Manchester
United Kingdom	Plymouth Hospitals NHS Trust	Plymouth	Devon
United Kingdom	Southern Health NHS	Southampton	Hampshire
United Kingdom	MAC Clinical Research	Stourton	Leeds
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Community Clinical Research Center	Anderson	Indiana
United States	Atlanta Center of Medical Research	Atlanta	Georgia
United States	The Multiple Sclerosis Center of Atlanta	Atlanta	Georgia
United States	Senior Adults Specialty Research Inc	Austin	Texas
United States	The Memory Clinic	Bennington	Vermont
United States	Integrative Clinical Trials, LLC	Brooklyn	New York
United States	SPRI Clinical Trials, LLC.	Brooklyn	New York
United States	Alzheimer's Disease and Memory Disorders Center	Buffalo	New York
United States	Valley Medical Primary Care	Centerville	Ohio
United States	Roper St. Francis Healthcare	Charleston	South Carolina
United States	Alzheimer's Memory Center	Charlotte	North Carolina
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Christ Hospital	Cincinnati	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	The Corvallis Clinic P.C.	Corvallis	Oregon
United States	Texas Health Physicians Group	Dallas	Texas
United States	Brain Matters Research	Delray Beach	Florida
United States	Mile High Research Center	Denver	Colorado
United States	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island
United States	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey
United States	Alexian Brothers Medical Center	Elk Grove Village	Illinois
United States	Medical Group of Texas	Fort Worth	Texas
United States	Positron Research International	Fremont	California
United States	Radiant Research	Greer	South Carolina
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Berma Research	Hialeah	Florida
United States	Direct Helpers Medical Center	Hialeah	Florida
United States	Galiz Research	Hialeah	Florida
United States	MaxBlue Institute	Hialeah	Florida
United States	University of Texas Health Services Center - Houston	Houston	Texas
United States	Indiana University School of Medicine	Indianapolis	Indiana
United States	Quillen College of Medicine, East TN State University	Johnson City	Tennessee
United States	Alliance Research Centers	Laguna Hills	California
United States	Senior Clinical Trials, Inc.	Laguna Hills	California
United States	Alzheimer's Research and Treatment Center	Lake Worth	Florida
United States	Empire Neurology, PC	Latham	New York
United States	AdvanceMed Research	Lawrenceville	New Jersey
United States	Collaborative Neuroscience Network - CNS	Long Beach	California
United States	Alzheimer's Research Company	Manchester	New Jersey
United States	ActivMed Practices & Research, Inc	Methuen	Massachusetts
United States	Advance Medical Research Institute	Miami	Florida
United States	Allied Biomedical Research Institute, Inc.	Miami	Florida
United States	JDH Medical Group, LLC	Miami	Florida
United States	Medical Research Center	Miami	Florida
United States	Miami Jewish Health Systems	Miami	Florida
United States	New Horizon Research Center	Miami	Florida
United States	Institute for Neurodegenerative Disorders	New Haven	Connecticut
United States	Clinilabs, Inc (New York)	New York	New York
United States	Columbia University Medical Center	New York	New York
United States	Boston Center for Memory	Newton	Massachusetts
United States	Compass Research	Orlando	Florida
United States	IMIC, Inc.	Palmetto Bay	Florida
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	St Josephs Hospital and Medical Center	Phoenix	Arizona
United States	University of Rochester	Rochester	New York
United States	Millennium Psychiatric Associates, LLV	Saint Louis	Missouri
United States	St. Louis Clinical Trials, LC	Saint Louis	Missouri
United States	Suncoast Neuroscience Associates	Saint Petersburg	Florida
United States	University of Utah School of Medicine	Salt Lake City	Utah
United States	Pacific Research Network Inc	San Diego	California
United States	San Francisco Clinical Research Center	San Francisco	California
United States	Roskamp Institute	Sarasota	Florida
United States	Carman Research	Smyrna	Georgia
United States	Springfield Neurology Associates	Springfield	Massachusetts
United States	The Cognitive and Research Center of NJ	Springfield	New Jersey
United States	Banner Sun Health Research Institute	Sun City	Arizona
United States	Infinity Clinical Research, LLC	Sunrise	Florida
United States	Olympian Clinical Research	Tampa	Florida
United States	Stedman Clinical Trials	Tampa	Florida
United States	Compass Research	The Villages	Florida
United States	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey
United States	Bio Behavioral Health	Toms River	New Jersey
United States	Territory Neurology & Research Institute	Tucson	Arizona
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Neurology Specialists of Monmouth County	West Long Branch	New Jersey
United States	Premiere Research Institute at Palm Beach Neurology	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Hungary,  Italy,  Japan,  Korea, Republic of,  Poland,  Puerto Rico,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)	ADAS-Cog13 (13-item version of ADAS-Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment-by-visit interaction, disease status at baseline, apolipoprotein E4 (APOE4) status, acetylcholinesterase inhibitor (AChEI) use at baseline, pooled country, and covariates for baseline ADAS-Cog13 total score, age at baseline, and baseline ADAS-Cog13 total score-by-visit interaction.	Baseline, Week 104
Secondary	Change From Baseline on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL)	The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, pooled country, and covariates for baseline for baseline iADL score, age at baseline, and baseline iADL score-by-visit interaction.	Baseline, Week 104
Secondary	Change From Baseline on the Functional Activities Questionnaire (FAQ) Score	FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now = 1; Never did [the activity] but could do now = 0; Normal = 0; Has difficulty but does by self = 1; Requires assistance = 2; Dependent = 3). FAQ scale is 0 to 30, with higher scores indicating greater impairment. LS Mean was calculated by MMRM with factors for treatment, visit, treatment-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline and pooled country.	Baseline, Week 104
Secondary	Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score	The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by- visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, pooled country, and covariates for baseline iADRS13 total score, age at baseline, and baseline iADRS13 total score-by-visit interaction.	Baseline, Week 104
Secondary	Change From Baseline on the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score	The CDR-SB is a rater administered scale and impairment is scored in of the following categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which no dementia = 0, questionable dementia = 0.5, mild dementia = 1, moderate dementia = 2 and severe dementia = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher scores indicating greater impairment. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, pooled country, and covariates for baseline CDR-SB score, age at baseline, and baseline CDR-SB score-by-visit interaction.	Baseline, Week 104
Secondary	Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage	The CDR global score is a composite score calculated using the Washington University CDR-assignment algorithm applied to the 6 individual domain box scores (Morris 1993). The memory domain is considered the primary category that drives the CDR global outcome, and all other domains are secondary. The CDR global score ranges from 0 to 3 (0 = no dementia, 0.5 = questionable dementia, 1 = mild dementia, 2 = moderate dementia, 3 = severe dementia).	Baseline through Loss of 1 Global Stage or Week 104
Secondary	Change From Baseline in Neuropsychiatric Inventory (NPI) Score	The NPI is a questionnaire administered to caregivers that quantifies behavioral changes. Each of the 12 behavioral domains the caregiver reports as present are scored for Frequency, scale: 1 (Occasionally) to 4 (Very Frequently), and Severity, scale: 1 (Mild) to 3 (Severe). If the domain is reported by the caregiver as 'Not Affected,' that domain is scored as 0. The individual domain scores are calculated by multiplying the frequency times the severity for each domain. NPI Total Score is calculated by adding the individual domain scores together for all 12 domains, with a scores range from 0 to 144, with higher scores indicating greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, pooled country, and covariates for baseline NPI score, age at baseline, and baseline NPI score-by-visit interaction.	Baseline, Week 104
Secondary	Change From Baseline on the Mini-Mental State Examination (MMSE)	The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, pooled country, and covariates for baseline MMSE total score, age at baseline, and baseline MMSE total score-by-visit interaction.	Baseline, Week 104
Secondary	Pharmacodynamics (PD): Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aß)1-42	Concentration of the peptide Aß 1-42 in plasma measured by validated immunoassay. LS Mean was determined by Analysis of covariance (ANCOVA) with last observation carried forward (LOCF), terms for treatment, baseline biomarker and age at baseline.	Baseline, Week 97
Secondary	PD: Percent Change From Baseline in Concentration of CSF Biomarker Aß1-40	Concentration of the peptide Aß 1-40 in plasma measured by immunoassay. LS Mean was determined by ANCOVA with LOCF (last observation carried forward), terms for treatment, baseline biomarker and age at baseline.	Baseline, Week 97
Secondary	Change From Baseline in CSF Total Tau	Cerebrospinal fluid samples are collected for analysis of concentration total tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, disease status at baseline, baseline biomarker and age at baseline.	Baseline, Week 97
Secondary	Change From Baseline in CSF Phosphorylated Tau	Cerebrospinal fluid samples are collected for analysis of concentrations of phosphorylated tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, disease status at baseline, baseline biomarker and age at baseline.	Baseline, Week 97
Secondary	Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan	Amyloid deposition in the brain is one of the defining neuropathologic findings of Alzheimer's disease. Florbetapir exhibits high affinity specific binding to amyloid plaques. The change from baseline was measured as average standard uptake value ratio (SUVr) in prespecified regions of interest (ROI) assessed by florbetapir amyloid PET imaging in a subset of participants. The Centiloid scale standardizes quantitative brain amyloid PET results to allow cross-tracer and cross-methodology comparisons. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans. Florbetapir SUVr was converted to the Centiloid scale using the following conversion: Florbetapir Centiloids = 183 x SUVr - 177. LS Mean was determined by ANCOVA methodology with factors for treatment, disease status at baseline, baseline biomarker and age at baseline.	Baseline, Week 104
Secondary	Change From Baseline in Tau PET ((Flortaucipir F18)	Tau PET tracer (flortaucipir F18) longitudinal study measured whether lanabecestat, in participants with mild AD dementia, affected tau density and distribution over time. The outcome reported is the composite summary of the standard uptake value ratio (SUVR) normalized to the signal intensity in white matter. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA methodology with factors for treatment, disease status at baseline, baseline biomarker and age at baseline. Baseline defined to be within 28 days of starting study drug.	Baseline, Week 104
Secondary	Change From Baseline in Brain Metabolism Using Fluorodeoxyglucose (FDG)	Fluorodeoxyglucose (FDG) PET evaluates the regional brain metabolic rates for glucose as a sensitive, in vivo metabolic index of brain function. The outcome reported is the composite summary of the standard uptake value ratio (SUVR) normalized to the pons + vermis assessed with composite meta and composite meta automated anatomical labeling atlas (ALL). Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA methodology with factors for treatment, disease status at baseline, baseline biomarker and age at baseline. Baseline defined to be within 28 days of starting study drug.	Baseline, Week 104
Secondary	Change From Baseline in Whole Brain Volume	Magnetic resonance imaging (MRI) was used to evaluate the effect of lanabecestat on whole brain volumes. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA methodology with factors for treatment, baseline vMRI, intracranial volume, disease status at baseline and age at baseline.	Baseline, Week 104
Secondary	Pharmacokinetics (PK): Plasma Concentration of Lanabecestat		Week 4, post dose prior to departure from the clinic

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