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

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)

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.

Study Overview

• Status: Terminated
• Conditions: Alzheimer´s Disease
• Intervention / Treatment: Drug: Placebo; Drug: Lanabecestat

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 2218
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Noble Park, Australia, 3174
    • Neuro Trials Victoria Pty Ltd
  • New South Wales
    • Kogarah, New South Wales, Australia, 2217
      • Southern Neurology
  • Queensland
    • Gold Coast, Queensland, Australia, 4222
      • Griffith University
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Glen Iris, Victoria, Australia, 3146
      • Delmont Private Hospital
    • Heidelberg, Victoria, Australia, 3081
      • Heidelberg Repatriation Hospital
    • Parkville, Victoria, Australia, 3052
      • The Florey Institute of Neuroscience and Mental Health
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Australian Alzheimer's Research Foundation
• Belgium
  • Brussel, Belgium, 1070
    • Hospital Universitaire Erasme Brussel
  • Brussels, Belgium, 1200
    • Cliniques universitaires Saint-Luc
  • Brussels, Belgium, 1020
    • Hopital Universitaire Brugmann Brussel
  • Edegem, Belgium, 2650
    • Universitair Ziekenhuis Antwerpen
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Roeselare, Belgium, 8800
    • Heilig Hartziekenhuis
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Jessa Ziekenhuis
• Canada
  • British Columbia
    • Kamloops, British Columbia, Canada, V2C 1K7
      • The Medical Arts Health Research Group
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Okanagan Clinical Trials
    • Vancouver, British Columbia, Canada, V6T 2B5
      • University of British Columbia
    • Victoria, British Columbia, Canada, V8R 158
      • Royal Jubilee Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S1M7
      • True North Clinical Research Halifax, LLC
  • Ontario
    • Ottawa, Ontario, Canada, K1N 5C8
      • Bruyere Continuing Care
    • Peterborough, Ontario, Canada, K9H2P4
      • Kawartha Regional Memory Clinic
    • Toronto, Ontario, Canada, M5T2S8
      • Toronto Western Hospital
    • Toronto, Ontario, Canada, M3B2S7
      • Toronto Memory Program
  • Qubec
    • Sherbrooke, Qubec, Canada, J1J3H5
      • CSSS-Institut Universitaire Gériatric de Sherbrooke
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Clinique de la Mémoire de l'Outaouais
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • NeuroSearch Developements
    • Montreal, Quebec, Canada, H1T 2M4
      • Hopital Maisonneure-Rosemount
    • Quebec City, Quebec, Canada, G1J 1Z4
      • Hopital de L'enfant Jesus
    • Sherbrooke, Quebec, Canada, J1J 2G2
      • Q&T Research Sherbrooke Inc
• France
  • Bron Cedex, France, 69677
    • Hopital Neuro Pierre Wertheimer
  • Dijon Cedex, France, 21033
    • CHU Dijonon
  • Lille Cedex, France, 59037
    • CHRU Lille - Hôpital Roger Salengro
  • Marseille Cedex 05, France, 13385
    • CHU Hôpital de la Timone
  • Nantes, France, 44093
    • CHU de Nantes Hôpital Laennec
  • Paris, France, 75013
    • Hôpital Broca
  • Paris, France, 75013
    • Hopital de la Pitie Salpetriere
  • Paris, France, 75475
    • Hopital Lariboisiere
  • Toulouse, France, 31052
    • CHU de Toulouse
  • Villeurbanne, France, 69100
    • Hôpital des charpennes
  • Cedex 9
    • Toulouse, Cedex 9, France, 31059
      • CHU de Toulouse Hopital PURPAN
• Germany
  • Berlin, Germany, 13353
    • Charite Universitatsmedizin Berlin
  • Berlin, Germany, 12203
    • Charite Universitatsmedizin Berlin
  • Berlin, Germany, 12163
    • Gemeinschaftspraxis Dr. R. Ehret & Dr. W. von Pannwitz
  • Baden-Württemberg
    • Tübingen, Baden-Württemberg, Germany, 72076
      • Universitätsklinikum Tübingen
    • Ulm, Baden-Württemberg, Germany, 89081
      • Universitätsklinikum Ulm
  • Bayern
    • München, Bayern, Germany, 81675
      • Klinikum rechts der Isar der TU München
    • München, Bayern, Germany, 80331
      • Studien und Gedächtniszentrum München
    • Nürnberg, Bayern, Germany, 90402
      • Institut fur Psychogerontologie
    • Prien am Chiemsee, Bayern, Germany, 83209
      • Neurozentrum Prien
    • Wenzenbach, Bayern, Germany, 93173
      • Institut für Neuropsychiatrie INP3
  • Niedersachsen
    • Westerstede, Niedersachsen, Germany, 26655
      • Studienzentrum Nord-West
  • Nordrhein-Westfalen
    • Bochum, Nordrhein-Westfalen, Germany, 44787
      • Praxis Dr. Lauter
    • Bochum, Nordrhein-Westfalen, Germany, 44791
      • St Josef-Hospital Bochum
    • Bonn, Nordrhein-Westfalen, Germany, 53105
      • Universitätsklinikum Bonn
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Universitatsklinikum Koln
    • Köln, Nordrhein-Westfalen, Germany, 50935
      • Gemeinschaftspraxis für Neurologie Prof. Gereon Nelles
    • Siegen, Nordrhein-Westfalen, Germany, 57076
      • Neurologische Praxis Siegen
  • Saarland
    • Homburg, Saarland, Germany, 66421
      • Universitätsklinikum des Saarlandes
  • Sachsen
    • Mittweida, Sachsen, Germany, 09648
      • Pharmakologisches Studienzentrum Chemnitz
  • Sachsen-Anhalt
    • Halle (Saale), Sachsen-Anhalt, Germany, 06097
      • Martin-Luther-Universität Halle-Wittenberg
    • Magdeburg, Sachsen-Anhalt, Germany, 39120
      • Universitätsklinikum Otto-von-Guericke-Universität
  • Thüringen
    • Gera, Thüringen, Germany, 07551
      • Arztpraxis Dr. Christian Oehlwein
• Hungary
  • Budapest, Hungary, 1097
    • Del-pesti Centrumkorhaz - Orszagos Hematologiai es Infektologiai Intezet
  • Budapest, Hungary, 1083
    • Semmelweis Medical University
  • Debrecen, Hungary, 4032
    • Debreceni Egyetem Klinikai Központ
  • Debrecen, Hungary, 4031
    • Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz
  • Szeged, Hungary, 6725
    • Univerisity of Szeged
  • Baranya
    • Pecs, Baranya, Hungary, 7623
      • PTE KK Pszichiatriai es Pszichoterapias Klinika
• Italy
  • Ancona, Italy, 60126
    • Università Politecnica delle Marche Torrette
  • Brescia, Italy, 25125
    • IRCCS San Giovanni Di Dio Fatebenefratelli
  • Chieti, Italy, 66100
    • Fondazione Universitaria degli Studi G D'Annunzio
  • Genova, Italy, 16132
    • Ente Ospedaliero Ospedali Galliera
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca'Granda Ospedale Maggiore Policinico
  • Modena, Italy, 41010
    • Nuovo Ospedale Civile Sant'Agostino Estense
  • Roma, Italy, 00168
    • Policlinico Univ. Agostino Gemelli
  • Roma, Italy, 00186
    • Ospedale San Giovanni Calibita Fatebenefratelli
  • Roma, Italy, 00189
    • Policlinico Ospedale S. Andrea
  • Roma, Italy, 00185
    • Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
  • Torino, Italy, 10126
    • Azienda Ospedaliera Citta della Salute della Scienza Torino
  • Biella
    • Ponderano, Biella, Italy, 13875
      • Ospedale Degli Infermi ASR USSL 12
  • Milano
    • Monza, Milano, Italy, 20900
      • Azienda Ospedaliera San Gerardo
  • PI
    • Pisa, PI, Italy, 56126
      • Università di Pisa
  • Palermo
    • Cefalu, Palermo, Italy, 90015
      • Fondazione San Raffaele Giglio di Cefalu
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Kyoto, Japan, 616-8255
    • Utano Hospital
  • Kyoto, Japan, 610-0113
    • Kyoto Minami Hospital
  • Osaka, Japan, 545-8586
    • 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.
  • Aichi
    • Obu, Aichi, Japan, 474-0038
      • National Institute for Longevity Sciences NCGG
  • Chiba
    • Chuo-ku, Chiba, Japan, 260-8712
      • National Chiba-East-Hospital
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 070-8644
      • National Hospital Organization Asahikawa Medical Center
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-8576
      • Tsukuba University Hospital
  • Iwate
    • Morioka, Iwate, Japan, 020-8505
      • Iwate Medical University Hospital
  • Kanagawa
    • Kamakura, Kanagawa, Japan, 247-8533
      • Shonan Kamakura General Hospital
    • Kawasaki, Kanagawa, Japan, 210-0852
      • Nihon Kokan Hospital
    • Yokohama, Kanagawa, Japan, 236-0004
      • Yokohama City University Hospital
  • Kyoto
    • Kyoto-shi, Kyoto, Japan, 602-8566
      • Kyoto Prefectural University of Medicine
    • Kyoto-shi, Kyoto, Japan, 607-8113
      • Rakuwakai Otowarehabilitation Hospital
  • Nagano
    • Ina, Nagano, Japan, 396-8555
      • Ina Central Hospital
    • Matsumoto, Nagano, Japan, 399-0021
      • Matsumoto Medical Center
  • Okayama
    • Kurashiki, Okayama, Japan, 701-0192
      • Katayama Medical Clinic
  • Okinawa
    • Urasoe, Okinawa, Japan, 901-2102
      • Shiroma Clinic
  • Osaka
    • Ibaraki, Osaka, Japan, 567-0011
      • Koshokai aino hospital
    • Sakai, Osaka, Japan, 593-8301
      • Sakaguchi Clinic
    • Toyonaka, Osaka, Japan, 560-8552
      • National Sanatorium Toneyama Hospital
  • Saitama
    • Iruma-Gun, Saitama, Japan, 350-0495
      • Saitama Medical University Hospital
  • Tokyo
    • Bunkyo-Ku, Tokyo, Japan, 113-8603
      • Nippon Medical School Hospital
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • The University of Tokyo Hospital
    • Mitaka-shi, Tokyo, Japan, 181-0013
      • Nozomi Memory Clinic
    • Setagaya, Tokyo, Japan, 154-0004
      • Sangenjaya Nakamura Mental Clinic
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Tokyo Women's Medical University Hospital
    • Shinjuku-ku, Tokyo, Japan, 160-0023
      • Kanauchi Medical Clinic
    • Tsukuba, Tokyo, Japan, 305 8576
      • Memory Clinic Ochanomizu
  • Toyama
    • Nanto, Toyama, Japan, 939-1893
      • National Sanatorium Hokuriku Hospital
• Korea, Republic of
  • Incheon, Korea, Republic of, 22332
    • Inha University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul St. Mary's Hospital
  • Busan
    • Seogu, Busan, Korea, Republic of, 49201
      • Dong-A University Medical Center
  • Geonggi-do
    • Seongnam-si, Geonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
  • Gyeonggi-do
    • Bucheon-si, Gyeonggi-do, Korea, Republic of, 14647
      • The Catholic University of Korea-Bucheon St. Mary's Hospital
  • Gyeonggido
    • Guri-si, Gyeonggido, Korea, Republic of, 11923
      • Hanyang University Guri Hospital
  • Incheon
    • Namdong, Incheon, Korea, Republic of, 21565
      • Gachon University Gil Medical Center
• Poland
  • Bydgoszcz, Poland, 85-796
    • NZOZ Dom Sue Ryder - Pallmed Sp. z o.o.
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska
  • Katowice, Poland, 40-588
    • Specjalistyczna Praktyka Lekarska prof. Grzegorz Opala
  • Kielce, Poland, 25411
    • Centrum Zdrowia Psychicznego
  • Krakow, Poland, 31-505
    • Centrum Neurologii Klinicznej
  • Lublin, Poland, 20-064
    • NZOZ Neuromed M. i M. Nastaj Sp. P.
  • Lublin, Poland, 20-090
    • Instytut Medycyny Wsi
  • Siemianowice Śląskie, Poland, 41-100
    • Neuro-Care Sp. z o.o. Sp. Komandytowa
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny MSW
  • Warszawa, Poland, 01-697
    • Centrum Medyczne
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 53 139
      • NZOZ Wroclawskie Centrum Alzheimerowskie
  • Lódzkie
    • Lodz, Lódzkie, Poland, 92216
      • Medycyna Milorzab
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-732
      • Podlaskie Centrum Psychogeriatrii
• Puerto Rico
  • Bayamon, Puerto Rico, 00961
    • Santa Cruz Behavioral PSC
  • Carolina, Puerto Rico, 00984
    • Ivonne Z. Jimenez-Velazquez, MD
  • San Juan, Puerto Rico, 00918
    • Instituto De Neurologia Dra. Ivonne Fraga
  • San Juan, Puerto Rico, 00918
    • Michel A. Woodbury-Farina, MD.
• Romania
  • Bucuresti, Romania, 010719
    • SC Med Life SA
  • Bucuresti, Romania, 011025
    • SC Centrul Medical Sana SRL
  • Bucuresti, Romania, 30463
    • Policlinica CCBR S.R.L.
  • Timisoara, Romania, 300166
    • SC Med Life SA
• Spain
  • Barcelona, Spain, 08003
    • Hospital del Mar
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08025
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain, 08907
    • Hospital Universitari de Bellvitge
  • Barcelona, Spain, 08028
    • Fundacion ACE-Institut Catala de Neurociences Aplicades
  • Cordoba, Spain, 14004
    • Hospital Reina Sofía
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28006
    • Hospital de La Princesa
  • Palma de Mallorca, Spain, 07010
    • Hospital Son Espases
  • Reus, Spain, 43204
    • Hospital Univ Sant Joan de Reus, S.A.
  • San Sebastian, Spain, 20009
    • Fundacion CITA alzheimer
  • Valencia, Spain, 46017
    • Hospital Doctor Peset
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe de Valencia
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche
  • Barcelona
    • Sant Cugat del Valles, Barcelona, Spain, 08190
      • Hospital General de Catalunya
  • Caceres
    • Plasencia, Caceres, Spain, 10600
      • Hospital Virgen del Puerto
  • Getafe
    • Madrid, Getafe, Spain, 28905
      • Hospital Universitario de Getafe
  • Madrid
    • Majadahonda, Madrid, Spain, 28222
      • Hospital Puerta de Hierro
  • Vizcaya
    • Getxo, Vizcaya, Spain, 48993
      • Centro de Atencion Especializada (CAE) OROITU
• United Kingdom
  • Brentford, United Kingdom, TW8 8DS
    • West London Mental Health NHS Trust
  • Glasgow, United Kingdom, G20 0XA
    • Glasgow Memory Clinic
  • London, United Kingdom, W12 0NN
    • Hammersmith Hospital
  • London, United Kingdom, W1G 9JF
    • Guildford Nuffield Hospital
  • London, United Kingdom, W1G 9RU
    • Re-Cognition Health Ltd
  • Manchester, United Kingdom, M13 9NQ
    • MAC Clinical Research
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8BX
      • Plymouth Hospitals NHS Trust
  • East Sussex
    • Crowborough, East Sussex, United Kingdom, TN6 1HB
      • Cognitive Treatment & Research Unit
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO30 3JB
      • Southern Health NHS
  • Lancs
    • Blackpool, Lancs, United Kingdom, FY20JH
      • MAC UK Neuroscience Ltd
  • Leeds
    • Stourton, Leeds, United Kingdom, LS10 1DU
      • MAC Clinical Research
  • Staffordshire
    • Cannock, Staffordshire, United Kingdom, WS11 0BN
      • MAC Clinical Research
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Phoenix, Arizona, United States, 85013
      • St Josephs Hospital and Medical Center
    • Sun City, Arizona, United States, 85351
      • Banner Sun Health Research Institute
    • Tucson, Arizona, United States, 85704
      • Territory Neurology & Research Institute
  • California
    • Fremont, California, United States, 94538
      • Positron Research International
    • Laguna Hills, California, United States, 92653
      • Senior Clinical Trials, Inc.
    • Laguna Hills, California, United States, 92653
      • Alliance Research Centers
    • Long Beach, California, United States, 90806
      • Collaborative Neuroscience Network - CNS
    • San Diego, California, United States, 92103
      • Pacific Research Network Inc
    • San Francisco, California, United States, 94109
      • San Francisco Clinical Research Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Mile High Research Center
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Institute for Neurodegenerative Disorders
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University Medical Center
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Brain Matters Research
    • Hialeah, Florida, United States, 33012
      • Direct Helpers Medical Center
    • Hialeah, Florida, United States, 33016
      • Galiz Research
    • Hialeah, Florida, United States, 33016
      • Berma Research
    • Hialeah, Florida, United States, 33018
      • Maxblue Institute
    • Lake Worth, Florida, United States, 33449
      • Alzheimer's Research and Treatment Center
    • Miami, Florida, United States, 33144
      • Medical Research Center
    • Miami, Florida, United States, 33175
      • New Horizon Research Center
    • Miami, Florida, United States, 33137
      • Miami Jewish Health Systems
    • Miami, Florida, United States, 33155
      • Allied Biomedical Research Institute, Inc.
    • Miami, Florida, United States, 33174
      • Advance Medical Research Institute
    • Miami, Florida, United States, 33186
      • JDH Medical Group, LLC
    • Orlando, Florida, United States, 32806
      • Compass Research
    • Palmetto Bay, Florida, United States, 33157
      • IMIC, Inc.
    • Saint Petersburg, Florida, United States, 33713
      • Suncoast Neuroscience Associates
    • Sarasota, Florida, United States, 34243
      • Roskamp Institute
    • Sunrise, Florida, United States, 33351
      • Infinity Clinical Research, LLC
    • Tampa, Florida, United States, 33613
      • Stedman Clinical Trials
    • Tampa, Florida, United States, 33614
      • Olympian Clinical Research
    • The Villages, Florida, United States, 32162
      • Compass Research
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute at Palm Beach Neurology
  • Georgia
    • Atlanta, Georgia, United States, 30331
      • Atlanta Center of Medical Research
    • Atlanta, Georgia, United States, 30327
      • The Multiple Sclerosis Center of Atlanta
    • Smyrna, Georgia, United States, 30080
      • Carman Research
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Elk Grove Village, Illinois, United States, 60007
      • Alexian Brothers Medical Center
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Community Clinical Research Center
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Massachusetts
    • Methuen, Massachusetts, United States, 01844
      • ActivMed Practices & Research, Inc
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
    • Springfield, Massachusetts, United States, 01104
      • Springfield Neurology Associates
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • St. Louis Clinical Trials, LC
    • Saint Louis, Missouri, United States, 63141
      • Millennium Psychiatric Associates, LLV
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America, Inc.
    • Lawrenceville, New Jersey, United States, 08648
      • AdvanceMed Research
    • Manchester, New Jersey, United States, 08759
      • Alzheimer's Research Company
    • Springfield, New Jersey, United States, 07081
      • The Cognitive and Research Center of NJ
    • Toms River, New Jersey, United States, 08755
      • Advanced Memory Research Institute of New Jersey
    • Toms River, New Jersey, United States, 08755
      • Bio Behavioral Health
    • West Long Branch, New Jersey, United States, 07764
      • Neurology Specialists of Monmouth County
  • New York
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials, LLC
    • Brooklyn, New York, United States, 11235
      • SPRI Clinical Trials, LLC.
    • Buffalo, New York, United States, 14203
      • Alzheimer's Disease and Memory Disorders Center
    • Latham, New York, United States, 12110
      • Empire Neurology, PC
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10019
      • Clinilabs, Inc (New York)
    • Rochester, New York, United States, 14620
      • University of Rochester
  • North Carolina
    • Charlotte, North Carolina, United States, 28270
      • Alzheimer's Memory Center
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Valley Medical Primary Care
    • Cincinnati, Ohio, United States, 45219
      • Christ Hospital
    • Columbus, Ohio, United States, 43221
      • Ohio State University Medical Center
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • The Corvallis Clinic P.C.
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Hospital
  • Rhode Island
    • East Providence, Rhode Island, United States, 02914
      • Rhode Island Mood & Memory Research Institute
  • South Carolina
    • Charleston, South Carolina, United States, 29401
      • Roper St. Francis Healthcare
    • Greer, South Carolina, United States, 29651
      • Radiant Research
  • Tennessee
    • Johnson City, Tennessee, United States, 37605
      • Quillen College of Medicine, East TN State University
  • Texas
    • Austin, Texas, United States, 78757
      • Senior Adults Specialty Research Inc
    • Dallas, Texas, United States, 75231
      • Texas Health Physicians Group
    • Fort Worth, Texas, United States, 76104
      • Medical Group of Texas
    • Houston, Texas, United States, 77054
      • University of Texas Health Services Center - Houston
  • Utah
    • Salt Lake City, Utah, United States, 84108
      • University of Utah School of Medicine
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lanabecestat 20 milligrams (mg); Lanabecestat 20 mg given orally once daily for 104 weeks.	Drug: Lanabecestat; Administered orally; Other Names: LY3314814; AZD3293
Experimental: Lanabecestat 50 mg; Lanabecestat 50 mg given orally once daily for 104 weeks.	Drug: Lanabecestat; Administered orally; Other Names: LY3314814; AZD3293
Placebo Comparator: Placebo; Placebo given orally once daily for 104 weeks.	Drug: Placebo; Administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
Pharmacodynamics (PD): Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42	Concentration of the peptide Aβ 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
PD: Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40	Concentration of the peptide Aβ 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
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
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
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
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
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
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
Pharmacokinetics (PK): Plasma Concentration of Lanabecestat		Week 4, post dose prior to departure from the clinic

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company

Publications and helpful links

General Publications

• Wessels AM, Lines C, Stern RA, Kost J, Voss T, Mozley LH, Furtek C, Mukai Y, Aisen PS, Cummings JL, Tariot PN, Vellas B, Dupre N, Randolph C, Michelson D, Andersen SW, Shering C, Sims JR, Egan MF. Cognitive outcomes in trials of two BACE inhibitors in Alzheimer's disease. Alzheimers Dement. 2020 Nov;16(11):1483-1492. doi: 10.1002/alz.12164. Epub 2020 Oct 13.
• Wessels AM, Tariot PN, Zimmer JA, Selzler KJ, Bragg SM, Andersen SW, Landry J, Krull JH, Downing AM, Willis BA, Shcherbinin S, Mullen J, Barker P, Schumi J, Shering C, Matthews BR, Stern RA, Vellas B, Cohen S, MacSweeney E, Boada M, Sims JR. Efficacy and Safety of Lanabecestat for Treatment of Early and Mild Alzheimer Disease: The AMARANTH and DAYBREAK-ALZ Randomized Clinical Trials. JAMA Neurol. 2020 Feb 1;77(2):199-209. doi: 10.1001/jamaneurol.2019.3988. Erratum In: JAMA Neurol. 2020 Sep 1;77(9):1179.
• Cebers G, Alexander RC, Haeberlein SB, Han D, Goldwater R, Ereshefsky L, Olsson T, Ye N, Rosen L, Russell M, Maltby J, Eketjall S, Kugler AR. AZD3293: Pharmacokinetic and Pharmacodynamic Effects in Healthy Subjects and Patients with Alzheimer's Disease. J Alzheimers Dis. 2017;55(3):1039-1053. doi: 10.3233/JAD-160701.

Helpful Links

• Click here for more information about this study: An Efficacy and Safety Study of LY3314814 in Early Alzheimer's Disease
• CSP
• SAP

Study record dates

Study Major Dates

• Study Start (Actual): September 30, 2014
• Primary Completion (Actual): October 4, 2018
• Study Completion (Actual): October 4, 2018

Study Registration Dates

• First Submitted: September 18, 2014
• First Submitted That Met QC Criteria: September 18, 2014
• First Posted (Estimate): September 22, 2014

Study Record Updates

• Last Update Posted (Actual): December 3, 2019
• Last Update Submitted That Met QC Criteria: November 19, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Alzheimer's disease; Nervous System Diseases; Dementia; Central Nervous System Diseases; Mental Disorders; Brain Diseases; Delirium, Dementia, Amnestic, Cognitive Disorders; Tauopathies; Neurogenerative Diseases
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: 16023; I8D-MC-AZES (Other Identifier: Eli Lilly and Company); 2014-002601-38 (EudraCT Number); D5010C00009 (Other Identifier: AstraZeneca)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
• IPD Sharing Time Frame: Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)