A Study of Lanabecestat (LY3314814) in Participants With Mild Alzheimer's Disease Dementia

Alzheimer's Disease Clinical Trial

— DAYBREAK-ALZ  

Official title:

A Randomized, Double-Blind, Placebo-Controlled and Delayed-Start Study of LY3314814 in Mild Alzheimer's Disease Dementia

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02783573
• Other study ID #: 16024
• Secondary ID: I8D-MC-AZET2015-
• Status: Terminated
• Phase: Phase 3
• Start date: July 1, 2016
• Est. completion date: September 28, 2018

Study information

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

Clinical Trial Summary

The main purpose of this study is to evaluate the efficacy of the study drug known as lanabecestat in participants with mild Alzheimer's disease (AD) dementia.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1722
• Est. completion date: September 28, 2018
• Est. primary completion date: September 28, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years to 85 Years

Eligibility

Inclusion Criteria:

• Participant must meet the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (NIA-AA) criteria for probable AD dementia.

• MMSE score of 20 to 26 inclusive at screening visit.

• For a diagnosis of mild AD dementia, participant must have a CDR global score of 0.5 or 1, with the memory box score =0.5 at screening.

• Evidence of amyloid pathology.

• The participant must have a reliable study partner with whom he/she cohabits or has regular contact.

Exclusion Criteria:

• Significant and/or current 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, repetitive head trauma, serious infection of the brain, Parkinson's disease, epilepsy, or cervicocranial vascular disease.

• Participants with 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 assessment, or affect the participant's ability to complete the study. Participants with history of schizophrenia or other chronic psychosis are excluded.

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

• Congenital QT prolongation.

• Intermittent second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia.

• A corrected QT (QTcF) interval measurement >470 milliseconds (men and women) at screening (as determined at the investigational site).

• History of malignant cancer within the last 5 years.

• History of vitiligo and/or current evidence of post-inflammatory hypopigmentation.

• Calculated creatinine clearance <30 milliliters per minute (Cockcroft-Gault formula; Cockcroft and Gault 1976) at screening.

• Currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Dementia

Intervention

Drug:
• Lanabecestat
Administered orally
• Placebo
Administered orally

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	Recherches Neuro-Hippocampe Inc	Gatineau	Quebec
Canada	True North Clinical Research Halifax, LLC	Halifax	Nova Scotia
Canada	Bruyere Continuing Care	Ottawa	Ontario
Canada	Kawartha Regional Memory Clinic	Peterborough	Ontario
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 Sunnybrook Regional Cancer Center	Toronto	Ontario
Canada	Douglas Hospital and Research Centre	Verdun	Quebec
Canada	The Medical Arts Health Research Group	West Vancouver	British Columbia
China	Beijing 301 Hospital	Beijing	Beijing
China	Xuanwu Hospital-Capital Medical University	Beijing	Beijing
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Guangzhou First People's Hospital	Guangzhou	Guangdong
China	The First Affiliated Hospital, Zhejiang University	Hangzhou	Zhejiang
China	Nanjing Drum Tower Hosp Affiliated Hosp of Nanjing Univ Med	Nanjing	Jiangsu
China	Zhongda Hospital-Southeast University	Nanjing	Jiangsu
China	Qingdao Municipal Hospital	Qingdao	Shandong
China	Shanghai Huashan Hospital Affil to Fu Dan University	Shanghai
China	Shanghai Tongji Hospital(CCBR site)	Shanghai	Shanghai
China	Tangshan Worker Hospital	Tangshan	Hebei
China	The First Affiliated Hospital of Wenzhou Medical College	Wenzhou	Zhejiang
China	Northern Jiangsu People's Hospital	Yangzhou	Jiangsu
Czechia	Fakultni nemocnice u sv. Anny v Brne	Brno
Czechia	Neurohk s.r.o.	Chocen
Czechia	Neuropsychiatrie s.r.o	Hradec Kralove
Czechia	Brain-Soultherapy s.r.o	Kladno
Czechia	A-Shine s.r.o.	Plzen
Czechia	Clintrial, s.r.o.	Praha 10
Czechia	Medical Services Prague s.r.o.	Praha 6
Czechia	Neuropsychiatrie s.r.o	Praha 6
Czechia	Axon Clinical, s.r.o.	Praha 8
Denmark	CCBR-Alborg-DK	Aalborg
Denmark	Center For Clinical and Basic Research	Ballerup
Denmark	Rigshospitalet	Copenhagen
Denmark	Center for Clinical and Basic Research -CCBR	Vejle
France	CHU d'Amiens-Picardie Hopital Sud	Amiens Cedex 1
France	CHU de Caen Hopital Cote de Nacre	Caen Cedex
France	APHM Hôpital de la Timone	Marseille
France	Institut Claude Pompidou - CMRR	Nice	Alpes Maritimes
France	Hôpital de la Pitié-Salpêtrière	Paris
France	CHU Rennes/Hopital Sud	Rennes Cedex	Ille Et Vilaine
France	CHU Saint Etienne - Hopital Nord	Saint Priest en Jarez	Loire
France	CHU Strasbourg Hôpital de Hautepierre	Strasbourg Cedex
France	Chu de Toulouse Hopital de La Grave	Toulouse Cedex
France	Chu De Nancy Hop D'Adultes De Brabois	Vandœuvre-lès-Nancy	Meurthe-et-Moselle
Germany	MVZ LiO Berlin	Berlin
Germany	Praxis Dr. Erich Scholz	Böblingen	Baden-Württemberg
Germany	Diakoniekrankenhaus Henriettenstiftung Hannover	Hannover	Niedersachsen
Germany	ISPG - Institut für Studien zur psychischen Gesundheit	Mannheim	Baden-Württemberg
Germany	Klinikum der Universität München	München	Bayern
Germany	Klinikum Rechts der Isar der TU München	München	Bayern
Germany	Praxis für Neurologie und Psychiatrie Dr. med. Roth	Ostfildern	Baden-Württemberg
Germany	Neurozentrum Sophienstraße	Stuttgart	Baden-Württemberg
Germany	Neuropraxis München Süd	Unterhaching	Bayern
Italy	Spedali Civili - Universita degli Studi	Brescia
Italy	Azienda Ospedaliera Universitaria Careggi	Firenze
Italy	Ente Ospedaliero Ospedali Galliera	Genova
Italy	IRCCS Azienda Ospedaliera Universitaria San Martino	Genova
Italy	SDN - Istituto di Ricerca Diagnostica e Nucleare	Napoli
Italy	Azienda Ospedaliera - Universitaria Pisana	Pisa
Italy	IRCCS Santa Lucia	Roma
Italy	Policlinico Univ. Agostino Gemelli	Roma	Lazio
Italy	Universita La Sapienza	Roma
Italy	Azienda Ospedaliera Citta della Salute della Scienza Torino	Torino
Japan	Takeda General Hospital	Aizu-Wakamatsu	Fukushima
Japan	Shinwakai Yachiyo Hospital	Anjo-shi	Aichi-Ken
Japan	Aomori Prefectural Centeral Hospital	Aomori
Japan	Juntendo University Hospital	Bunkyo-ku	Tokyo
Japan	Memory Clinic Ochanomizu	Bunkyo-ku	Tokyo
Japan	Inage Neurology and Memory Clinic	Chiba-shi	Chiba-Ken
Japan	Keikokai P-One Clinic	Hachioji-shi	Tokyo-To
Japan	Koseikai Kusatsu Hospital	Hiroshima-shi	Hiroshima-Ken
Japan	NHO Hizen Psychiatric Center	Kanzaki-gun	Saga-Ken
Japan	Nara Medical University Hospital	Kashihara	Nara
Japan	Ikeuchi Psycho Induced Internal Clinic	Kobe-shi
Japan	Yuge Hospital	Kumamoto
Japan	Katayama Medical Clinic	Kurashiki-shi	Okayama-Ken
Japan	Koseikai Takeda Hospital	Kyoto-Shi	Kyoto-Fu
Japan	Musashino Red Cross Hospital	Musashino	Tokyo
Japan	Kojunkai Daido Hospital	Nagoya-Shi	Aichi-Ken
Japan	Nagoya Ekisaikai Hospital	Nagoya-shi	Aichi-Ken
Japan	JADECOM Nara City Hospital	Nara-Shi	Nara-Ken
Japan	NHO Niigata Hospital	Niigata
Japan	Himuro Neurology Clinic	Osaka-Shi	Osaka-Fu
Japan	Kotobukikai Tominaga Clinic	Osaka-shi	Osaka-Fu
Japan	NHO Hiroshima-Nishi Medical Center	Otaki-Shi	Hiroshima-Ken
Japan	NHO Hokkaido Medical Center	Sapporo-shi
Japan	Jisenkai Nanko Psychiatric Institute	Shirakawa-shi	Fukushima-Ken
Japan	Shimizu Hospital	Shizuoka-shi	Shizuoka
Japan	Kousaiin Hospital	Suita-shi	Osaka-Fu
Japan	Ehime University Hospital	Toon-Shi	Ehime-Ken
Japan	Uji Takeda Hospital	Uji-Shi	Kyoto-Fu
Japan	Yokohama Hospital	Yokohama	Kanagawa
Japan	JOHAS Sanin Rosai Hospital	Yonago-shi	Tottori-Ken
Japan	Oita University Hospital	Yufu-shi	Oita-Ken
Korea, Republic of	The Catholic University of Korea-Bucheon St. Mary's Hospital	Bucheon-si	Gyeonggi-do
Korea, Republic of	Dong-A University Medical Center	Busan	Busan Gwang'yeogsi
Korea, Republic of	Myongji Hospital	Goyang-si	Gyeonggi-do
Korea, Republic of	Inha University Hospital	Incheon
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si	Gyeonggi-do
Korea, Republic of	Hanyang University Medical Center	Seoul
Korea, Republic of	Konkuk University Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Mexico	Mexico Centre for Clinical Research SA de CV	Mexico City	Distrito Federal
Mexico	Accelerium Clinical Research	Monterrey	Nuevo Leon
Mexico	Avix Investigación Clínica, S.C	Monterrey	Nuevo León
Mexico	Centro de Estudios Clinicos y Esp Medicas SC	Monterrey	Nuevo Leon
Mexico	Hospital Univ. Jose Eleuterio Gonzalez	Monterrey	N.l.
Mexico	Instituto de Informacion en Salud Mental (INFOSAM)	Monterrey	NL
Mexico	Hospital Universitario de Saltillo	Saltillo	Coahuila
Mexico	Clinical Research Institute S C	Tlalnepantla	Edo De Mex
Netherlands	Emotional Brain B.V.	Almere
Netherlands	Brain Research Center	Amsterdam
Netherlands	Amphia Ziekenhuis	Breda
Netherlands	EB Utrecht	Utrecht
Netherlands	Isala Klinieken	Zwolle
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok	Podlaskie
Poland	NZOZ Mach-Med	Chorzow
Poland	Uniwersyteckie Centrum Kliniczne	Gdansk	Pomorskie
Poland	Klinika Neurologii Neuro-Care	Katowice
Poland	Globe Badania Kliniczne SP Z O.O.	Klodzko
Poland	Prywatny Gabinet Lekarski U.Chyrchel	Lublin
Poland	Centrum Medyczne Medyk	Rzeszow
Poland	Euromedis Sp. z o.o.	Szczecin
Poland	Clinsante Centrum Medyczne	Torun
Poland	Centrum Medyczne	Warszawa
Poland	Specjalistyczny Osrodek Medycyny Wieku Dojrzalego SOMED	Warszawa
Poland	NZOZ Wroclawskie Centrum Alzheimerowskie	Wroclaw	Dolnoslaskie
Portugal	Hospital Fernando Fonseca	Amadora
Portugal	Hospital de Braga	Braga
Portugal	Hospitals da Universidade de Coimbra	Coimbra
Russian Federation	SAIH Republ. Clinical Hospital of the MoH of Republ. Tatarst	Kazan
Russian Federation	SIH Kemerovo Regional Clinical Hosptial	Kemerovo
Russian Federation	FSBIH Siberian Clinical Center of FMBA	Krasnoyarsk
Russian Federation	LLC City Neurological Centre Sibneuromed	Novosibirsk
Russian Federation	Novosibirsk State Medical University	Novosibirsk
Russian Federation	Ultramed	Omsk
Russian Federation	LLC Treatment and Rehabilitation	Rostov-on-Don
Russian Federation	RSBIH Smolensk Regional Clinical Hospital	Smolensk
Russian Federation	Bekhterev Psyconeurological Institute	St. Petersburg
Russian Federation	Central Medical Sanitary Hospital #122	St. Petersburg
Russian Federation	Regional State Institution of Healthcare Tomsk Clinica Psych	Tomsk
Spain	Hospital Ntra Sra Perpetuo Socorro	Albacete
Spain	Fundacion ACE-Institut Catala de Neurociences Aplicades	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Policlinica Guipuzcoa	Donostia	Guipuzcoa
Spain	Hospital Virgen Del Puerto	Plasencia	Caceres
Spain	Hospital Cardiovascular San Vicente	San Vicente del Raspeig	Alicante
Spain	Hospital General de Catalunya	Sant Cugat del Valles	Barcelona
Spain	Hospital Mutua de Terrassa	Terrassa	Barcelona
Spain	Hospital Universitario La Fe de Valencia	Valencia
Taiwan	Changhua Christian Hospital	Changhua
Taiwan	National Taiwan University Hospital	Douliu	Yunlin County
Taiwan	Chang Gung Memorial Hospital - Kaohsiung	Kaohsiung
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taipei Medical University- Shuang Ho Hospital	New Taipei
Taiwan	Cardinal Tien Hospital	Sindian City	Taipei County
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan City
United Kingdom	Charlton Lane Hospital	Cheltenham	Gloucestershire
United Kingdom	Royal Devon and Exeter Hospital	Exeter	Devon
United Kingdom	Glasgow Memory Clinic	Glasgow
United Kingdom	Re-Cognition Health Ltd	Guildford	Surrey
United Kingdom	Re-Cognition Health Ltd	London
United Kingdom	Murray Royal Hospital	Perth	Tayside Region
United Kingdom	Re-Cognition Health Ltd	Plymouth	Devon
United Kingdom	Victoria Centre	Swindon	Wiltshire
United States	Atlanta Center of Medical Research	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	JEM Research Institute	Atlantis	Florida
United States	Georgia Regents University	Augusta	Georgia
United States	American Health Network	Avon	Indiana
United States	Eastern Maine Medical Center	Bangor	Maine
United States	Boston University Medical Center	Boston	Massachusetts
United States	The Research Center of Southern California	Carlsbad	California
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Behavioral Health Center Research	Charlotte	North Carolina
United States	Morton Plant Hospital	Clearwater	Florida
United States	Rapid Medical Research Inc	Cleveland	Ohio
United States	Ericksen Research and Development	Clinton	Utah
United States	Medical Research Health and Education Foundation, Inc	Columbus	Georgia
United States	Ohio State University Medical Center	Columbus	Ohio
United States	The Corvallis Clinic P.C.	Corvallis	Oregon
United States	WCCT Global	Costa Mesa	California
United States	Associated Neurologists, PC - Danbury	Danbury	Connecticut
United States	Brain Matters Research	Delray Beach	Florida
United States	Cohen Medical Associates P.A.	Delray Beach	Florida
United States	Michigan State University	East Lansing	Michigan
United States	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island
United States	University of Kansas Hospital	Fairway	Kansas
United States	Neuropsychiatric Research Center of Southwest Florida	Fort Myers	Florida
United States	Univ of North Texas Health Science Center	Fort Worth	Texas
United States	Neuro-Pain Medical Center	Fresno	California
United States	Neurology Center of North Orange County	Fullerton	California
United States	Radiant Research	Greer	South Carolina
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Indago Research & Health Center, Inc.	Hialeah	Florida
United States	Infinity Clinical Research, LLC	Hollywood	Florida
United States	Hawaii Medical Center	Honolulu	Hawaii
United States	Josephson Wallack Munshower Neurology	Indianapolis	Indiana
United States	Jacksonville Center for Clinical Research	Jacksonville	Florida
United States	Mayo Clinic-Jacksonville	Jacksonville	Florida
United States	Clinical Trial Center, LLC, Psychiatry	Jenkintown	Pennsylvania
United States	NEA Baptist Clinical	Jonesboro	Arkansas
United States	Holston Medical Group Clinical Research	Kingsport	Tennessee
United States	Las Vegas Medical Research	Las Vegas	Nevada
United States	Associates in Neurology, PSC	Lexington	Kentucky
United States	Baptist Health Medical Group	Lexington	Kentucky
United States	SSM Health Dean Medical Group	Madison	Wisconsin
United States	Advanced Clinical Research LLC	Meridian	Idaho
United States	Gregory A. Kirk MD LLC	Merritt Island	Florida
United States	Allied Biomedical Research Institute, Inc.	Miami	Florida
United States	University of Miami	Miami	Florida
United States	American Health Network	Muncie	Indiana
United States	Institute for Neurodegenerative Disorders	New Haven	Connecticut
United States	Yale University School of Medicine	New Haven	Connecticut
United States	New York University Medical Center	New York	New York
United States	Pearl Clinical Research Inc.	Norristown	Pennsylvania
United States	Research Center for Clinical Studies, Inc	Norwalk	Connecticut
United States	Cutting Edge Research Group	Oklahoma City	Oklahoma
United States	Lynn Health Science Institute	Oklahoma City	Oklahoma
United States	Compass Research	Orlando	Florida
United States	Pacific Neuroscience Medical Group	Oxnard	California
United States	St Josephs Hospital and Medical Center	Phoenix	Arizona
United States	Xenoscience	Phoenix	Arizona
United States	Donald S Marks	Plymouth	Massachusetts
United States	Quantum Laboratories	Pompano Beach	Florida
United States	Charlotte Neurological Services	Port Charlotte	Florida
United States	Coastal Neurology PA	Port Royal	South Carolina
United States	Summit Research Network Inc	Portland	Oregon
United States	Butler Hospital	Providence	Rhode Island
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Raleigh Neurology Associates	Raleigh	North Carolina
United States	Clinical Research Professionals	Saint Louis	Missouri
United States	Texas Medical Research Associates, L.L.C.	San Antonio	Texas
United States	California Research Foundation	San Diego	California
United States	Pacific Research Network Inc	San Diego	California
United States	Sharp Mesa Vista Hospital	San Diego	California
United States	Syrentis Clinical Research	Santa Ana	California
United States	Care Access Research	Santa Clarita	California
United States	Intercoastal Medical Group	Sarasota	Florida
United States	Maine Neurology	Scarborough	Maine
United States	Arizona Neurology	Scottsdale	Arizona
United States	Four Peaks Neurology	Scottsdale	Arizona
United States	Insight Clinical Trials	Shaker Heights	Ohio
United States	California Neuroscience Research	Sherman Oaks	California
United States	Axiom Research	Tampa	Florida
United States	University of South Florida	Tampa	Florida
United States	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey
United States	Cotton O'Neil Clinic	Topeka	Kansas
United States	Center for Neurosciences	Tucson	Arizona
United States	Care Access Research	Valencia	California
United States	Neurology Specialists of Monmouth County	West Long Branch	New Jersey
United States	Via Christi Research, Inc.	Wichita	Kansas
United States	Alzheimers Disease Center	Winchester	Massachusetts
United States	PMG Research of Winston-Salem, LLC	Winston-Salem	North Carolina
United States	Wake Forest Baptist Univ CAR	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Mexico,  Netherlands,  Poland,  Portugal,  Russian Federation,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) Score	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, acetylcholinesterase Inhibitor (AChEI) use at baseline, pooled site, and covariates for baseline ADAS-Cog13 total score, age at baseline, and baseline ADAS-Cog13 total score-by-visit interaction.	Baseline, Week 78
Secondary	Change From Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items Score (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, AChEI use at baseline, pooled site, and covariates for baseline iADL score, age at baseline, and baseline iADL score-by-visit interaction.	Baseline, Week 78
Secondary	Change From Baseline in 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 determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline FAQ total score, by-visit interaction and age at baseline.	Baseline, Week 78
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 with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADRS13 total score, age at baseline, and baseline iADRS13 total score-by-visit interaction.	Baseline, Week 78
Secondary	Change From Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score	The CDR-SB is a rater administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which 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, AChEI use at baseline, pooled site, and covariates for baseline CDR-SB score, age at baseline, and baseline CDR-SB score-by-visit interaction.	Baseline, Week 78
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).	From Loss of 1 Global Stage through Week 78
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 a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline NPI score, age at baseline, and baseline NPI score-by-visit interaction.	Baseline, Week 78
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, AChEI use at baseline, pooled site, and covariates for baseline MMSE total score, age at baseline, and baseline MMSE total score-by-visit interaction.	Baseline, Week 78
Secondary	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 71
Secondary	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 71
Secondary	Change From Baseline in CSF Biomarker Total Tau	Cerebrospinal fluid samples were collected for analysis of concentration total tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline.	Baseline, Week 71
Secondary	Change From Baseline in CSF Biomarker Phosphorylated Tau	Cerebrospinal fluid samples are collected for analysis of concentration of phosphorylated tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline.	Baseline, Week 71
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 using ANCOVA methodology with terms for treatment, baseline biomarker and age at baseline.	Baseline, Week 78
Secondary	Change From Baseline in Regional Cerebral Blood Flow (rCBF) Using Florbetapir Perfusion Scan	Florbetapir perfusion evaluated the regional cerebral blood flow (rCBF) as a biomarker of brain function and was performed at the same time as the amyloid florbetapir PET. Cerebral perfusion, especially in temporal and parietal areas, is reduced in AD and this pattern of hypoperfusion closely mirrors the hypometabolism pattern observed using FDG PET. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF (last observation carried forward) and with factors for treatment, baseline biomarker and age at baseline.	Baseline, Week 78
Secondary	Change From Baseline in Whole Brain Volume	Magnetic resonance imaging (MRI) was used to evaluate the effect of lanabecestat on brain atrophy/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 with LOCF and with factors for treatment, baseline volumetric magnetic resonance imaging (vMRI), intracranial volume and age at baseline.	Baseline, Week 78
Secondary	Population Pharmacokinetics (PK): Apparent Oral Clearance of Lanabecestat	The apparent oral clearance of lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis.	Predose, Week 4, 7, 19, 39, 45 and Week 71 post dose
Secondary	Population PK: Central Volume of Distribution of Lanabecestat	The central volume of distribution for lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis.	Predose, Week 4, 7, 19, 39, 45 and week 71 post dose

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