A Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease Dementia
- Registration Number
- NCT02972658
- Lead Sponsor
- AstraZeneca
- Brief Summary
This study is an extension of study I8D-MC-AZES (NCT02245737), the AMARANTH study. The purpose of this study is to evaluate the effectiveness of the study drug lanabecestat in participants with early Alzheimer's disease dementia at the time of entry into study I8D-MC-AZES.
- Detailed Description
Study AZFD was designed to be integrated with 104-week study AZES to form a Delayed-Start study (Study AZES-FD). Study AZES-FD was to be used to test the hypothesis that participants originally randomized to receive placebo in the double-blind feeder study AZES and switched to LY3314814 at the start of study AZFD did not "catch up" on the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog13) at Week 26 of study AZFD to participants originally randomized to receive LY3314814 in the double-blind feeder study.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 421
- Participants previously enrolled in AMARANTH (NCT02245737) who meet eligibility criteria for delayed-start I8D-MC-AZFD.
- Participants who participate in AMARANTH (NCT02245737) who develop new conditions precluding them from enrolling into I8D-MC-AZFD.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description AZES Lanabecestat 20 milligrams (mg)/AZFD Lanabecestat 20 mg Lanabecestat Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. AZES Placebo/AZFD Lanabecestat 50 mg Lanabecestat Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg Lanabecestat Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. AZES Placebo/AZFD Lanabecestat 20 mg Lanabecestat Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.
- Primary Outcome Measures
Name Time Method Change From Baseline Analysis on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) AZES Baseline through AZFD Week 26 ADAS-Cog13 (13-item version of ADAS-Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment\*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, apolipoprotein E4 (APOE4) status, acetylcholinesterase inhibitor (AChEI) use at baseline, age at baseline, and pooled country.
- Secondary Outcome Measures
Name Time Method Change From Baseline Analysis on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL) AZES Baseline through AZFD Week 26 The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM with factors for treatment, visit, treatment\*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Change From Baseline on the Functional Activities Questionnaire (FAQ) Score AZES Baseline through AZFD Week 26 FAQ is a 10-item, caregiver-questionnaire and was administered to the study partner and asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now =1; Never did but could do now =0; Normal =0; Has difficulty but does by self =1; Requires assistance =2; Dependent =3). FAQ scale is 0 to 30, with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment\*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score AZES Baseline through AZFD Week 26 The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment\*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Change From Baseline on the Mini-Mental Status Examination (MMSE) AZES Baseline through AZFD Week 26 The MMSE is an instrument used to assess a participant's cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment\*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Change From Baseline Analysis on the ADAS-Cog13 AZES Baseline through AZFD Week 52 ADAS-cog13 (13-item ADAS cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment\*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.
Trial Locations
- Locations (129)
Brain Matters Research
🇺🇸Delray Beach, Florida, United States
IMIC, Inc.
🇺🇸Palmetto Bay, Florida, United States
Suncoast Neuroscience Associates
🇺🇸Saint Petersburg, Florida, United States
Community Clinical Research Center
🇺🇸Anderson, Indiana, United States
Universitätsklinikum Köln
🇩🇪Köln, Nordrhein-Westfalen, Germany
Charité Universitätsmedizin Berlin
🇩🇪Berlin, Germany
The University of Tokyo Hospital
🇯🇵Bunkyo-ku, Tokyo, Japan
NZOZ Dom Sue Ryder - Pallmed Sp. z o.o.
🇵🇱Bydgoszcz, Poland
Centrum Medyczne Neuroprotect
🇵🇱Warszawa, Poland
Hospital De La Princesa
🇪🇸Madrid, Spain
Hospital Universitario La Fe de Valencia
🇪🇸Valencia, Spain
Hospital Universitario Dr Pesset
🇪🇸Valencia, Spain
MAC Clinical Research-Manchester
🇬🇧Manchester, Greater Manchester, United Kingdom
West London Mental Health NHS Trust
🇬🇧Isleworth, London, United Kingdom
Glasgow Memory Clinic
🇬🇧Glasgow, United Kingdom
Australian Alzheimer's Research Foundation
🇦🇺Nedlands, Western Australia, Australia
The Multiple Sclerosis Center of Atlanta
🇺🇸Atlanta, Georgia, United States
University of Chicago Medical Center
🇺🇸Chicago, Illinois, United States
Integrative Clinical Trials, LLC
🇺🇸Brooklyn, New York, United States
Ohio State University Medical Center
🇺🇸Columbus, Ohio, United States
Banner Alzheimer's Institute
🇺🇸Phoenix, Arizona, United States
Pacific Research Network Inc
🇺🇸San Diego, California, United States
Mile High Research Center
🇺🇸Denver, Colorado, United States
Lindner Research Center
🇺🇸Cincinnati, Ohio, United States
Cliniques Universitaires Saint-Luc
🇧🇪Brussels, Belgium
Georgetown University Medical Center
🇺🇸Washington, District of Columbia, United States
Hospital Universitaire Erasme Brussel
🇧🇪Brussel, Belgium
Klinikum Rechts der Isar der TU München
🇩🇪München, Bayern, Germany
Gemeinschaftspraxis für Neurologie und Psychiatrie
🇩🇪Westerstede, Niedersachsen, Germany
DataMed Klinische Studien GmbH
🇩🇪Köln, Nordrhein-Westfalen, Germany
Katayama Medical Clinic
🇯🇵Kurashiki, Okayama, Japan
Shiroma Clinic
🇯🇵Urasoe, Okinawa, Japan
Utano Hospital
🇯🇵Kyoto, Japan
Osaka City University Hospital
🇯🇵Osaka, Japan
Inha University Hospital
🇰🇷Junggu, Incheon, Korea, Republic of
Gachon University Gil Medical Center
🇰🇷Incheon, Korea, Republic of
Podlaskie Centrum Psychogeriatrii
🇵🇱Białystok, Podlaskie, Poland
SC Centrul Medical Sana SRL
🇷🇴Bucuresti, Romania
Hospital Universitari de Bellvitge
🇪🇸Hospitalet de Llobregat, Barcelona, Spain
Advanced Memory Research Institute of New Jersey
🇺🇸Toms River, New Jersey, United States
Okanagan Clinical Trials
🇨🇦Kelowna, British Columbia, Canada
Tokyo Women's Medical University Hospital
🇯🇵Shinjuku-ku, Tokyo, Japan
The Cognitive and Research Center of NJ
🇺🇸Springfield, New Jersey, United States
Hôpital Fernand Widal
🇫🇷Paris, France
Roskamp Institute
🇺🇸Sarasota, Florida, United States
AZ Delta
🇧🇪Roeselare, Belgium
Hopital Neuro Pierre Wertheimer
🇫🇷Bron Cedex, France
Tsukuba University Hospital
🇯🇵Tsukuba, Ibaraki, Japan
Iwate Medical University Hospital
🇯🇵Morioka, Iwate, Japan
Nippon Medical School Hospital
🇯🇵Bunkyo-Ku, Tokyo, Japan
Fukuoka University Hospital
🇯🇵Fukuoka, Japan
Memory Enhancement Center of America, Inc.
🇺🇸Eatontown, New Jersey, United States
SE Neurologiai Klinika
🇭🇺Budapest, Hungary
Premiere Research Institute at Palm Beach Neurology
🇺🇸West Palm Beach, Florida, United States
Jessa Ziekenhuis
🇧🇪Hasselt, Limburg, Belgium
Hanyang University Guri Hospital
🇰🇷Guri-si, Gyeonggido, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Korea, Republic of
NZOZ Wielospecjalistyczna Poradnia Lekarska
🇵🇱Katowice, Poland
Elizabeth Bruyere Health Centre
🇨🇦Ottawa, Ontario, Canada
Quillen College of Medicine, East TN State University
🇺🇸Johnson City, Tennessee, United States
Hattiesburg Clinic
🇺🇸Hattiesburg, Mississippi, United States
Hopital de L'Enfant Jesus
🇨🇦Quebec City, Quebec, Canada
Nihon Kokan Hospital
🇯🇵Kawasaki, Kanagawa, Japan
National Sanatorium Toneyama Hospital
🇯🇵Toyonaka, Osaka, Japan
Medycyna Milorzab
🇵🇱Lodz, Poland
Instytut Medycyny Wsi
🇵🇱Lublin, Poland
Santa Cruz Behavioral PSC
🇵🇷Bayamón, Puerto Rico
Boston Center for Memory
🇺🇸Newton, Massachusetts, United States
Centre Hospitalier Universitaire La Timone
🇫🇷Marseille, Cedex 05, France
CHU de Toulouse Hopital Purpan
🇫🇷Toulouse, Cedex, France
Hopital des Charpennes
🇫🇷Villeurbanne, France
Neurologische Praxis Siegen
🇩🇪Siegen, Nordrhein-Westfalen, Germany
Pharm Studienzentrum Chemnitz
🇩🇪Mittweida, Sachsen, Germany
Toronto Memory Program
🇨🇦Toronto, Ontario, Canada
Sakaguchi Clinic
🇯🇵Sakai, Osaka, Japan
Memory Clinic Ochanomizu
🇯🇵Bunkyo-ku, Tokyo, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Dong-A University Medical Center
🇰🇷Seogu, Busan, Korea, Republic of
True North Clinical Research Halifax, LLC
🇨🇦Halifax, Nova Scotia, Canada
Universitätsklinikum Ulm
🇩🇪Ulm, Baden-Württemberg, Germany
Krakowska Akademia Neurologii
🇵🇱Krakow, Poland
Hospital General Universitario de Elche
🇪🇸Elche, Alicante, Spain
Hospital Virgen Del Puerto
🇪🇸Plasencia, Caceres, Spain
Territory Neurology & Research Institute
🇺🇸Tucson, Arizona, United States
Valley Medical Primary Care
🇺🇸Centerville, Ohio, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
University of Rochester School of Medicine
🇺🇸Rochester, New York, United States
The Memory Clinic
🇺🇸Bennington, Vermont, United States
Lehigh Valley Hospital
🇺🇸Allentown, Pennsylvania, United States
Southern Neurology
🇦🇺Kogarah, New South Wales, Australia
Eastern Clinical Research Unit
🇦🇺Box Hill, Victoria, Australia
Delmont Private Hospital
🇦🇺Glen Iris, Victoria, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
The Florey Institute of Neuroscience and Mental Health
🇦🇺Parkville, Victoria, Australia
Neuro Trials Victoria Pty Ltd
🇦🇺Noble Park, Australia
Hopital Universitaire Brugmann Brussel
🇧🇪Brussels, Belgium
Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Kawartha Regional Memory Clinic
🇨🇦Peterborough, Ontario, Canada
NeuroSearch Developements
🇨🇦Greenfield Park, Quebec, Canada
Q&T Research Sherbrooke Inc
🇨🇦Sherbrooke, Quebec, Canada
CHRU de Lille- Hôpital Roger Salengro
🇫🇷Lille, Cedex, France
Hôpital de la Pitié-Salpêtrière
🇫🇷Paris, France
CHU Bocage CMRR
🇫🇷Dijon, France
Hopital Broca
🇫🇷Paris, France
Centre de Recherche Clinique du Gérontopôle Cité de la Santé
🇫🇷Toulouse, France
Studien und Gedächtniszentrum München
🇩🇪München, Bayern, Germany
Chu de Nantes Hopital Laennec
🇫🇷Saint-Herblain, France
National Institute for Longevity Sciences NCGG
🇯🇵Obu, Aichi, Japan
National Chiba-East-Hospital
🇯🇵Chuo-ku, Chiba, Japan
National Sanatorium Hokuriku Hospital
🇯🇵Nanto, Toyama, Japan
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul St. Mary's Hospital
🇰🇷Seoul, Korea, Republic of
Centrum Zdrowia Psychicznego Biomed - Jan Latala
🇵🇱Kielce, Poland
SC Med Life SA
🇷🇴Bucuresti, Romania
Hospital Universitario De Getafe
🇪🇸Madrid, Getafe, Spain
Fundacion ACE-Institut Catala de Neurociences Aplicades
🇪🇸Barcelona, Spain
CITA Alzheimer
🇪🇸San Sebastian, Guipuzcoa, Spain
Centro de Atencion Especializada (CAE) OROITU
🇪🇸Getxo, Vizcaya, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Hospital Son Espases
🇪🇸Palma De Mallorca, Spain
Hospital Santa Creu I Sant Pau
🇪🇸Barcelona, Spain
Re-Cognition Health Ltd
🇬🇧Guildford, Surrey, United Kingdom
MAC Clinical Research
🇬🇧Leeds, United Kingdom
Hospital Clinic I Provincial
🇪🇸Barcelona, Spain
Institute for Neurodegenerative Disorders
🇺🇸New Haven, Connecticut, United States
Compass Research
🇺🇸Orlando, Florida, United States
Rhode Island Mood & Memory Research Institute
🇺🇸East Providence, Rhode Island, United States
Clinique de la Memoire de l'Outaouais
🇨🇦Gatineau, Quebec, Canada
Radiant Research
🇺🇸Greer, South Carolina, United States