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

Alzheimer's Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02972658
• Other study ID #: 16557
• Secondary ID: I8D-MC-AZFD2016-
• Status: Terminated
• Phase: Phase 3
• Start date: March 15, 2017
• Est. completion date: October 2, 2018

Study information

• Verified date: November 2019
• Source: AstraZeneca
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 421
• Est. completion date: October 2, 2018
• Est. primary completion date: October 2, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

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

Related Conditions & MeSH terms

• Alzheimer Disease
• Alzheimer's Disease
• Dementia

Intervention

Drug:
• Lanabecestat
Administered orally

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Australia	Eastern Clinical Research Unit	Box Hill	Victoria
Australia	Delmont Private Hospital	Glen Iris	Victoria
Australia	Southern Neurology	Kogarah	New South Wales
Australia	Australian Alzheimer's Research Foundation	Nedlands	Western Australia
Australia	Neuro Trials Victoria Pty Ltd	Noble Park
Australia	The Florey Institute of Neuroscience and Mental Health	Parkville	Victoria
Belgium	Hospital Universitaire Erasme Brussel	Brussel
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Belgium	Hopital Universitaire Brugmann Brussel	Brussels
Belgium	Jessa Ziekenhuis	Hasselt	Limburg
Belgium	Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg	Leuven
Belgium	AZ Delta	Roeselare
Canada	Clinique de la Memoire de l'Outaouais	Gatineau	Quebec
Canada	NeuroSearch Developements	Greenfield Park	Quebec
Canada	True North Clinical Research Halifax, LLC	Halifax	Nova Scotia
Canada	Okanagan Clinical Trials	Kelowna	British Columbia
Canada	Elizabeth Bruyere Health Centre	Ottawa	Ontario
Canada	Kawartha Regional Memory Clinic	Peterborough	Ontario
Canada	Hopital de L'Enfant Jesus	Quebec City	Quebec
Canada	Q&T Research Sherbrooke Inc	Sherbrooke	Quebec
Canada	Toronto Memory Program	Toronto	Ontario
France	Hopital Neuro Pierre Wertheimer	Bron Cedex
France	CHU Bocage CMRR	Dijon
France	CHRU de Lille- Hôpital Roger Salengro	Lille	Cedex
France	Centre Hospitalier Universitaire La Timone	Marseille	Cedex 05
France	Hopital Broca	Paris
France	Hôpital de la Pitié-Salpêtrière	Paris
France	Hôpital Fernand Widal	Paris
France	Chu de Nantes Hopital Laennec	Saint-Herblain
France	Centre de Recherche Clinique du Gérontopôle Cité de la Santé	Toulouse
France	CHU de Toulouse Hopital Purpan	Toulouse	Cedex
France	Hopital des Charpennes	Villeurbanne
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	Charité Universitätsmedizin Berlin	Berlin
Germany	DataMed Klinische Studien GmbH	Köln	Nordrhein-Westfalen
Germany	Universitätsklinikum Köln	Köln	Nordrhein-Westfalen
Germany	Pharm Studienzentrum Chemnitz	Mittweida	Sachsen
Germany	Klinikum Rechts der Isar der TU München	München	Bayern
Germany	Studien und Gedächtniszentrum München	München	Bayern
Germany	Neurologische Praxis Siegen	Siegen	Nordrhein-Westfalen
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Germany	Gemeinschaftspraxis für Neurologie und Psychiatrie	Westerstede	Niedersachsen
Hungary	SE Neurologiai Klinika	Budapest
Japan	Memory Clinic Ochanomizu	Bunkyo-ku	Tokyo
Japan	Nippon Medical School Hospital	Bunkyo-Ku	Tokyo
Japan	The University of Tokyo Hospital	Bunkyo-ku	Tokyo
Japan	National Chiba-East-Hospital	Chuo-ku	Chiba
Japan	Fukuoka University Hospital	Fukuoka
Japan	Nihon Kokan Hospital	Kawasaki	Kanagawa
Japan	Katayama Medical Clinic	Kurashiki	Okayama
Japan	Kyoto University Hospital	Kyoto
Japan	Utano Hospital	Kyoto
Japan	Iwate Medical University Hospital	Morioka	Iwate
Japan	National Sanatorium Hokuriku Hospital	Nanto	Toyama
Japan	National Institute for Longevity Sciences NCGG	Obu	Aichi
Japan	Osaka City University Hospital	Osaka
Japan	Sakaguchi Clinic	Sakai	Osaka
Japan	Tokyo Women's Medical University Hospital	Shinjuku-ku	Tokyo
Japan	National Sanatorium Toneyama Hospital	Toyonaka	Osaka
Japan	Tsukuba University Hospital	Tsukuba	Ibaraki
Japan	Shiroma Clinic	Urasoe	Okinawa
Korea, Republic of	Hanyang University Guri Hospital	Guri-si	Gyeonggido
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Inha University Hospital	Junggu	Incheon
Korea, Republic of	Dong-A University Medical Center	Seogu	Busan
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul	Korea
Korea, Republic of	Seoul St. Mary's Hospital	Seoul
Poland	Podlaskie Centrum Psychogeriatrii	Bialystok	Podlaskie
Poland	NZOZ Dom Sue Ryder - Pallmed Sp. z o.o.	Bydgoszcz
Poland	NZOZ Wielospecjalistyczna Poradnia Lekarska	Katowice
Poland	Centrum Zdrowia Psychicznego Biomed - Jan Latala	Kielce
Poland	Krakowska Akademia Neurologii	Krakow
Poland	Medycyna Milorzab	Lodz
Poland	Instytut Medycyny Wsi	Lublin
Poland	Centrum Medyczne Neuroprotect	Warszawa
Puerto Rico	Santa Cruz Behavioral PSC	Bayamón
Romania	SC Centrul Medical Sana SRL	Bucuresti
Romania	SC Med Life SA	Bucuresti
Spain	Fundacion ACE-Institut Catala de Neurociences Aplicades	Barcelona
Spain	Hospital Clinic I Provincial	Barcelona
Spain	Hospital Santa Creu I Sant Pau	Barcelona
Spain	Hospital General Universitario de Elche	Elche	Alicante
Spain	Centro de Atencion Especializada (CAE) OROITU	Getxo	Vizcaya
Spain	Hospital Universitari de Bellvitge	Hospitalet de Llobregat	Barcelona
Spain	Hospital De La Princesa	Madrid
Spain	Hospital Universitario De Getafe	Madrid	Getafe
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Son Espases	Palma De Mallorca
Spain	Hospital Virgen Del Puerto	Plasencia	Caceres
Spain	CITA Alzheimer	San Sebastian	Guipuzcoa
Spain	Hospital Universitario Dr Pesset	Valencia
Spain	Hospital Universitario La Fe de Valencia	Valencia
United Kingdom	MAC Clinical Research	Blackpool	Lancashire
United Kingdom	MAC Clinical Research	Cannock	Staffordshire
United Kingdom	Glasgow Memory Clinic	Glasgow
United Kingdom	Re-Cognition Health Ltd	Guildford	Surrey
United Kingdom	West London Mental Health NHS Trust	Isleworth	London
United Kingdom	MAC Clinical Research	Leeds
United Kingdom	Re-Cognition Health Ltd	London	Greater London
United Kingdom	MAC Clinical Research-Manchester	Manchester	Greater Manchester
United States	Lehigh Valley Hospital	Allentown	Pennsylvania
United States	Community Clinical Research Center	Anderson	Indiana
United States	The Multiple Sclerosis Center of Atlanta	Atlanta	Georgia
United States	The Memory Clinic	Bennington	Vermont
United States	Integrative Clinical Trials, LLC	Brooklyn	New York
United States	Valley Medical Primary Care	Centerville	Ohio
United States	University of Chicago Medical Center	Chicago	Illinois
United States	Lindner Research Center	Cincinnati	Ohio
United States	Ohio State University Medical Center	Columbus	Ohio
United States	Brain Matters Research	Delray Beach	Florida
United States	Mile High Research Center	Denver	Colorado
United States	Rhode Island Mood & Memory Research Institute	East Providence	Rhode Island
United States	Memory Enhancement Center of America, Inc.	Eatontown	New Jersey
United States	Radiant Research	Greer	South Carolina
United States	Hattiesburg Clinic	Hattiesburg	Mississippi
United States	Quillen College of Medicine, East TN State University	Johnson City	Tennessee
United States	Institute for Neurodegenerative Disorders	New Haven	Connecticut
United States	Columbia University Medical Center	New York	New York
United States	Boston Center for Memory	Newton	Massachusetts
United States	Compass Research	Orlando	Florida
United States	IMIC, Inc.	Palmetto Bay	Florida
United States	Banner Alzheimer's Institute	Phoenix	Arizona
United States	University of Rochester School of Medicine	Rochester	New York
United States	Suncoast Neuroscience Associates	Saint Petersburg	Florida
United States	Pacific Research Network Inc	San Diego	California
United States	Roskamp Institute	Sarasota	Florida
United States	The Cognitive and Research Center of NJ	Springfield	New Jersey
United States	Advanced Memory Research Institute of New Jersey	Toms River	New Jersey
United States	Territory Neurology & Research Institute	Tucson	Arizona
United States	Georgetown University Medical Center	Washington	District of Columbia
United States	Premiere Research Institute at Palm Beach Neurology	West Palm Beach	Florida

Sponsors (2)

Lead Sponsor	Collaborator
AstraZeneca	Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Germany,  Hungary,  Japan,  Korea, Republic of,  Poland,  Puerto Rico,  Romania,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline Analysis on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)	ADAS-Cog13 (13-item version of ADAS-Cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, apolipoprotein E4 (APOE4) status, acetylcholinesterase inhibitor (AChEI) use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
Secondary	Change From Baseline Analysis on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL)	The ADCS-ADL is a 23-item inventory developed as a rater-administered questionnaire answered by the participant's caregiver. The ADCS-ADL measures both basic and instrumental activities of daily living by participants. The range for the ADCS-iADL is 0-59 with higher scores reflecting better performance. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
Secondary	Change From Baseline on the Functional Activities Questionnaire (FAQ) Score	FAQ is a 10-item, caregiver-questionnaire and was administered to the study partner and asked to rate the participant's ability to perform a variety of activities ranging from writing checks, assembling tax records, shopping, playing games, food preparation, traveling, keeping appointments, traveling out of neighborhood, keeping track of current events and understanding media. FAQ total score was calculated by adding the scores from each of the 10 items. Each activity is rated on a scale from 0 to 3 (Never did and would have difficulty now =1; Never did but could do now =0; Normal =0; Has difficulty but does by self =1; Requires assistance =2; Dependent =3). FAQ scale is 0 to 30, with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
Secondary	Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score	The iADRS is a composite that measures both cognition and function. The iADRS comprises scores form the ADAS- Cog and the ADCS-iADL. The iADRS is calculated as a linear combination of the total scores of the ADAS-Cog13 (score range 0 to 85 with higher scores reflecting worse performance) and the ADCS-iADL (score range from 0-59 with higher scores reflecting better performance). The iADRS score ranges from 0 to 144 with higher scores indicating greater impairment. LS Mean was determined by MMRM with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
Secondary	Change From Baseline on the Mini-Mental Status Examination (MMSE)	The MMSE is an instrument used to assess a participant's cognitive function. The MMSE assesses orientation to time and place, immediate and delayed recall of words, attention and calculation, language (naming, comprehension and repetition), and spatial ability (copying a figure). The range for MMSE total Score is 0 to 30, with a higher score indicating better cognitive performance. LS Mean was determined by MMRM methodology with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 26
Secondary	Change From Baseline Analysis on the ADAS-Cog13	ADAS-cog13 (13-item ADAS cog) is a psychometric instrument that evaluates word recall, ability to follow commands, constructional praxis, naming, ideational praxis, orientation, word recognition, memory, comprehension of spoken language, word-finding, and language ability, with a measure of delayed word recall and concentration/ distractibility. The total score of the 13-item scale ranges from 0 to 85, with an increase in score indicating cognitive worsening. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with factors for treatment, visit, treatment*visit, baseline efficacy score, baseline efficacy score-by-visit interaction, disease status at baseline, APOE4 status, AChEI use at baseline, age at baseline, and pooled country.	AZES Baseline through AZFD Week 52

External Links

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