An Efficacy and Safety Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease
- Registration Number
- NCT02245737
- Lead Sponsor
- AstraZeneca
- 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.
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 2218
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Placebo given orally once daily for 104 weeks. Lanabecestat 20 milligrams (mg) Lanabecestat Lanabecestat 20 mg given orally once daily for 104 weeks. Lanabecestat 50 mg Lanabecestat Lanabecestat 50 mg given orally once daily for 104 weeks.
- Primary Outcome Measures
Name Time Method Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) 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
Name Time Method Change From Baseline on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL) 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.
Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage 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).
Change From Baseline in Neuropsychiatric Inventory (NPI) Score 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.
Change From Baseline on the Mini-Mental State Examination (MMSE) 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.
Pharmacodynamics (PD): Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42 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.
PD: Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40 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.
Change From Baseline in CSF Total Tau 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.
Change From Baseline in CSF Phosphorylated Tau 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.
Change From Baseline on the Functional Activities Questionnaire (FAQ) Score 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.
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score 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.
Change From Baseline on the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score 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.
Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan 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.
Change From Baseline in Tau PET ((Flortaucipir F18) 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.
Change From Baseline in Brain Metabolism Using Fluorodeoxyglucose (FDG) 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.
Change From Baseline in Whole Brain Volume 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.
Pharmacokinetics (PK): Plasma Concentration of Lanabecestat Week 4, post dose prior to departure from the clinic
Trial Locations
- Locations (249)
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Q&T Research Sherbrooke Inc
🇨🇦Sherbrooke, Quebec, Canada
Banner Sun Health Research Institute
🇺🇸Sun City, Arizona, United States
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Advanced Memory Research Institute of New Jersey
🇺🇸Toms River, New Jersey, United States
Tsukuba University Hospital
🇯🇵Tsukuba, Ibaraki, Japan
Iwate Medical University Hospital
🇯🇵Morioka, Iwate, Japan
Universitätsklinikum Tübingen
🇩🇪Tübingen, Baden-Württemberg, Germany
Semmelweis Medical University
🇭🇺Budapest, Hungary
National Sanatorium Toneyama Hospital
🇯🇵Toyonaka, Osaka, Japan
Fukuoka University Hospital
🇯🇵Fukuoka, Japan
Nozomi Memory Clinic
🇯🇵Mitaka-shi, Tokyo, Japan
NEURO-CARE Sp. z o.o. Sp. Komandytowa
🇵🇱Siemianowice Śląskie, Poland
Centrum Zdrowia Psychicznego
🇵🇱Kielce, Poland
Santa Cruz Behavioral PSC
🇵🇷Bayamon, Puerto Rico
SC Centrul Medical Sana SRL
🇷🇴Bucuresti, Romania
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Policlinica CCBR S.R.L.
🇷🇴Bucuresti, Romania
Cognitive Treatment & Research Unit
🇬🇧Crowborough, East Sussex, United Kingdom
Alliance Research Centers
🇺🇸Laguna Hills, California, United States
Senior Clinical Trials, Inc.
🇺🇸Laguna Hills, California, United States
Positron Research International
🇺🇸Fremont, California, United States
Brain Matters Research
🇺🇸Delray Beach, Florida, United States
Direct Helpers Medical Center
🇺🇸Hialeah, Florida, United States
MaxBlue Institute
🇺🇸Hialeah, Florida, United States
Berma Research
🇺🇸Hialeah, Florida, United States
Galiz Research
🇺🇸Hialeah, Florida, United States
Alzheimer's Research and Treatment Center
🇺🇸Lake Worth, Florida, United States
Allied Biomedical Research Institute, Inc.
🇺🇸Miami, Florida, United States
Compass Research
🇺🇸The Villages, Florida, United States
Roskamp Institute
🇺🇸Sarasota, Florida, United States
Infinity Clinical Research, LLC
🇺🇸Sunrise, Florida, United States
Suncoast Neuroscience Associates
🇺🇸Saint Petersburg, Florida, United States
Premiere Research Institute at Palm Beach Neurology
🇺🇸West Palm Beach, Florida, United States
The Multiple Sclerosis Center of Atlanta
🇺🇸Atlanta, Georgia, United States
Atlanta Center of Medical Research
🇺🇸Atlanta, Georgia, United States
Carman Research
🇺🇸Smyrna, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Alexian Brothers Medical Center
🇺🇸Elk Grove Village, Illinois, United States
Community Clinical Research Center
🇺🇸Anderson, Indiana, United States
ActivMed Practices & Research, Inc
🇺🇸Methuen, Massachusetts, United States
The Cognitive and Research Center of NJ
🇺🇸Springfield, New Jersey, United States
Bio Behavioral Health
🇺🇸Toms River, New Jersey, United States
Integrative Clinical Trials, LLC
🇺🇸Brooklyn, New York, United States
Neurology Specialists of Monmouth County
🇺🇸West Long Branch, New Jersey, United States
Box Hill Hospital
🇦🇺Box Hill, Victoria, Australia
Hopital de L'Enfant Jesus
🇨🇦Quebec City, Quebec, Canada
Clinique de la Memoire de l'Outaouais
🇨🇦Gatineau, Quebec, Canada
CHU Hopital de la Timone
🇫🇷Marseille Cedex 05, France
Chu de Nantes Hopital Laennec
🇫🇷Nantes, France
Hopital Broca
🇫🇷Paris, France
CHU de Toulouse
🇫🇷Toulouse, France
Hopital de la Pitie Salpetriere
🇫🇷Paris, France
Hopital des Charpennes
🇫🇷Villeurbanne, France
Hopital Lariboisière
🇫🇷Paris, France
Universitätsklinikum Ulm
🇩🇪Ulm, Baden-Württemberg, Germany
Studien und Gedächtniszentrum München
🇩🇪München, Bayern, Germany
Klinikum Rechts der Isar der TU München
🇩🇪München, Bayern, Germany
Institut für Neuropsychiatrie INP3
🇩🇪Wenzenbach, Bayern, Germany
Neurozentrum Prien
🇩🇪Prien am Chiemsee, Bayern, Germany
Institut fur Psychogerontologie
🇩🇪Nürnberg, Bayern, Germany
Studienzentrum Nord-West
🇩🇪Westerstede, Niedersachsen, Germany
St Josef-Hospital Bochum
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Praxis Dr. Lauter
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Neurologische Praxis Siegen
🇩🇪Siegen, Nordrhein-Westfalen, Germany
Gemeinschaftspraxis für Neurologie Prof. Gereon Nelles
🇩🇪Köln, Nordrhein-Westfalen, Germany
Universitätsklinikum Bonn
🇩🇪Bonn, Nordrhein-Westfalen, Germany
Universitätsklinikum Köln
🇩🇪Köln, Nordrhein-Westfalen, Germany
Universitätsklinikum Otto-von-Guericke-Universität
🇩🇪Magdeburg, Sachsen-Anhalt, Germany
Martin-Luther-Universität Halle-Wittenberg
🇩🇪Halle (Saale), Sachsen-Anhalt, Germany
Pharmakologisches Studienzentrum Chemnitz
🇩🇪Mittweida, Sachsen, Germany
Gemeinschaftspraxis Dr. R. Ehret & Dr. W. von Pannwitz
🇩🇪Berlin, Germany
Arztpraxis Dr. Christian Oehlwein
🇩🇪Gera, Thüringen, Germany
PTE KK Pszichiatriai es Pszichoterapias Klinika
🇭🇺Pecs, Baranya, Hungary
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
Del-pesti Centrumkorház - Orszagos Hematologiai és Infektologiai Intezet
🇭🇺Budapest, Hungary
Univerisity of Szeged
🇭🇺Szeged, Hungary
Debreceni Egyetem Kenezy Gyula Egyetemi Korhaz
🇭🇺Debrecen, Hungary
Fondazione Universitaria degli Studi G D'Annunzio
🇮🇹Chieti, Italy
National Institute for Longevity Sciences NCGG
🇯🇵Obu, Aichi, Japan
Shonan Kamakura General Hospital
🇯🇵Kamakura, Kanagawa, Japan
Nihon Kokan Hospital
🇯🇵Kawasaki, Kanagawa, Japan
Kyoto Prefectural University of Medicine
🇯🇵Kyoto-shi, Kyoto, Japan
Koshokai aino hospital
🇯🇵Ibaraki, Osaka, Japan
Saitama Medical University Hospital
🇯🇵Iruma-Gun, Saitama, Japan
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
The University of Tokyo Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
Nippon Medical School Hospital
🇯🇵Bunkyo-Ku, Tokyo, Japan
Sangenjaya Nakamura Mental Clinic
🇯🇵Setagaya, Tokyo, Japan
Kanauchi Medical Clinic
🇯🇵Shinjuku-ku, Tokyo, Japan
Memory Clinic Ochanomizu
🇯🇵Tsukuba, Tokyo, Japan
National Sanatorium Hokuriku Hospital
🇯🇵Nanto, Toyama, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Kyoto Minami Hospital
🇯🇵Kyoto, Japan
Utano Hospital
🇯🇵Kyoto, Japan
Dong-A University Medical Center
🇰🇷Seogu, Busan, Korea, Republic of
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
The Catholic University of Korea-Bucheon St. Mary's Hospital
🇰🇷Bucheon-si, Gyeonggi-do, Korea, Republic of
Hanyang University Guri Hospital
🇰🇷Guri-si, Gyeonggido, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Geonggi-do, Korea, Republic of
Inha University Hospital
🇰🇷Incheon, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Namdong, Incheon, Korea, Republic of
Centrum Neurologii Klinicznej
🇵🇱Krakow, Poland
NZOZ Wielospecjalistyczna Poradnia Lekarska
🇵🇱Katowice, Poland
Centrum Medyczne
🇵🇱Warszawa, Poland
Michel A. Woodbury-Farina, MD.
🇵🇷San Juan, Puerto Rico
Centro de Atencion Especializada (CAE) OROITU
🇪🇸Getxo, Vizcaya, Spain
Hospital Puerta De Hierro
🇪🇸Majadahonda, Madrid, Spain
Hospital Universitario De Getafe
🇪🇸Madrid, Getafe, Spain
Fundacion ACE-Institut Catala de Neurociences Aplicades
🇪🇸Barcelona, Spain
Hospital Son Espases
🇪🇸Palma de Mallorca, Spain
Fundacion CITA Alzheimer
🇪🇸San Sebastian, Spain
Hospital Doctor Peset
🇪🇸Valencia, Spain
West London Mental Health NHS Trust
🇬🇧Brentford, United Kingdom
Hammersmith Hospital
🇬🇧London, United Kingdom
Re-Cognition Health Ltd
🇬🇧London, United Kingdom
Guildford Nuffield Hospital
🇬🇧London, United Kingdom
Universitätsklinikum des Saarlandes
🇩🇪Homburg, Saarland, Germany
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
St Josephs Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
Pacific Research Network Inc
🇺🇸San Diego, California, United States
San Francisco Clinical Research Center
🇺🇸San Francisco, California, United States
Medical Research Center
🇺🇸Miami, Florida, United States
New Horizon Research Center
🇺🇸Miami, Florida, United States
JDH Medical Group, LLC
🇺🇸Miami, Florida, United States
Mile High Research Center
🇺🇸Denver, Colorado, United States
Miami Jewish Health Systems
🇺🇸Miami, Florida, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Advance Medical Research Institute
🇺🇸Miami, Florida, United States
University of Utah School of Medicine
🇺🇸Salt Lake City, Utah, United States
Azienda Ospedaliera San Gerardo
🇮🇹Monza, Milano, Italy
IRCCS San Giovanni di Dio Fatebenefratelli
🇮🇹Brescia, Italy
Ente Ospedaliero Ospedali Galliera
🇮🇹Genova, Italy
Nuovo Ospedale Civile Sant'Agostino Estense
🇮🇹Modena, Italy
Azienda Ospedaliera Citta della Salute della Scienza Torino
🇮🇹Torino, Italy
Ospedale San Giovanni Calibita Fatebenefratelli
🇮🇹Roma, Italy
Policlinico Univ. Agostino Gemelli
🇮🇹Roma, Italy
Dip.to Med. Sperimentale -Polic.Umberto I -Univ. La Sapienza
🇮🇹Roma, Italy
Collaborative Neuroscience Network - CNS
🇺🇸Long Beach, California, United States
St. Louis Clinical Trials, LC
🇺🇸Saint Louis, Missouri, United States
Boston Center for Memory
🇺🇸Newton, Massachusetts, United States
Millennium Psychiatric Associates, LLV
🇺🇸Saint Louis, Missouri, United States
Alzheimer's Research Company
🇺🇸Manchester, New Jersey, United States
Hattiesburg Clinic
🇺🇸Hattiesburg, Mississippi, United States
Memory Enhancement Center of America, Inc.
🇺🇸Eatontown, New Jersey, United States
AdvanceMed Research
🇺🇸Lawrenceville, New Jersey, United States
SPRI Clinical Trials, LLC.
🇺🇸Brooklyn, New York, United States
Alzheimer's Disease and Memory Disorders Center
🇺🇸Buffalo, New York, United States
Clinilabs, Inc (New York)
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Christ Hospital
🇺🇸Cincinnati, Ohio, United States
Empire Neurology, PC
🇺🇸Latham, New York, United States
Alzheimer's Memory Center
🇺🇸Charlotte, North Carolina, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Valley Medical Primary Care
🇺🇸Centerville, Ohio, United States
The Corvallis Clinic P.C.
🇺🇸Corvallis, Oregon, United States
Texas Health Physicians Group
🇺🇸Dallas, Texas, United States
University of Texas Health Services Center - Houston
🇺🇸Houston, Texas, United States
Quillen College of Medicine, East TN State University
🇺🇸Johnson City, Tennessee, United States
The Memory Clinic
🇺🇸Bennington, Vermont, United States
Griffith University
🇦🇺Gold Coast, Queensland, Australia
Hopital Universitaire Brugmann Brussel
🇧🇪Brussels, Belgium
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Hospital Universitaire Erasme Brussel
🇧🇪Brussel, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Bruyere Continuing Care
🇨🇦Ottawa, Ontario, Canada
Royal Jubilee Hospital
🇨🇦Victoria, British Columbia, Canada
The Medical Arts Health Research Group
🇨🇦Kamloops, British Columbia, Canada
Heidelberg Repatriation Hospital
🇦🇺Heidelberg, Victoria, Australia
Okanagan Clinical Trials
🇨🇦Kelowna, British Columbia, Canada
Neuro Trials Victoria Pty Ltd
🇦🇺Noble Park, Australia
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Heilig Hartziekenhuis
🇧🇪Roeselare, Belgium
Hopital Maisonneure-Rosemount
🇨🇦Montreal, Quebec, Canada
CHU de Toulouse Hopital Purpan
🇫🇷Toulouse, Cedex 9, France
Hopital Neuro Pierre Wertheimer
🇫🇷Bron Cedex, France
Delmont Private Hospital
🇦🇺Glen Iris, Victoria, Australia
Toronto Memory Program
🇨🇦Toronto, Ontario, Canada
Toronto Western Hospital
🇨🇦Toronto, Ontario, Canada
University of British Columbia
🇨🇦Vancouver, British Columbia, Canada
The Florey Institute of Neuroscience and Mental Health
🇦🇺Parkville, Victoria, Australia
Australian Alzheimer's Research Foundation
🇦🇺Nedlands, Western Australia, Australia
Kawartha Regional Memory Clinic
🇨🇦Peterborough, Ontario, Canada
Jessa Ziekenhuis
🇧🇪Hasselt, Limburg, Belgium
True North Clinical Research Halifax, LLC
🇨🇦Halifax, Nova Scotia, Canada
NeuroSearch Developements
🇨🇦Greenfield Park, Quebec, Canada
CHRU Lille - Hopital Roger Salengro
🇫🇷Lille Cedex, France
CHU Dijonon
🇫🇷Dijon Cedex, France
Debreceni Egyetem Klinikai Kozpont
🇭🇺Debrecen, Hungary
Ospedale Degli Infermi ASR USSL 12
🇮🇹Ponderano, Biella, Italy
Fondazione San Raffaele Giglio di Cefalu
🇮🇹Cefalu, Palermo, Italy
Universita Di Pisa
🇮🇹Pisa, PI, Italy
Università Politecnica delle Marche Torrette
🇮🇹Ancona, Italy
Fondazione IRCCS Ca'Granda Ospedale Maggiore Policinico
🇮🇹Milano, Italy
Policlinico Ospedale S. Andrea
🇮🇹Roma, Italy
National Chiba-East-Hospital
🇯🇵Chuo-ku, Chiba, Japan
National Hospital Organization Asahikawa Medical Center
🇯🇵Asahikawa, Hokkaido, Japan
Yokohama City University Hospital
🇯🇵Yokohama, Kanagawa, Japan
Rakuwakai Otowarehabilitation Hospital
🇯🇵Kyoto-shi, Kyoto, Japan
Ina Central Hospital
🇯🇵Ina, Nagano, Japan
Matsumoto Medical Center
🇯🇵Matsumoto, Nagano, Japan
Katayama Medical Clinic
🇯🇵Kurashiki, Okayama, Japan
Shiroma Clinic
🇯🇵Urasoe, Okinawa, Japan
Sakaguchi Clinic
🇯🇵Sakai, Osaka, Japan
NZOZ Wroclawskie Centrum Alzheimerowskie
🇵🇱Wroclaw, Dolnoslaskie, Poland
NZOZ Neuromed M. I M. Nastaj sp. P.
🇵🇱Lublin, Poland
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Medycyna Milorzab
🇵🇱Lodz, Lódzkie, Poland
Podlaskie Centrum Psychogeriatrii
🇵🇱Białystok, Podlaskie, Poland
NZOZ Dom Sue Ryder - Pallmed Sp. z o.o.
🇵🇱Bydgoszcz, Poland
Hospital del Mar
🇪🇸Barcelona, Spain
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
SC Med Life SA
🇷🇴Timisoara, Romania
Hospital De La Princesa
🇪🇸Madrid, Spain
Hospital General de Catalunya
🇪🇸Sant Cugat del Valles, Barcelona, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Specjalistyczna Praktyka Lekarska prof. Grzegorz Opala
🇵🇱Katowice, Poland
Instytut Medycyny Wsi
🇵🇱Lublin, Poland
Centralny Szpital Kliniczny MSW
🇵🇱Warszawa, Poland
Ivonne Z. Jimenez-Velazquez, MD
🇵🇷Carolina, Puerto Rico
Instituto de Neurologia Dra. Ivonne Fraga
🇵🇷San Juan, Puerto Rico
Hospital Reina Sofia
🇪🇸Cordoba, Spain
Hospital Univ Sant Joan de Reus, S.A.
🇪🇸Reus, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
MAC Clinical Research
🇬🇧Manchester, United Kingdom
Plymouth Hospitals NHS Trust
🇬🇧Plymouth, Devon, United Kingdom
MAC UK Neuroscience Ltd
🇬🇧Blackpool, Lancs, United Kingdom
Hospital Virgen Del Puerto
🇪🇸Plasencia, Caceres, Spain
Hospital Universitari de Bellvitge
🇪🇸Barcelona, Spain
Southern Health NHS
🇬🇧Southampton, Hampshire, United Kingdom
Glasgow Memory Clinic
🇬🇧Glasgow, United Kingdom
Hospital Universitario La Fe de Valencia
🇪🇸Valencia, Spain
Springfield Neurology Associates
🇺🇸Springfield, Massachusetts, United States
IMIC, Inc.
🇺🇸Palmetto Bay, Florida, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
Medical Group of Texas
🇺🇸Fort Worth, Texas, United States
University of Rochester
🇺🇸Rochester, New York, United States
Territory Neurology & Research Institute
🇺🇸Tucson, Arizona, United States
Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
CSSS-Institut Universitaire Gériatric de Sherbrooke
🇨🇦Sherbrooke, Qubec, Canada
Southern Neurology
🇦🇺Kogarah, New South Wales, Australia
Institute for Neurodegenerative Disorders
🇺🇸New Haven, Connecticut, United States
Stedman Clinical Trials
🇺🇸Tampa, Florida, United States
Olympian Clinical Research
🇺🇸Tampa, Florida, United States
Roper St. Francis Healthcare
🇺🇸Charleston, South Carolina, United States
Senior Adults Specialty Research Inc
🇺🇸Austin, Texas, United States
Radiant Research
🇺🇸Greer, South Carolina, United States