MedPath

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

Phase 3
Terminated
Conditions
Alzheimer's Disease
Interventions
Drug: Placebo
Registration Number
NCT02783573
Lead Sponsor
AstraZeneca
Brief Summary

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

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
1722
Inclusion Criteria
  • Participant must meet the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (NIA-AA) criteria for probable AD dementia.
  • MMSE score of 20 to 26 inclusive at screening visit.
  • For a diagnosis of mild AD dementia, participant must have a CDR global score of 0.5 or 1, with the memory box score ≥0.5 at screening.
  • Evidence of amyloid pathology.
  • The participant must have a reliable study partner with whom he/she cohabits or has regular contact.
Exclusion Criteria
  • Significant and/or current neurological disease affecting the central nervous system, other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, repetitive head trauma, serious infection of the brain, Parkinson's disease, epilepsy, or cervicocranial vascular disease.
  • Participants with any current primary psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessment, or affect the participant's ability to complete the study. Participants with history of schizophrenia or other chronic psychosis are excluded.
  • Within 1 year before the screening visit or between screening and randomization, any of the following: myocardial infarction; moderate or severe congestive heart failure, New York Heart Association class III or IV; hospitalization for, or symptoms of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (such as, significant valvular disease, hypertrophic cardiomyopathy); or hospitalization for arrhythmia.
  • Congenital QT prolongation.
  • Intermittent second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia.
  • A corrected QT (QTcF) interval measurement >470 milliseconds (men and women) at screening (as determined at the investigational site).
  • History of malignant cancer within the last 5 years.
  • History of vitiligo and/or current evidence of post-inflammatory hypopigmentation.
  • Calculated creatinine clearance <30 milliliters per minute (Cockcroft-Gault formula; Cockcroft and Gault 1976) at screening.
  • Currently enrolled in any other clinical trial involving an investigational product or any other type of medical research judged not to be scientifically or medically compatible with this study.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo/ Lanabecestat 50 mgLanabecestatPlacebo given orally once daily for 78 weeks and then 50 mg of lanabecestat given orally once daily until week 156.
Placebo/ Lanabecestat 20 mgLanabecestatPlacebo given orally once daily for 78 weeks and then 20 mg of lanabecestat given orally once daily until week 156.
Placebo/ Lanabecestat 20 mgPlaceboPlacebo given orally once daily for 78 weeks and then 20 mg of lanabecestat given orally once daily until week 156.
Placebo/ Lanabecestat 50 mgPlaceboPlacebo given orally once daily for 78 weeks and then 50 mg of lanabecestat given orally once daily until week 156.
Lanabecestat 50 mgLanabecestatParticipants received Lanabecestat 50 mg film-coated tablets orally once daily until week 156.
Lanabecestat 20 milligrams (mg)LanabecestatParticipants received Lanabecestat 20 mg film-coated tablets orally once daily until week 156.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog13) ScoreBaseline, Week 78

ADAS-Cog13 (13-item version of ADAS Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment-by-visit interaction, acetylcholinesterase Inhibitor (AChEI) use at baseline, pooled site, and covariates for baseline ADAS-Cog13 total score, age at baseline, and baseline ADAS-Cog13 total score-by-visit interaction.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) ScoreBaseline, Week 78

The CDR-SB is a rater administered scale and impairment is scored in each of categories: memory, orientation, judgment and problem solving, community affairs, home and hobbies and personal care. Impairment is scored on a scale in which no dementia = 0, questionable dementia = 0.5, mild dementia = 1, moderate dementia = 2 and severe dementia = 3. The 6 individual category ratings, or "box scores", were added together to give the CDR-Sum of Boxes which ranges from 0-18, with higher scores indicating greater impairment. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline CDR-SB score, age at baseline, and baseline CDR-SB score-by-visit interaction.

Change From Baseline in Regional Cerebral Blood Flow (rCBF) Using Florbetapir Perfusion ScanBaseline, Week 78

Florbetapir perfusion evaluated the regional cerebral blood flow (rCBF) as a biomarker of brain function and was performed at the same time as the amyloid florbetapir PET. Cerebral perfusion, especially in temporal and parietal areas, is reduced in AD and this pattern of hypoperfusion closely mirrors the hypometabolism pattern observed using FDG PET. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF (last observation carried forward) and with factors for treatment, baseline biomarker and age at baseline.

Change From Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items Score (ADCS-iADL)Baseline, Week 78

The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADL score, age at baseline, and baseline iADL score-by-visit interaction.

Change From Baseline in Functional Activities Questionnaire (FAQ) ScoreBaseline, Week 78

FAQ is a 10-item, caregiver-based questionnaire and was administered to the study partner who was asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now=1; never did \[the activity\] but could do now=0; normal=0; has difficulty but does by self=1; requires assistance=2; Dependent =3). FAQ scale is 0 to 30, with higher scores indicating greater impairment. LS Mean determined by MMRM model with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline FAQ total score, by-visit interaction and age at baseline.

Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score StageFrom Loss of 1 Global Stage through Week 78

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 on the Integrated Alzheimer's Disease Rating Scale (iADRS) ScoreBaseline, Week 78

The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline iADRS13 total score, age at baseline, and baseline iADRS13 total score-by-visit interaction.

Change From Baseline in Neuropsychiatric Inventory (NPI) ScoreBaseline, Week 78

The NPI is a questionnaire administered to caregivers that quantifies behavioral changes. Each of the 12 behavioral domains the caregiver reports as present are scored for Frequency, scale: 1 (Occasionally) to 4 (Very Frequently), and Severity, scale: 1 (Mild) to 3 (Severe). If the domain is reported by the caregiver as 'Not Affected,' that domain is scored as 0. The individual domain scores are calculated by multiplying the frequency times the severity for each domain. NPI Total Score is calculated by adding the individual domain scores together for all 12 domains, with a scores range from 0 to 144, with higher scores indicating a greater severity of neuropsychiatric disturbance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline NPI score, age at baseline, and baseline NPI score-by-visit interaction.

Change From Baseline in CSF Biomarker Total TauBaseline, Week 71

Cerebrospinal fluid samples were collected for analysis of concentration total tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline.

Population Pharmacokinetics (PK): Apparent Oral Clearance of LanabecestatPredose, Week 4, 7, 19, 39, 45 and Week 71 post dose

The apparent oral clearance of lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis.

Change From Baseline on the Mini-Mental State Examination (MMSE)Baseline, Week 78

The MMSE is an instrument used to assess a participant's global cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment-by-visit interaction, AChEI use at baseline, pooled site, and covariates for baseline MMSE total score, age at baseline, and baseline MMSE total score-by-visit interaction.

Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40Baseline, Week 71

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 Biomarker Phosphorylated TauBaseline, Week 71

Cerebrospinal fluid samples are collected for analysis of concentration of phosphorylated tau. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline biomarker and age at baseline.

Change From Baseline in Whole Brain VolumeBaseline, Week 78

Magnetic resonance imaging (MRI) was used to evaluate the effect of lanabecestat on brain atrophy/whole brain volumes. Annualized change is derived as change at LOCF divided by (LOCF date - baseline date) multiplied by 365. LS Mean was determined by ANCOVA with LOCF and with factors for treatment, baseline volumetric magnetic resonance imaging (vMRI), intracranial volume and age at baseline.

Population PK: Central Volume of Distribution of LanabecestatPredose, Week 4, 7, 19, 39, 45 and week 71 post dose

The central volume of distribution for lanabecestat was estimated using a population approach. No covariate effects were assessed as part of this analysis.

Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42Baseline, Week 71

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.

Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) ScanBaseline, Week 78

Amyloid deposition in the brain is one of the defining neuropathologic findings of Alzheimer's disease. Florbetapir exhibits high affinity specific binding to amyloid plaques. The change from baseline was measured as average standard uptake value ratio (SUVr) in prespecified regions of interest (ROI) assessed by florbetapir amyloid PET imaging in a subset of participants. The Centiloid scale standardizes quantitative brain amyloid PET results to allow cross-tracer and cross-methodology comparisons. The Centiloid scale anchor points are 0 and 100, where 0 represents a high-certainty amyloid negative scan and 100 represents the amount of global amyloid deposition found in a typical AD scans. Florbetapir SUVr was converted to the Centiloid scale using the following conversion: Florbetapir Centiloids = 183 x SUVr - 177. LS Mean was determined by using ANCOVA methodology with terms for treatment, baseline biomarker and age at baseline.

Trial Locations

Locations (257)

Maine Neurology

🇺🇸

Scarborough, Maine, United States

Eastern Maine Medical Center

🇺🇸

Bangor, Maine, United States

Atlanta Center of Medical Research

🇺🇸

Atlanta, Georgia, United States

Care Access Research

🇺🇸

Valencia, California, United States

California Neuroscience Research

🇺🇸

Sherman Oaks, California, United States

Emory University

🇺🇸

Atlanta, Georgia, United States

Medical Research Health and Education Foundation, Inc

🇺🇸

Columbus, Georgia, United States

Raleigh Neurology Associates

🇺🇸

Raleigh, North Carolina, United States

Ohio State University Medical Center

🇺🇸

Columbus, Ohio, United States

Xenoscience

🇺🇸

Phoenix, Arizona, United States

California Research Foundation

🇺🇸

San Diego, California, United States

Pacific Research Network Inc

🇺🇸

San Diego, California, United States

Sharp Mesa Vista Hospital

🇺🇸

San Diego, California, United States

University of Miami

🇺🇸

Miami, Florida, United States

Allied Biomedical Research Institute, Inc.

🇺🇸

Miami, Florida, United States

Josephson Wallack Munshower Neurology

🇺🇸

Indianapolis, Indiana, United States

Boston University Medical Center

🇺🇸

Boston, Massachusetts, United States

Texas Medical Research Associates, L.L.C.

🇺🇸

San Antonio, Texas, United States

Chu De Nancy Hop D'Adultes De Brabois

🇫🇷

Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France

Mayo Clinic-Jacksonville

🇺🇸

Jacksonville, Florida, United States

Gregory A. Kirk MD LLC

🇺🇸

Merritt Island, Florida, United States

Donald S Marks

🇺🇸

Plymouth, Massachusetts, United States

Kawartha Regional Memory Clinic

🇨🇦

Peterborough, Ontario, Canada

Neuropsychiatric Research Center of Southwest Florida

🇺🇸

Fort Myers, Florida, United States

Four Peaks Neurology

🇺🇸

Scottsdale, Arizona, United States

Quantum Laboratories

🇺🇸

Pompano Beach, Florida, United States

Alzheimers Disease Center

🇺🇸

Winchester, Massachusetts, United States

Research Center for Clinical Studies, Inc

🇺🇸

Norwalk, Connecticut, United States

Brain Matters Research

🇺🇸

Delray Beach, Florida, United States

Ericksen Research and Development

🇺🇸

Clinton, Utah, United States

Klinikum der Universität München

🇩🇪

München, Bayern, Germany

Policlinico Univ. Agostino Gemelli

🇮🇹

Roma, Lazio, Italy

Himuro Neurology Clinic

🇯🇵

Osaka-Shi, Osaka-Fu, Japan

Ikeuchi Psycho Induced Internal Clinic

🇯🇵

Kobe-shi, Japan

Clinical Research Institute S C

🇲🇽

Tlalnepantla, Edo De Mex, Mexico

Korea University Anam Hospital

🇰🇷

Seoul, Korea, Republic of

Neurozentrum Sophienstraße

🇩🇪

Stuttgart, Baden-Württemberg, Germany

Cohen Medical Associates P.A.

🇺🇸

Delray Beach, Florida, United States

Memory Clinic Ochanomizu

🇯🇵

Bunkyo-ku, Tokyo, Japan

Aomori Prefectural Centeral Hospital

🇯🇵

Aomori, Japan

RSBIH Smolensk Regional Clinical Hospital

🇷🇺

Smolensk, Russian Federation

Intercoastal Medical Group

🇺🇸

Sarasota, Florida, United States

Charlton Lane Hospital

🇬🇧

Cheltenham, Gloucestershire, United Kingdom

True North Clinical Research Halifax, LLC

🇨🇦

Halifax, Nova Scotia, Canada

Institut Claude Pompidou - CMRR

🇫🇷

Nice, Alpes Maritimes, France

Toronto Sunnybrook Regional Cancer Center

🇨🇦

Toronto, Ontario, Canada

Klinikum Rechts der Isar der TU München

🇩🇪

München, Bayern, Germany

Dong-A University Medical Center

🇰🇷

Busan, Busan Gwang'yeogsi, Korea, Republic of

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

🇰🇷

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

Myongji Hospital

🇰🇷

Goyang-si, Gyeonggi-do, Korea, Republic of

Mexico Centre for Clinical Research SA de CV

🇲🇽

Mexico City, Distrito Federal, Mexico

FSBIH Siberian Clinical Center of FMBA

🇷🇺

Krasnoyarsk, Russian Federation

Ultramed

🇷🇺

Omsk, Russian Federation

Michigan State University

🇺🇸

East Lansing, Michigan, United States

University of Calgary

🇨🇦

Calgary, Alberta, Canada

Seoul National University Hospital

🇰🇷

Seoul, Korea, Republic of

CSSS-Institut Universitaire Gériatric de Sherbrooke

🇨🇦

Sherbrooke, Qubec, Canada

SDN - Istituto di Ricerca Diagnostica e Nucleare

🇮🇹

Napoli, Italy

Nara Medical University Hospital

🇯🇵

Kashihara, Nara, Japan

Kotobukikai Tominaga Clinic

🇯🇵

Osaka-shi, Osaka-Fu, Japan

NHO Hizen Psychiatric Center

🇯🇵

Kanzaki-gun, Saga-Ken, Japan

Juntendo University Hospital

🇯🇵

Bunkyo-ku, Tokyo, Japan

NHO Niigata Hospital

🇯🇵

Niigata, Japan

NHO Hokkaido Medical Center

🇯🇵

Sapporo-shi, Japan

EB Utrecht

🇳🇱

Utrecht, Netherlands

Konkuk University Hospital

🇰🇷

Seoul, Korea, Republic of

Praxis für Neurologie und Psychiatrie Dr. med. Roth

🇩🇪

Ostfildern, Baden-Württemberg, Germany

IRCCS Azienda Ospedaliera Universitaria San Martino

🇮🇹

Genova, Italy

Katayama Medical Clinic

🇯🇵

Kurashiki-shi, Okayama-Ken, Japan

Hospital Universitario de Saltillo

🇲🇽

Saltillo, Coahuila, Mexico

NZOZ Wroclawskie Centrum Alzheimerowskie

🇵🇱

Wroclaw, Dolnoslaskie, Poland

Uniwersyteckie Centrum Kliniczne

🇵🇱

Gdansk, Pomorskie, Poland

Klinika Neurologii Neuro-Care

🇵🇱

Katowice, Poland

Changhua Christian Hospital

🇨🇳

Changhua, Taiwan

Avix Investigación Clínica, S.C

🇲🇽

Monterrey, Nuevo León, Mexico

Instituto de Informacion en Salud Mental (INFOSAM)

🇲🇽

Monterrey, NL, Mexico

Centro de Estudios Clinicos y Esp Medicas SC

🇲🇽

Monterrey, Nuevo Leon, Mexico

Emotional Brain B.V.

🇳🇱

Almere, Netherlands

Amphia Ziekenhuis

🇳🇱

Breda, Netherlands

Clinsante Centrum Medyczne

🇵🇱

Torun, Poland

Cardinal Tien Hospital

🇨🇳

Sindian City, Taipei County, Taiwan

Hospital de Braga

🇵🇹

Braga, Portugal

Royal Devon and Exeter Hospital

🇬🇧

Exeter, Devon, United Kingdom

Re-Cognition Health Ltd

🇬🇧

London, United Kingdom

IRCCS Santa Lucia

🇮🇹

Roma, Italy

Neuro-Pain Medical Center

🇺🇸

Fresno, California, United States

St Josephs Hospital and Medical Center

🇺🇸

Phoenix, Arizona, United States

Center for Neurosciences

🇺🇸

Tucson, Arizona, United States

NEA Baptist Clinical

🇺🇸

Jonesboro, Arkansas, United States

The Research Center of Southern California

🇺🇸

Carlsbad, California, United States

Neurology Center of North Orange County

🇺🇸

Fullerton, California, United States

WCCT Global

🇺🇸

Costa Mesa, California, United States

Syrentis Clinical Research

🇺🇸

Santa Ana, California, United States

Associated Neurologists, PC - Danbury

🇺🇸

Danbury, Connecticut, United States

Morton Plant Hospital

🇺🇸

Clearwater, Florida, United States

JEM Research Institute

🇺🇸

Atlantis, Florida, United States

Indago Research & Health Center, Inc.

🇺🇸

Hialeah, Florida, United States

Infinity Clinical Research, LLC

🇺🇸

Hollywood, Florida, United States

Georgia Regents University

🇺🇸

Augusta, Georgia, United States

Jacksonville Center for Clinical Research

🇺🇸

Jacksonville, Florida, United States

Charlotte Neurological Services

🇺🇸

Port Charlotte, Florida, United States

American Health Network

🇺🇸

Muncie, Indiana, United States

Advanced Clinical Research LLC

🇺🇸

Meridian, Idaho, United States

Via Christi Research, Inc.

🇺🇸

Wichita, Kansas, United States

Cotton O'Neil Clinic

🇺🇸

Topeka, Kansas, United States

University of Kansas Hospital

🇺🇸

Fairway, Kansas, United States

Hattiesburg Clinic

🇺🇸

Hattiesburg, Mississippi, United States

Clinical Research Professionals

🇺🇸

Saint Louis, Missouri, United States

Butler Hospital

🇺🇸

Providence, Rhode Island, United States

Las Vegas Medical Research

🇺🇸

Las Vegas, Nevada, United States

New York University Medical Center

🇺🇸

New York, New York, United States

Behavioral Health Center Research

🇺🇸

Charlotte, North Carolina, United States

Advanced Memory Research Institute of New Jersey

🇺🇸

Toms River, New Jersey, United States

Neurology Specialists of Monmouth County

🇺🇸

West Long Branch, New Jersey, United States

Rapid Medical Research Inc

🇺🇸

Cleveland, Ohio, United States

Rhode Island Mood & Memory Research Institute

🇺🇸

East Providence, Rhode Island, United States

The Corvallis Clinic P.C.

🇺🇸

Corvallis, Oregon, United States

Holston Medical Group Clinical Research

🇺🇸

Kingsport, Tennessee, United States

Univ of North Texas Health Science Center

🇺🇸

Fort Worth, Texas, United States

Recherches Neuro-Hippocampe Inc

🇨🇦

Gatineau, Quebec, Canada

Toronto Memory Program

🇨🇦

Toronto, Ontario, Canada

Beijing 301 Hospital

🇨🇳

Beijing, Beijing, China

The Medical Arts Health Research Group

🇨🇦

West Vancouver, British Columbia, Canada

Xuanwu Hospital-Capital Medical University

🇨🇳

Beijing, Beijing, China

Douglas Hospital and Research Centre

🇨🇦

Verdun, Quebec, Canada

Q&T Research Sherbrooke Inc

🇨🇦

Sherbrooke, Quebec, Canada

Medical Services Prague s.r.o.

🇨🇿

Praha 6, Czechia

Nanjing Drum Tower Hosp Affiliated Hosp of Nanjing Univ Med

🇨🇳

Nanjing, Jiangsu, China

Shanghai Tongji Hospital(CCBR site)

🇨🇳

Shanghai, Shanghai, China

Tangshan Worker Hospital

🇨🇳

Tangshan, Hebei, China

Zhongda Hospital-Southeast University

🇨🇳

Nanjing, Jiangsu, China

CHU Saint Etienne - Hopital Nord

🇫🇷

Saint Priest en Jarez, Loire, France

CHU de Caen Hopital Cote de Nacre

🇫🇷

Caen Cedex, France

APHM Hôpital de la Timone

🇫🇷

Marseille, France

Diakoniekrankenhaus Henriettenstiftung Hannover

🇩🇪

Hannover, Niedersachsen, Germany

Praxis Dr. Erich Scholz

🇩🇪

Böblingen, Baden-Württemberg, Germany

A-Shine s.r.o.

🇨🇿

Plzen, Czechia

CHU Rennes/Hopital Sud

🇫🇷

Rennes Cedex, Ille Et Vilaine, France

CHU d'Amiens-Picardie Hopital Sud

🇫🇷

Amiens Cedex 1, France

Rigshospitalet

🇩🇰

Copenhagen, Denmark

CHU Strasbourg Hôpital de Hautepierre

🇫🇷

Strasbourg Cedex, France

Neuropraxis München Süd

🇩🇪

Unterhaching, Bayern, Germany

MVZ LiO Berlin

🇩🇪

Berlin, Germany

Ente Ospedaliero Ospedali Galliera

🇮🇹

Genova, Italy

Azienda Ospedaliera - Universitaria Pisana

🇮🇹

Pisa, Italy

Nagoya Ekisaikai Hospital

🇯🇵

Nagoya-shi, Aichi-Ken, Japan

Kojunkai Daido Hospital

🇯🇵

Nagoya-Shi, Aichi-Ken, Japan

Koseikai Kusatsu Hospital

🇯🇵

Hiroshima-shi, Hiroshima-Ken, Japan

Azienda Ospedaliera Citta della Salute della Scienza Torino

🇮🇹

Torino, Italy

Universita La Sapienza

🇮🇹

Roma, Italy

Inage Neurology and Memory Clinic

🇯🇵

Chiba-shi, Chiba-Ken, Japan

Jisenkai Nanko Psychiatric Institute

🇯🇵

Shirakawa-shi, Fukushima-Ken, Japan

Uji Takeda Hospital

🇯🇵

Uji-Shi, Kyoto-Fu, Japan

Ehime University Hospital

🇯🇵

Toon-Shi, Ehime-Ken, Japan

JADECOM Nara City Hospital

🇯🇵

Nara-Shi, Nara-Ken, Japan

Takeda General Hospital

🇯🇵

Aizu-Wakamatsu, Fukushima, Japan

NHO Hiroshima-Nishi Medical Center

🇯🇵

Otaki-Shi, Hiroshima-Ken, Japan

Koseikai Takeda Hospital

🇯🇵

Kyoto-Shi, Kyoto-Fu, Japan

Shimizu Hospital

🇯🇵

Shizuoka-shi, Shizuoka, Japan

Yokohama Hospital

🇯🇵

Yokohama, Kanagawa, Japan

Kousaiin Hospital

🇯🇵

Suita-shi, Osaka-Fu, Japan

Oita University Hospital

🇯🇵

Yufu-shi, Oita-Ken, Japan

Musashino Red Cross Hospital

🇯🇵

Musashino, Tokyo, Japan

Keikokai P-One Clinic

🇯🇵

Hachioji-shi, Tokyo-To, Japan

Inha University Hospital

🇰🇷

Incheon, Korea, Republic of

JOHAS Sanin Rosai Hospital

🇯🇵

Yonago-shi, Tottori-Ken, Japan

Seoul National University Bundang Hospital

🇰🇷

Seongnam-si, Gyeonggi-do, Korea, Republic of

Hospital Univ. Jose Eleuterio Gonzalez

🇲🇽

Monterrey, N.l., Mexico

Hanyang University Medical Center

🇰🇷

Seoul, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Isala Klinieken

🇳🇱

Zwolle, Netherlands

Podlaskie Centrum Psychogeriatrii

🇵🇱

Białystok, Podlaskie, Poland

Brain Research Center

🇳🇱

Amsterdam, Netherlands

NZOZ Mach-Med

🇵🇱

Chorzow, Poland

Globe Badania Kliniczne SP Z O.O.

🇵🇱

Klodzko, Poland

Prywatny Gabinet Lekarski U.Chyrchel

🇵🇱

Lublin, Poland

Centrum Medyczne Medyk

🇵🇱

Rzeszow, Poland

Euromedis Sp. z o.o.

🇵🇱

Szczecin, Poland

Hospitals da Universidade de Coimbra

🇵🇹

Coimbra, Portugal

SAIH Republ. Clinical Hospital of the MoH of Republ. Tatarst

🇷🇺

Kazan, Russian Federation

Centrum Medyczne

🇵🇱

Warszawa, Poland

Specjalistyczny Osrodek Medycyny Wieku Dojrzalego SOMED

🇵🇱

Warszawa, Poland

Hospital Fernando Fonseca

🇵🇹

Amadora, Portugal

SIH Kemerovo Regional Clinical Hosptial

🇷🇺

Kemerovo, Russian Federation

Hospital Cardiovascular San Vicente

🇪🇸

San Vicente del Raspeig, Alicante, Spain

LLC City Neurological Centre Sibneuromed

🇷🇺

Novosibirsk, Russian Federation

LLC Treatment and Rehabilitation

🇷🇺

Rostov-on-Don, Russian Federation

Hospital General de Catalunya

🇪🇸

Sant Cugat del Valles, Barcelona, Spain

Novosibirsk State Medical University

🇷🇺

Novosibirsk, Russian Federation

Hospital Ntra Sra Perpetuo Socorro

🇪🇸

Albacete, Spain

Bekhterev Psyconeurological Institute

🇷🇺

St. Petersburg, Russian Federation

Central Medical Sanitary Hospital #122

🇷🇺

St. Petersburg, Russian Federation

Regional State Institution of Healthcare Tomsk Clinica Psych

🇷🇺

Tomsk, Russian Federation

National Taiwan University Hospital

🇨🇳

Douliu, Yunlin County, Taiwan

Chang Gung Memorial Hospital - Linkou

🇨🇳

Taoyuan City, Taiwan

Taipei Veterans General Hospital

🇨🇳

Taipei, Taiwan

Hospital del Mar

🇪🇸

Barcelona, Spain

Policlinica Guipuzcoa

🇪🇸

Donostia, Guipuzcoa, Spain

Fundacion ACE-Institut Catala de Neurociences Aplicades

🇪🇸

Barcelona, Spain

Kaohsiung Medical University Chung-Ho Memorial Hospital

🇨🇳

Kaohsiung, Taiwan

National Cheng Kung University Hospital

🇨🇳

Tainan, Taiwan

Chang Gung Memorial Hospital - Kaohsiung

🇨🇳

Kaohsiung, Taiwan

Taipei Medical University- Shuang Ho Hospital

🇨🇳

New Taipei, Taiwan

Victoria Centre

🇬🇧

Swindon, Wiltshire, United Kingdom

Glasgow Memory Clinic

🇬🇧

Glasgow, United Kingdom

Lynn Health Science Institute

🇺🇸

Oklahoma City, Oklahoma, United States

Cutting Edge Research Group

🇺🇸

Oklahoma City, Oklahoma, United States

Summit Research Network Inc

🇺🇸

Portland, Oregon, United States

Murray Royal Hospital

🇬🇧

Perth, Tayside Region, United Kingdom

Axiom Research

🇺🇸

Tampa, Florida, United States

University of South Florida

🇺🇸

Tampa, Florida, United States

Hospital Universitario La Fe de Valencia

🇪🇸

Valencia, Spain

Institute for Neurodegenerative Disorders

🇺🇸

New Haven, Connecticut, United States

Compass Research

🇺🇸

Orlando, Florida, United States

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

PMG Research of Winston-Salem, LLC

🇺🇸

Winston-Salem, North Carolina, United States

Wake Forest Baptist Univ CAR

🇺🇸

Winston-Salem, North Carolina, United States

Arizona Neurology

🇺🇸

Scottsdale, Arizona, United States

Pacific Neuroscience Medical Group

🇺🇸

Oxnard, California, United States

Pearl Clinical Research Inc.

🇺🇸

Norristown, Pennsylvania, United States

Insight Clinical Trials

🇺🇸

Shaker Heights, Ohio, United States

Clinical Trial Center, LLC, Psychiatry

🇺🇸

Jenkintown, Pennsylvania, United States

Guangzhou First People's Hospital

🇨🇳

Guangzhou, Guangdong, China

Qingdao Municipal Hospital

🇨🇳

Qingdao, Shandong, China

Northern Jiangsu People's Hospital

🇨🇳

Yangzhou, Jiangsu, China

Shanghai Huashan Hospital Affil to Fu Dan University

🇨🇳

Shanghai, China

The First Affiliated Hospital of Wenzhou Medical College

🇨🇳

Wenzhou, Zhejiang, China

West China Hospital of Sichuan University

🇨🇳

Chengdu, Sichuan, China

The First Affiliated Hospital, Zhejiang University

🇨🇳

Hangzhou, Zhejiang, China

Fakultni nemocnice u sv. Anny v Brne

🇨🇿

Brno, Czechia

Neurohk s.r.o.

🇨🇿

Chocen, Czechia

Brain-Soultherapy s.r.o

🇨🇿

Kladno, Czechia

Neuropsychiatrie s.r.o

🇨🇿

Praha 6, Czechia

Axon Clinical, s.r.o.

🇨🇿

Praha 8, Czechia

CCBR-Alborg-DK

🇩🇰

Aalborg, Denmark

Clintrial, s.r.o.

🇨🇿

Praha 10, Czechia

Center for Clinical and Basic Research -CCBR

🇩🇰

Vejle, Denmark

Center For Clinical and Basic Research

🇩🇰

Ballerup, Denmark

Chu de Toulouse Hopital de La Grave

🇫🇷

Toulouse Cedex, France

ISPG - Institut für Studien zur psychischen Gesundheit

🇩🇪

Mannheim, Baden-Württemberg, Germany

Spedali Civili - Universita degli Studi

🇮🇹

Brescia, Italy

Azienda Ospedaliera Universitaria Careggi

🇮🇹

Firenze, Italy

Shinwakai Yachiyo Hospital

🇯🇵

Anjo-shi, Aichi-Ken, Japan

Yuge Hospital

🇯🇵

Kumamoto, Japan

Accelerium Clinical Research

🇲🇽

Monterrey, Nuevo Leon, Mexico

Hawaii Medical Center

🇺🇸

Honolulu, Hawaii, United States

Baptist Health Medical Group

🇺🇸

Lexington, Kentucky, United States

Associates in Neurology, PSC

🇺🇸

Lexington, Kentucky, United States

Medical University of South Carolina

🇺🇸

Charleston, South Carolina, United States

SSM Health Dean Medical Group

🇺🇸

Madison, Wisconsin, United States

Bruyere Continuing Care

🇨🇦

Ottawa, Ontario, Canada

Coastal Neurology PA

🇺🇸

Port Royal, South Carolina, United States

Hôpital de la Pitié-Salpêtrière

🇫🇷

Paris, France

Hospital Mutua de Terrassa

🇪🇸

Terrassa, Barcelona, Spain

Hospital Virgen Del Puerto

🇪🇸

Plasencia, Caceres, Spain

Rhode Island Hospital

🇺🇸

Providence, Rhode Island, United States

Radiant Research

🇺🇸

Greer, South Carolina, United States

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