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

• ClinicalTrials.gov Identifier: NCT02245737
• Recruitment Status: Terminated
• First Posted: September 22, 2014
• Results First Posted: August 6, 2019
• Last Update Posted: December 3, 2019
• Sponsor: AstraZeneca
• Collaborator: Eli Lilly and Company
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Alzheimer´s Disease	Drug: Lanabecestat; Drug: Placebo	Phase 2; Phase 3

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 2218 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A 24-month, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy, Safety, Tolerability, Biomarker, and Pharmacokinetic Study of AZD3293 in Early Alzheimer's Disease (The AMARANTH Study)
• Actual Study Start Date: September 30, 2014
• Actual Primary Completion Date: October 4, 2018
• Actual Study Completion Date: October 4, 2018

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) [ Time Frame: Baseline, Week 104 ]
   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.

Secondary Outcome Measures :

1. Change From Baseline on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL) [ Time Frame: Baseline, Week 104 ]
   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.
2. Change From Baseline on the Functional Activities Questionnaire (FAQ) Score [ Time Frame: Baseline, Week 104 ]
   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.
3. Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score [ Time Frame: Baseline, Week 104 ]
   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.
4. Change From Baseline on the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score [ Time Frame: Baseline, Week 104 ]
   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.
5. Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage [ Time Frame: Baseline through Loss of 1 Global Stage or Week 104 ]
   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).
6. Change From Baseline in Neuropsychiatric Inventory (NPI) Score [ Time Frame: Baseline, Week 104 ]
   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.
7. Change From Baseline on the Mini-Mental State Examination (MMSE) [ Time Frame: Baseline, Week 104 ]
   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.
8. Pharmacodynamics (PD): Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42 [ Time Frame: Baseline, Week 97 ]
   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.
9. PD: Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40 [ Time Frame: Baseline, Week 97 ]
   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.
10. Change From Baseline in CSF Total Tau [ Time Frame: Baseline, Week 97 ]
    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.
11. Change From Baseline in CSF Phosphorylated Tau [ Time Frame: Baseline, Week 97 ]
    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.
12. Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan [ Time Frame: Baseline, Week 104 ]
    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.
13. Change From Baseline in Tau PET ((Flortaucipir F18) [ Time Frame: Baseline, Week 104 ]
    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.
14. Change From Baseline in Brain Metabolism Using Fluorodeoxyglucose (FDG) [ Time Frame: Baseline, Week 104 ]
    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.
15. Change From Baseline in Whole Brain Volume [ Time Frame: Baseline, Week 104 ]
    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.
16. Pharmacokinetics (PK): Plasma Concentration of Lanabecestat [ Time Frame: Week 4, post dose prior to departure from the clinic ]

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, Arizona

Banner Alzheimer's Institute

Phoenix, Arizona, United States, 85006

St Josephs Hospital and Medical Center

Phoenix, Arizona, United States, 85013

Banner Sun Health Research Institute

Sun City, Arizona, United States, 85351

Territory Neurology & Research Institute

Tucson, Arizona, United States, 85704

United States, California

Positron Research International

Fremont, California, United States, 94538

Alliance Research Centers

Laguna Hills, California, United States, 92653

Senior Clinical Trials, Inc.

Laguna Hills, California, United States, 92653

Collaborative Neuroscience Network - CNS

Long Beach, California, United States, 90806

Pacific Research Network Inc

San Diego, California, United States, 92103

San Francisco Clinical Research Center

San Francisco, California, United States, 94109

United States, Colorado

Mile High Research Center

Denver, Colorado, United States, 80218

United States, Connecticut

Institute for Neurodegenerative Disorders

New Haven, Connecticut, United States, 06510

United States, District of Columbia

Georgetown University Medical Center

Washington, District of Columbia, United States, 20057

United States, Florida

Brain Matters Research

Delray Beach, Florida, United States, 33445

Direct Helpers Medical Center

Hialeah, Florida, United States, 33012

Berma Research

Hialeah, Florida, United States, 33016

Galiz Research

Hialeah, Florida, United States, 33016

MaxBlue Institute

Hialeah, Florida, United States, 33018

Alzheimer's Research and Treatment Center

Lake Worth, Florida, United States, 33449

Miami Jewish Health Systems

Miami, Florida, United States, 33137

Medical Research Center

Miami, Florida, United States, 33144

Allied Biomedical Research Institute, Inc.

Miami, Florida, United States, 33155

Advance Medical Research Institute

Miami, Florida, United States, 33174

New Horizon Research Center

Miami, Florida, United States, 33175

JDH Medical Group, LLC

Miami, Florida, United States, 33186

Compass Research

Orlando, Florida, United States, 32806

IMIC, Inc.

Palmetto Bay, Florida, United States, 33157

Suncoast Neuroscience Associates

Saint Petersburg, Florida, United States, 33713

Roskamp Institute

Sarasota, Florida, United States, 34243

Infinity Clinical Research, LLC

Sunrise, Florida, United States, 33351

Stedman Clinical Trials

Tampa, Florida, United States, 33613

Olympian Clinical Research

Tampa, Florida, United States, 33614

Compass Research

The Villages, Florida, United States, 32162

Premiere Research Institute at Palm Beach Neurology

West Palm Beach, Florida, United States, 33407

United States, Georgia

The Multiple Sclerosis Center of Atlanta

Atlanta, Georgia, United States, 30327

Atlanta Center of Medical Research

Atlanta, Georgia, United States, 30331

Carman Research

Smyrna, Georgia, United States, 30080

United States, Illinois

University of Chicago Medical Center

Chicago, Illinois, United States, 60637

Alexian Brothers Medical Center

Elk Grove Village, Illinois, United States, 60007

United States, Indiana

Community Clinical Research Center

Anderson, Indiana, United States, 46011

Indiana University School of Medicine

Indianapolis, Indiana, United States, 46202

United States, Massachusetts

ActivMed Practices & Research, Inc

Methuen, Massachusetts, United States, 01844

Boston Center for Memory

Newton, Massachusetts, United States, 02459

Springfield Neurology Associates

Springfield, Massachusetts, United States, 01104

United States, Mississippi

Hattiesburg Clinic

Hattiesburg, Mississippi, United States, 39401

United States, Missouri

Millennium Psychiatric Associates, LLV

Saint Louis, Missouri, United States, 63141

St. Louis Clinical Trials, LC

Saint Louis, Missouri, United States, 63141

United States, New Jersey

Memory Enhancement Center of America, Inc.

Eatontown, New Jersey, United States, 07724

AdvanceMed Research

Lawrenceville, New Jersey, United States, 08648

Alzheimer's Research Company

Manchester, New Jersey, United States, 08759

The Cognitive and Research Center of NJ

Springfield, New Jersey, United States, 07081

Advanced Memory Research Institute of New Jersey

Toms River, New Jersey, United States, 08755

Bio Behavioral Health

Toms River, New Jersey, United States, 08755

Neurology Specialists of Monmouth County

West Long Branch, New Jersey, United States, 07764

United States, New York

Integrative Clinical Trials, LLC

Brooklyn, New York, United States, 11229

SPRI Clinical Trials, LLC.

Brooklyn, New York, United States, 11235

Alzheimer's Disease and Memory Disorders Center

Buffalo, New York, United States, 14203

Empire Neurology, PC

Latham, New York, United States, 12110

Clinilabs, Inc (New York)

New York, New York, United States, 10019

Columbia University Medical Center

New York, New York, United States, 10032

University of Rochester

Rochester, New York, United States, 14620

United States, North Carolina

Alzheimer's Memory Center

Charlotte, North Carolina, United States, 28270

United States, Ohio

Valley Medical Primary Care

Centerville, Ohio, United States, 45459

Christ Hospital

Cincinnati, Ohio, United States, 45219

Ohio State University Medical Center

Columbus, Ohio, United States, 43221

United States, Oregon

The Corvallis Clinic P.C.

Corvallis, Oregon, United States, 97330

United States, Pennsylvania

Lehigh Valley Hospital

Allentown, Pennsylvania, United States, 18103

United States, Rhode Island

Rhode Island Mood & Memory Research Institute

East Providence, Rhode Island, United States, 02914

United States, South Carolina

Roper St. Francis Healthcare

Charleston, South Carolina, United States, 29401

Radiant Research

Greer, South Carolina, United States, 29651

United States, Tennessee

Quillen College of Medicine, East TN State University

Johnson City, Tennessee, United States, 37605

United States, Texas

Senior Adults Specialty Research Inc

Austin, Texas, United States, 78757

Texas Health Physicians Group

Dallas, Texas, United States, 75231

Medical Group of Texas

Fort Worth, Texas, United States, 76104

University of Texas Health Services Center - Houston

Houston, Texas, United States, 77054

United States, Utah

University of Utah School of Medicine

Salt Lake City, Utah, United States, 84108

United States, Vermont

The Memory Clinic

Bennington, Vermont, United States, 05201

Australia, New South Wales

Southern Neurology

Kogarah, New South Wales, Australia, 2217

Australia, Queensland

Griffith University

Gold Coast, Queensland, Australia, 4222

Australia, South Australia

Royal Adelaide Hospital

Adelaide, South Australia, Australia, 5000

Australia, Victoria

Box Hill Hospital

Box Hill, Victoria, Australia, 3128

Delmont Private Hospital

Glen Iris, Victoria, Australia, 3146

Heidelberg Repatriation Hospital

Heidelberg, Victoria, Australia, 3081

The Florey Institute of Neuroscience and Mental Health

Parkville, Victoria, Australia, 3052

Australia, Western Australia

Australian Alzheimer's Research Foundation

Nedlands, Western Australia, Australia, 6009

Australia

Neuro Trials Victoria Pty Ltd

Noble Park, Australia, 3174

Belgium

Jessa Ziekenhuis

Hasselt, Limburg, Belgium, 3500

Hopital Universitaire Brugmann Brussel

Brussels, Belgium, 1020

Cliniques Universitaires Saint-Luc

Brussels, Belgium, 1200

Hospital Universitaire Erasme Brussel

Brussel, Belgium, 1070

Universitair Ziekenhuis Antwerpen

Edegem, Belgium, 2650

Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg

Leuven, Belgium, 3000

Heilig Hartziekenhuis

Roeselare, Belgium, 8800

Canada, British Columbia

The Medical Arts Health Research Group

Kamloops, British Columbia, Canada, V2C 1K7

Okanagan Clinical Trials

Kelowna, British Columbia, Canada, V1Y 1Z9

University of British Columbia

Vancouver, British Columbia, Canada, V6T 2B5

Royal Jubilee Hospital

Victoria, British Columbia, Canada, V8R 158

Canada, Nova Scotia

True North Clinical Research Halifax, LLC

Halifax, Nova Scotia, Canada, B3S1M7

Canada, Ontario

Bruyere Continuing Care

Ottawa, Ontario, Canada, K1N 5C8

Kawartha Regional Memory Clinic

Peterborough, Ontario, Canada, K9H2P4

Toronto Memory Program

Toronto, Ontario, Canada, M3B2S7

Toronto Western Hospital

Toronto, Ontario, Canada, M5T2S8

Canada, Qubec

CSSS-Institut Universitaire Gériatric de Sherbrooke

Sherbrooke, Qubec, Canada, J1J3H5

Canada, Quebec

Clinique de la Memoire de l'Outaouais

Gatineau, Quebec, Canada, J8T 8J1

NeuroSearch Developements

Greenfield Park, Quebec, Canada, J4V 2J2

Hopital Maisonneure-Rosemount

Montreal, Quebec, Canada, H1T 2M4

Hopital de L'Enfant Jesus

Quebec City, Quebec, Canada, G1J 1Z4

Q&T Research Sherbrooke Inc

Sherbrooke, Quebec, Canada, J1J 2G2

France

CHU de Toulouse Hopital Purpan

Toulouse, Cedex 9, France, 31059

Hopital Neuro Pierre Wertheimer

Bron Cedex, France, 69677

CHU Dijonon

Dijon Cedex, France, 21033

CHRU Lille - Hopital Roger Salengro

Lille Cedex, France, 59037

CHU Hopital de la Timone

Marseille Cedex 05, France, 13385

Chu de Nantes Hopital Laennec

Nantes, France, 44093

Hopital Broca

Paris, France, 75013

Hopital de la Pitie Salpetriere

Paris, France, 75013

Hopital Lariboisière

Paris, France, 75475

CHU de Toulouse

Toulouse, France, 31052

Hopital des Charpennes

Villeurbanne, France, 69100

Germany

Universitätsklinikum Tübingen

Tübingen, Baden-Württemberg, Germany, 72076

Universitätsklinikum Ulm

Ulm, Baden-Württemberg, Germany, 89081

Studien und Gedächtniszentrum München

München, Bayern, Germany, 80331

Klinikum Rechts der Isar der TU München

München, Bayern, Germany, 81675

Institut fur Psychogerontologie

Nürnberg, Bayern, Germany, 90402

Neurozentrum Prien

Prien am Chiemsee, Bayern, Germany, 83209

Institut für Neuropsychiatrie INP3

Wenzenbach, Bayern, Germany, 93173

Studienzentrum Nord-West

Westerstede, Niedersachsen, Germany, 26655

Praxis Dr. Lauter

Bochum, Nordrhein-Westfalen, Germany, 44787

St Josef-Hospital Bochum

Bochum, Nordrhein-Westfalen, Germany, 44791

Universitätsklinikum Bonn

Bonn, Nordrhein-Westfalen, Germany, 53105

Gemeinschaftspraxis für Neurologie Prof. Gereon Nelles

Köln, Nordrhein-Westfalen, Germany, 50935

Universitätsklinikum Köln

Köln, Nordrhein-Westfalen, Germany, 50937

Neurologische Praxis Siegen

Siegen, Nordrhein-Westfalen, Germany, 57076

Universitätsklinikum des Saarlandes

Homburg, Saarland, Germany, 66421

Martin-Luther-Universität Halle-Wittenberg

Halle (Saale), Sachsen-Anhalt, Germany, 06097

Universitätsklinikum Otto-von-Guericke-Universität

Magdeburg, Sachsen-Anhalt, Germany, 39120

Pharmakologisches Studienzentrum Chemnitz

Mittweida, Sachsen, Germany, 09648

Arztpraxis Dr. Christian Oehlwein

Gera, Thüringen, Germany, 07551

Gemeinschaftspraxis Dr. R. Ehret & Dr. W. von Pannwitz

Berlin, Germany, 12163

Charité Universitätsmedizin Berlin

Berlin, Germany, 12203

Charité Universitätsmedizin Berlin

Berlin, Germany, 13353

Hungary

PTE KK Pszichiatriai es Pszichoterapias Klinika

Pecs, Baranya, Hungary, 7623

Semmelweis Medical University

Budapest, Hungary, 1083

Del-pesti Centrumkorház - Orszagos Hematologiai és Infektologiai Intezet

Budapest, Hungary, 1097

Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz

Debrecen, Hungary, 4031

Debreceni Egyetem Klinikai Kozpont

Debrecen, Hungary, 4032

Univerisity of Szeged

Szeged, Hungary, 6725

Italy

Ospedale Degli Infermi ASR USSL 12

Ponderano, Biella, Italy, 13875

Azienda Ospedaliera San Gerardo

Monza, Milano, Italy, 20900

Fondazione San Raffaele Giglio di Cefalu

Cefalu, Palermo, Italy, 90015

Universita Di Pisa

Pisa, PI, Italy, 56126

Università Politecnica delle Marche Torrette

Ancona, Italy, 60126

IRCCS San Giovanni di Dio Fatebenefratelli

Brescia, Italy, 25125

Fondazione Universitaria degli Studi G D'Annunzio

Chieti, Italy, 66100

Ente Ospedaliero Ospedali Galliera

Genova, Italy, 16132

Fondazione IRCCS Ca'Granda Ospedale Maggiore Policinico

Milano, Italy, 20122

Nuovo Ospedale Civile Sant'Agostino Estense

Modena, Italy, 41010

Policlinico Univ. Agostino Gemelli

Roma, Italy, 00168

Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza

Roma, Italy, 00185

Ospedale San Giovanni Calibita Fatebenefratelli

Roma, Italy, 00186

Policlinico Ospedale S. Andrea

Roma, Italy, 00189

Azienda Ospedaliera Citta della Salute della Scienza Torino

Torino, Italy, 10126

Japan

National Institute for Longevity Sciences NCGG

Obu, Aichi, Japan, 474-0038

National Chiba-East-Hospital

Chuo-ku, Chiba, Japan, 260-8712

National Hospital Organization Asahikawa Medical Center

Asahikawa, Hokkaido, Japan, 070-8644

Tsukuba University Hospital

Tsukuba, Ibaraki, Japan, 305-8576

Iwate Medical University Hospital

Morioka, Iwate, Japan, 020-8505

Shonan Kamakura General Hospital

Kamakura, Kanagawa, Japan, 247-8533

Nihon Kokan Hospital

Kawasaki, Kanagawa, Japan, 210-0852

Yokohama City University Hospital

Yokohama, Kanagawa, Japan, 236-0004

Kyoto Prefectural University of Medicine

Kyoto-shi, Kyoto, Japan, 602-8566

Rakuwakai Otowarehabilitation Hospital

Kyoto-shi, Kyoto, Japan, 607-8113

Ina Central Hospital

Ina, Nagano, Japan, 396-8555

Matsumoto Medical Center

Matsumoto, Nagano, Japan, 399-0021

Katayama Medical Clinic

Kurashiki, Okayama, Japan, 701-0192

Shiroma Clinic

Urasoe, Okinawa, Japan, 901-2102

Koshokai aino hospital

Ibaraki, Osaka, Japan, 567-0011

Sakaguchi Clinic

Sakai, Osaka, Japan, 593-8301

National Sanatorium Toneyama Hospital

Toyonaka, Osaka, Japan, 560-8552

Saitama Medical University Hospital

Iruma-Gun, Saitama, Japan, 350-0495

Nippon Medical School Hospital

Bunkyo-Ku, Tokyo, Japan, 113-8603

The University of Tokyo Hospital

Bunkyo-ku, Tokyo, Japan, 113-8655

Nozomi Memory Clinic

Mitaka-shi, Tokyo, Japan, 181-0013

Sangenjaya Nakamura Mental Clinic

Setagaya, Tokyo, Japan, 154-0004

Kanauchi Medical Clinic

Shinjuku-ku, Tokyo, Japan, 160-0023

Tokyo Women's Medical University Hospital

Shinjuku-ku, Tokyo, Japan, 162-8666

Memory Clinic Ochanomizu

Tsukuba, Tokyo, Japan, 305 8576

National Sanatorium Hokuriku Hospital

Nanto, Toyama, Japan, 939-1893

Fukuoka University Hospital

Fukuoka, Japan, 814-0180

Kyoto University Hospital

Kyoto, Japan, 606-8507

Kyoto Minami Hospital

Kyoto, Japan, 610-0113

Utano Hospital

Kyoto, Japan, 616-8255

For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Osaka, Japan, 545-8586

Korea, Republic of

Dong-A University Medical Center

Seogu, Busan, Korea, Republic of, 49201

Seoul National University Bundang Hospital

Seongnam-si, Geonggi-do, Korea, Republic of, 13620

The Catholic University of Korea-Bucheon St. Mary's Hospital

Bucheon-si, Gyeonggi-do, Korea, Republic of, 14647

Hanyang University Guri Hospital

Guri-si, Gyeonggido, Korea, Republic of, 11923

Gachon University Gil Medical Center

Namdong, Incheon, Korea, Republic of, 21565

Inha University Hospital

Incheon, Korea, Republic of, 22332

Asan Medical Center

Seoul, Korea, Republic of, 05505

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Seoul St. Mary's Hospital

Seoul, Korea, Republic of, 06591

Poland

NZOZ Wroclawskie Centrum Alzheimerowskie

Wroclaw, Dolnoslaskie, Poland, 53 139

Medycyna Milorzab

Lodz, Lódzkie, Poland, 92216

Podlaskie Centrum Psychogeriatrii

Białystok, Podlaskie, Poland, 15-732

NZOZ Dom Sue Ryder - Pallmed Sp. z o.o.

Bydgoszcz, Poland, 85-796

NZOZ Wielospecjalistyczna Poradnia Lekarska

Katowice, Poland, 40-123

Specjalistyczna Praktyka Lekarska prof. Grzegorz Opala

Katowice, Poland, 40-588

Centrum Zdrowia Psychicznego

Kielce, Poland, 25411

Centrum Neurologii Klinicznej

Krakow, Poland, 31-505

NZOZ Neuromed M. I M. Nastaj sp. P.

Lublin, Poland, 20-064

Instytut Medycyny Wsi

Lublin, Poland, 20-090

NEURO-CARE Sp. z o.o. Sp. Komandytowa

Siemianowice Śląskie, Poland, 41-100

Centrum Medyczne

Warszawa, Poland, 01-697

Centralny Szpital Kliniczny MSW

Warszawa, Poland, 02-507

Puerto Rico

Santa Cruz Behavioral PSC

Bayamon, Puerto Rico, 00961

Ivonne Z. Jimenez-Velazquez, MD

Carolina, Puerto Rico, 00984

Instituto de Neurologia Dra. Ivonne Fraga

San Juan, Puerto Rico, 00918

Michel A. Woodbury-Farina, MD.

San Juan, Puerto Rico, 00918

Romania

SC Med Life SA

Bucuresti, Romania, 010719

SC Centrul Medical Sana SRL

Bucuresti, Romania, 011025

Policlinica CCBR S.R.L.

Bucuresti, Romania, 30463

SC Med Life SA

Timisoara, Romania, 300166

Spain

Hospital General Universitario de Elche

Elche, Alicante, Spain, 03203

Hospital General de Catalunya

Sant Cugat del Valles, Barcelona, Spain, 08190

Hospital Virgen Del Puerto

Plasencia, Caceres, Spain, 10600

Hospital Universitario De Getafe

Madrid, Getafe, Spain, 28905

Hospital Puerta De Hierro

Majadahonda, Madrid, Spain, 28222

Centro de Atencion Especializada (CAE) OROITU

Getxo, Vizcaya, Spain, 48993

Hospital del Mar

Barcelona, Spain, 08003

Hospital Santa Creu I Sant Pau

Barcelona, Spain, 08025

Fundacion ACE-Institut Catala de Neurociences Aplicades

Barcelona, Spain, 08028

Hospital Clinic de Barcelona

Barcelona, Spain, 08036

Hospital Universitari de Bellvitge

Barcelona, Spain, 08907

Hospital Reina Sofia

Cordoba, Spain, 14004

Hospital De La Princesa

Madrid, Spain, 28006

Hospital Universitario Ramon y Cajal

Madrid, Spain, 28034

Hospital Son Espases

Palma de Mallorca, Spain, 07010

Hospital Univ Sant Joan de Reus, S.A.

Reus, Spain, 43204

Fundacion CITA Alzheimer

San Sebastian, Spain, 20009

Hospital Doctor Peset

Valencia, Spain, 46017

Hospital Universitario La Fe de Valencia

Valencia, Spain, 46026

United Kingdom

Plymouth Hospitals NHS Trust

Plymouth, Devon, United Kingdom, PL6 8BX

Cognitive Treatment & Research Unit

Crowborough, East Sussex, United Kingdom, TN6 1HB

Southern Health NHS

Southampton, Hampshire, United Kingdom, SO30 3JB

MAC UK Neuroscience Ltd

Blackpool, Lancs, United Kingdom, FY20JH

MAC Clinical Research

Stourton, Leeds, United Kingdom, LS10 1DU

MAC Clinical Research

Cannock, Staffordshire, United Kingdom, WS11 0BN

West London Mental Health NHS Trust

Brentford, United Kingdom, TW8 8DS

Glasgow Memory Clinic

Glasgow, United Kingdom, G20 0XA

Hammersmith Hospital

London, United Kingdom, W12 0NN

Guildford Nuffield Hospital

London, United Kingdom, W1G 9JF

Re-Cognition Health Ltd

London, United Kingdom, W1G 9RU

MAC Clinical Research

Manchester, United Kingdom, M13 9NQ

Sponsors and Collaborators

AstraZeneca

Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon- Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST); Eli Lilly and Company

  Study Documents (Full-Text)

Documents provided by AstraZeneca:

Study Protocol  [PDF] July 17, 2017

Statistical Analysis Plan  [PDF] August 17, 2018

More Information

Additional Information:

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

CSP 

SAP 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02245737
• Other Study ID Numbers: 16023; I8D-MC-AZES ( Other Identifier: Eli Lilly and Company ); 2014-002601-38 ( EudraCT Number ); D5010C00009 ( Other Identifier: AstraZeneca )
• First Posted: September 22, 2014
• Results First Posted: August 6, 2019
• Last Update Posted: December 3, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)
• 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.
• Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• URL: https://www.clinicalstudydatarequest.com/

Keywords provided by AstraZeneca:

Alzheimer's disease; Dementia; Brain Diseases; Neurogenerative Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Delirium, Dementia, Amnestic, Cognitive Disorders; Tauopathies

Additional relevant MeSH terms:

Alzheimer Disease; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders