A Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease Dementia

A Randomized, Double-Blind, Delayed-Start Study of LY3314814 (AZD3293) in Early Alzheimer's Disease Dementia (Extension of Study AZES, The AMARANTH Study)

This study is an extension of study I8D-MC-AZES (NCT02245737), the AMARANTH study. The purpose of this study is to evaluate the effectiveness of the study drug lanabecestat in participants with early Alzheimer's disease dementia at the time of entry into study I8D-MC-AZES.

Study Overview

• Status: Terminated
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Lanabecestat

Detailed Description

Study AZFD was designed to be integrated with 104-week study AZES to form a Delayed-Start study (Study AZES-FD). Study AZES-FD was to be used to test the hypothesis that participants originally randomized to receive placebo in the double-blind feeder study AZES and switched to LY3314814 at the start of study AZFD did not "catch up" on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) at Week 26 of study AZFD to participants originally randomized to receive LY3314814 in the double-blind feeder study.

• Study Type: Interventional
• Enrollment (Actual): 421
• Phase: 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
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Clinical Research Unit
    • Glen Iris, Victoria, Australia, 3146
      • Delmont Private 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
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
  • Roeselare, Belgium, 8800
    • AZ DELTA
  • Limburg
    • Hasselt, Limburg, Belgium, 3500
      • Jessa Ziekenhuis
• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 1Z9
      • Okanagan Clinical Trials
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3S1M7
      • True North Clinical Research Halifax, LLC
  • Ontario
    • Ottawa, Ontario, Canada, KIN 5C8
      • Elizabeth Bruyere Health Centre
    • Peterborough, Ontario, Canada, K9H2P4
      • Kawartha Regional Memory Clinic
    • Toronto, Ontario, Canada, M3B 2S7
      • Toronto Memory Program
  • Quebec
    • Gatineau, Quebec, Canada, J8T 8J1
      • Clinique de la Mémoire de l'Outaouais
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • NeuroSearch Developements
    • 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, France, 21079
    • CHU Bocage CMRR
  • Paris, France, 75013
    • Hopital Broca
  • Paris, France, 75013
    • Hôpital de la Pitié-Salpêtrière
  • Paris, France, 75475
    • Hopital Fernand Widal
  • Saint-Herblain, France, 44093
    • CHU de Nantes Hôpital Laennec
  • Toulouse, France, 31052
    • Centre de Recherche Clinique du Gérontopôle Cité de la Santé
  • Villeurbanne, France, 69100
    • Hôpital des charpennes
  • Cedex
    • Lille, Cedex, France, 59037
      • CHRU de Lille- Hópital Roger Salengro
    • Toulouse, Cedex, France, 31059
      • CHU de Toulouse Hopital PURPAN
  • Cedex 05
    • Marseille, Cedex 05, France, 13385
      • Centre Hospitalier Universitaire La Timone
• Germany
  • Berlin, Germany, 10117
    • Charite Universitatsmedizin Berlin
  • Berlin, Germany, 12203
    • Charite Universitatsmedizin Berlin
  • Baden-Württemberg
    • Ulm, Baden-Württemberg, Germany, 89081
      • Universitatsklinikum Ulm
  • Bayern
    • München, Bayern, Germany, 81675
      • Klinikum rechts der Isar der TU Munchen
    • München, Bayern, Germany, 80331
      • Studien und Gedächtniszentrum München
  • Niedersachsen
    • Westerstede, Niedersachsen, Germany, 26655
      • Gemeinschaftspraxis fur Neurologie und Psychiatrie
  • Nordrhein-Westfalen
    • Köln, Nordrhein-Westfalen, Germany, 50937
      • Universitatsklinikum Koln
    • Köln, Nordrhein-Westfalen, Germany, 50935
      • DataMed Klinische Studien GmbH
    • Siegen, Nordrhein-Westfalen, Germany, 57076
      • Neurologische Praxis Siegen
  • Sachsen
    • Mittweida, Sachsen, Germany, 09648
      • Pharm Studienzentrum Chemnitz
• Hungary
  • Budapest, Hungary, 1083
    • SE Neurologiai Klinika
• Japan
  • Fukuoka, Japan, 814-0180
    • Fukuoka University Hospital
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Kyoto, Japan, 616-8255
    • Utano Hospital
  • Osaka, Japan, 637086
    • Osaka City University Hospital
  • Aichi
    • Obu, Aichi, Japan, 474-0038
      • National Institute for Longevity Sciences NCGG
  • Chiba
    • Chuo-ku, Chiba, Japan, 260-8712
      • National Chiba-East-Hospital
  • Ibaraki
    • Tsukuba, Ibaraki, Japan, 305-8576
      • Tsukuba University Hospital
  • Iwate
    • Morioka, Iwate, Japan, 020-8505
      • Iwate Medical University Hospital
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 210-0852
      • Nihon Kokan Hospital
  • Okayama
    • Kurashiki, Okayama, Japan, 701-0192
      • KATAYAMA medical Clinic
  • Okinawa
    • Urasoe, Okinawa, Japan, 901-2102
      • Shiroma Clinic
  • Osaka
    • Sakai, Osaka, Japan, 593-8301
      • Sakaguchi Clinic
    • Toyonaka, Osaka, Japan, 560-8552
      • National Sanatorium Toneyama Hospital
  • Tokyo
    • Bunkyo-Ku, Tokyo, Japan, 113-8603
      • Nippon Medical School Hospital
    • Bunkyo-ku, Tokyo, Japan, 113-8655
      • The University of Tokyo Hospital
    • Bunkyo-ku, Tokyo, Japan, 113-0034
      • Memory Clinic Ochanomizu
    • Shinjuku-ku, Tokyo, Japan, 162-8666
      • Tokyo Women's Medical University Hospital
  • Toyama
    • Nanto, Toyama, Japan, 939-1893
      • National Sanatorium Hokuriku Hospital
• Korea, Republic of
  • Incheon, Korea, Republic of, 21565
    • Gachon University Gil Medical Center
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06591
    • Seoul st. mary's hospital
  • Busan
    • Seogu, Busan, Korea, Republic of, 49201
      • Dong-A University Medical Center
  • Gyeonggido
    • Guri-si, Gyeonggido, Korea, Republic of, 11923
      • Hanyang University Guri Hospital
  • Incheon
    • Junggu, Incheon, Korea, Republic of, 22332
      • Inha University Hospital
  • Korea
    • Seoul, Korea, Korea, Republic of, 06351
      • Samsung Medical Center
• Poland
  • Bydgoszcz, Poland, 85-796
    • NZOZ Dom Sue Ryder - Pallmed Sp. z o.o.
  • Katowice, Poland, 40-123
    • NZOZ Wielospecjalistyczna Poradnia Lekarska
  • Kielce, Poland, 25-411
    • Centrum Zdrowia Psychicznego Biomed - Jan Latala
  • Krakow, Poland, 31-505
    • Krakowska Akademia Neurologii
  • Lodz, Poland, 93-118
    • Medycyna Milorzab
  • Lublin, Poland, 20-950
    • Instytut Medycyny Wsi
  • Warszawa, Poland, 01-697
    • Centrum Medyczne NeuroProtect
  • Podlaskie
    • Białystok, Podlaskie, Poland, 15-732
      • Podlaskie Centrum Psychogeriatrii
• Puerto Rico
  • Bayamón, Puerto Rico, 00961-6911
    • Santa Cruz Behavioral PSC
• Romania
  • Bucuresti, Romania, 010719
    • SC Med Life SA
  • Bucuresti, Romania, 011025
    • SC Centrul Medical Sana SRL
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic i Provincial
  • Barcelona, Spain, 08025
    • Hospital Santa Creu i Sant Pau
  • Barcelona, Spain, 08014
    • Fundacion ACE-Institut Catala de Neurociences Aplicades
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon Y Cajal
  • Madrid, Spain, 28006
    • Hospital de La Princesa
  • Palma De Mallorca, Spain, 07010
    • Hospital Son Espases
  • Valencia, Spain, 46026
    • Hospital Universitario La Fe de Valencia
  • Valencia, Spain, 46017
    • Hospital Universitario Dr Pesset
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Hospital Universitari de Bellvitge
  • Caceres
    • Plasencia, Caceres, Spain, 10600
      • Hospital Virgen del Puerto
  • Getafe
    • Madrid, Getafe, Spain, 28905
      • Hospital Universitario de Getafe
  • Guipuzcoa
    • San Sebastian, Guipuzcoa, Spain, 20009
      • CITA Alzheimer
  • Vizcaya
    • Getxo, Vizcaya, Spain, 48993
      • Centro de Atencion Especializada (CAE) OROITU
• United Kingdom
  • Glasgow, United Kingdom, G20 0XA
    • Glasgow Memory Clinic
  • Leeds, United Kingdom, LS10 1DU
    • MAC Clinical Research
  • Greater London
    • London, Greater London, United Kingdom, W1G 9JF
      • Re-Cognition Health Ltd
  • Greater Manchester
    • Manchester, Greater Manchester, United Kingdom, M13 9NQ
      • MAC Clinical Research-Manchester
  • Lancashire
    • Blackpool, Lancashire, United Kingdom, FY2 0JH
      • MAC Clinical Research
  • London
    • Isleworth, London, United Kingdom, TW7 6FY
      • West London Mental Health NHS Trust
  • Staffordshire
    • Cannock, Staffordshire, United Kingdom, WS11 0BN
      • MAC Clinical Research
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7YD
      • Re-Cognition Health Ltd
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner Alzheimer's Institute
    • Tucson, Arizona, United States, 85704
      • Territory Neurology & Research Institute
  • California
    • San Diego, California, United States, 92103
      • Pacific Research Network Inc
  • 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
    • 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
    • West Palm Beach, Florida, United States, 33407
      • Premiere Research Institute at Palm Beach Neurology
  • Georgia
    • Atlanta, Georgia, United States, 30327
      • The Multiple Sclerosis Center of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Anderson, Indiana, United States, 46011
      • Community Clinical Research Center
  • Massachusetts
    • Newton, Massachusetts, United States, 02459
      • Boston Center for Memory
  • Mississippi
    • Hattiesburg, Mississippi, United States, 39401
      • Hattiesburg Clinic
  • New Jersey
    • Eatontown, New Jersey, United States, 07724
      • Memory Enhancement Center of America, Inc.
    • 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
  • New York
    • Brooklyn, New York, United States, 11229
      • Integrative Clinical Trials, LLC
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14620
      • University of Rochester School of Medicine
  • Ohio
    • Centerville, Ohio, United States, 45459
      • Valley Medical Primary Care
    • Cincinnati, Ohio, United States, 45219
      • Lindner Research Center
    • Columbus, Ohio, United States, 43210
      • Ohio State University Medical Center
  • 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
    • Greer, South Carolina, United States, 29651
      • Radiant Research
  • Tennessee
    • Johnson City, Tennessee, United States, 37604
      • Quillen College of Medicine, East TN State University
  • Vermont
    • Bennington, Vermont, United States, 05201
      • The Memory Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 53 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants previously enrolled in AMARANTH (NCT02245737) who meet eligibility criteria for delayed-start I8D-MC-AZFD.

Exclusion Criteria:

• Participants who participate in AMARANTH (NCT02245737) who develop new conditions precluding them from enrolling into I8D-MC-AZFD.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AZES Lanabecestat 20 milligrams (mg)/AZFD Lanabecestat 20 mg; Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.	Drug: Lanabecestat; Administered orally; Other Names: LY3314814; AZD3293
Experimental: AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg; Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.	Drug: Lanabecestat; Administered orally; Other Names: LY3314814; AZD3293
Experimental: AZES Placebo/AZFD Lanabecestat 20 mg; Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.	Drug: Lanabecestat; Administered orally; Other Names: LY3314814; AZD3293
Experimental: AZES Placebo/AZFD Lanabecestat 50 mg; Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.	Drug: Lanabecestat; Administered orally; Other Names: LY3314814; AZD3293

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline Analysis 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*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, apolipoprotein E4 (APOE4) status, acetylcholinesterase inhibitor (AChEI) use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline Analysis 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 with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
Change From Baseline on the Functional Activities Questionnaire (FAQ) Score	FAQ is a 10-item, caregiver-questionnaire and was administered to the study partner and 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 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 determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
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*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
Change From Baseline on the Mini-Mental Status Examination (MMSE)	The MMSE is an instrument used to assess a participant's 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*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
Change From Baseline Analysis on the ADAS-Cog13	ADAS-cog13 (13-item 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*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 52

Collaborators and Investigators

• Sponsor: AstraZeneca
• Collaborators: Eli Lilly and Company

Publications and helpful links

Helpful Links

• Click here for more information about this study: A Study of LY3314814 in Early Alzheimer's Disease Dementia
• CSP
• SAP

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2017
• Primary Completion (Actual): October 2, 2018
• Study Completion (Actual): October 2, 2018

Study Registration Dates

• First Submitted: November 21, 2016
• First Submitted That Met QC Criteria: November 21, 2016
• First Posted (Estimate): November 23, 2016

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Alzheimer's Disease; Nervous System Diseases; Dementia; Memory; Central Nervous System Diseases; Neurodegenerative Diseases; Mental Disorders; Brain Diseases; Delirium, Dementia, Amnestic, Cognitive Disorders; Amyloid; Tauopathies
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Tauopathies; Dementia; Alzheimer Disease
• Other Study ID Numbers: 16557; I8D-MC-AZFD (Other Identifier: Eli Lilly and Company); 2016-003440-36 (EudraCT Number)

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)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No