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| ID | Type | Description | Link |
|---|---|---|---|
| I8D-MC-AZFD | Other Identifier | Eli Lilly and Company | |
| 2016-003440-36 | EudraCT Number |
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As the feeder study (AZES) was stopped for futility after an independent assessment, this trial was also stopped.
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| Name | Class |
|---|---|
| Eli Lilly and Company | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| AZES Lanabecestat 20 milligrams (mg)/AZFD Lanabecestat 20 mg | Experimental | Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. |
|
| AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Experimental | Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. |
|
| AZES Placebo/AZFD Lanabecestat 20 mg | Experimental | Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. |
|
| AZES Placebo/AZFD Lanabecestat 50 mg | Experimental | Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lanabecestat | Drug | Administered orally |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Banner Alzheimer's Institute | Phoenix | Arizona | 85006 | United States | ||
| Territory Neurology & Research Institute |
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| Label | URL |
|---|---|
| Click here for more information about this study: A Study of LY3314814 in Early Alzheimer's Disease Dementia | View source |
| CSP | View source |
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Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Participants who were randomized in Study AZES to either 20 milligrams (mg) or 50 mg of lanabecestat continued on the treatment allocation from the feeder study. Participants randomized to placebo in Study AZES were randomized in a blinded fashion, 1:1 ratio, to either lanabecestat 20 mg or 50 mg daily (QD), administered orally.
Participants who completed feeder study [AZES (NCT02245737)] were enrolled in this study.
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| ID | Title | Description |
|---|---|---|
| FG000 | AZES Placebo/AZFD Lanabecestat 20 mg | Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. |
| FG001 | AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 6, 2018 | Jun 4, 2019 |
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|
| AZES Baseline through AZFD Week 26 |
| 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 |
| 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 |
| 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 |
| 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 |
| Tucson |
| Arizona |
| 85704 |
| United States |
| Pacific Research Network Inc | San Diego | California | 92103 | United States |
| Mile High Research Center | Denver | Colorado | 80218 | United States |
| Institute for Neurodegenerative Disorders | New Haven | Connecticut | 06510 | United States |
| Georgetown University Medical Center | Washington D.C. | District of Columbia | 20057 | United States |
| Brain Matters Research | Delray Beach | Florida | 33445 | United States |
| Compass Research | Orlando | Florida | 32806 | United States |
| IMIC, Inc. | Palmetto Bay | Florida | 33157 | United States |
| Roskamp Institute | Sarasota | Florida | 34243 | United States |
| Suncoast Neuroscience Associates | St. Petersburg | Florida | 33713 | United States |
| Premiere Research Institute at Palm Beach Neurology | West Palm Beach | Florida | 33407 | United States |
| The Multiple Sclerosis Center of Atlanta | Atlanta | Georgia | 30327 | United States |
| University of Chicago Medical Center | Chicago | Illinois | 60637 | United States |
| Community Clinical Research Center | Anderson | Indiana | 46011 | United States |
| Boston Center for Memory | Newton | Massachusetts | 02459 | United States |
| Hattiesburg Clinic | Hattiesburg | Mississippi | 39401 | United States |
| Memory Enhancement Center of America, Inc. | Eatontown | New Jersey | 07724 | United States |
| The Cognitive and Research Center of NJ | Springfield | New Jersey | 07081 | United States |
| Advanced Memory Research Institute of New Jersey | Toms River | New Jersey | 08755 | United States |
| Integrative Clinical Trials, LLC | Brooklyn | New York | 11229 | United States |
| Columbia University Medical Center | New York | New York | 10032 | United States |
| University of Rochester School of Medicine | Rochester | New York | 14620 | United States |
| Valley Medical Primary Care | Centerville | Ohio | 45459 | United States |
| Lindner Research Center | Cincinnati | Ohio | 45219 | United States |
| Ohio State University Medical Center | Columbus | Ohio | 43210 | United States |
| Lehigh Valley Hospital | Allentown | Pennsylvania | 18103 | United States |
| Rhode Island Mood & Memory Research Institute | East Providence | Rhode Island | 02914 | United States |
| Radiant Research | Greer | South Carolina | 29651 | United States |
| Quillen College of Medicine, East TN State University | Johnson City | Tennessee | 37604 | United States |
| The Memory Clinic | Bennington | Vermont | 05201 | United States |
| Southern Neurology | Kogarah | New South Wales | 2217 | Australia |
| Royal Adelaide Hospital | Adelaide | South Australia | 5000 | Australia |
| Eastern Clinical Research Unit | Box Hill | Victoria | 3128 | Australia |
| Delmont Private Hospital | Glen Iris | Victoria | 3146 | Australia |
| The Florey Institute of Neuroscience and Mental Health | Parkville | Victoria | 3052 | Australia |
| Australian Alzheimer's Research Foundation | Nedlands | Western Australia | 6009 | Australia |
| Neuro Trials Victoria Pty Ltd | Noble Park | 3174 | Australia |
| Jessa Ziekenhuis | Hasselt | Limburg | 3500 | Belgium |
| Hopital Universitaire Brugmann Brussel | Brussels | 1020 | Belgium |
| Hospital Universitaire Erasme Brussel | Brussels | 1070 | Belgium |
| Cliniques Universitaires Saint-Luc | Brussels | 1200 | Belgium |
| Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg | Leuven | 3000 | Belgium |
| AZ Delta | Roeselare | 8800 | Belgium |
| Okanagan Clinical Trials | Kelowna | British Columbia | V1Y 1Z9 | Canada |
| True North Clinical Research Halifax, LLC | Halifax | Nova Scotia | B3S1M7 | Canada |
| Elizabeth Bruyere Health Centre | Ottawa | Ontario | KIN 5C8 | Canada |
| Kawartha Regional Memory Clinic | Peterborough | Ontario | K9H2P4 | Canada |
| Toronto Memory Program | Toronto | Ontario | M3B 2S7 | Canada |
| Clinique de la Memoire de l'Outaouais | Gatineau | Quebec | J8T 8J1 | Canada |
| NeuroSearch Developements | Greenfield Park | Quebec | J4V 2J2 | Canada |
| Hopital de L'Enfant Jesus | Québec | Quebec | G1J 1Z4 | Canada |
| Q&T Research Sherbrooke Inc | Sherbrooke | Quebec | J1J 2G2 | Canada |
| Centre Hospitalier Universitaire La Timone | Marseille | Cedex 05 | 13385 | France |
| CHRU de Lille- Hôpital Roger Salengro | Lille | Cedex | 59037 | France |
| CHU de Toulouse Hopital Purpan | Toulouse | Cedex | 31059 | France |
| Hopital Neuro Pierre Wertheimer | Bron | 69677 | France |
| CHU Bocage CMRR | Dijon | 21079 | France |
| Hopital Broca | Paris | 75013 | France |
| Hôpital de la Pitié-Salpêtrière | Paris | 75013 | France |
| Hôpital Fernand Widal | Paris | 75475 | France |
| Chu de Nantes Hopital Laennec | Saint-Herblain | 44093 | France |
| Centre de Recherche Clinique du Gérontopôle Cité de la Santé | Toulouse | 31052 | France |
| Hopital des Charpennes | Villeurbanne | 69100 | France |
| Universitätsklinikum Ulm | Ulm | Baden-Wurttemberg | 89081 | Germany |
| Studien und Gedächtniszentrum München | München | Bavaria | 80331 | Germany |
| Klinikum Rechts der Isar der TU München | München | Bavaria | 81675 | Germany |
| Gemeinschaftspraxis für Neurologie und Psychiatrie | Westerstede | Lower Saxony | 26655 | Germany |
| DataMed Klinische Studien GmbH | Cologne | North Rhine-Westphalia | 50935 | Germany |
| Universitätsklinikum Köln | Cologne | North Rhine-Westphalia | 50937 | Germany |
| Neurologische Praxis Siegen | Siegen | North Rhine-Westphalia | 57076 | Germany |
| Pharm Studienzentrum Chemnitz | Mittweida | Saxony | 09648 | Germany |
| Charité Universitätsmedizin Berlin | Berlin | 10117 | Germany |
| Charité Universitätsmedizin Berlin | Berlin | 12203 | Germany |
| SE Neurologiai Klinika | Budapest | 1083 | Hungary |
| National Institute for Longevity Sciences NCGG | Ōbu | Aichi-ken | 474-0038 | Japan |
| National Chiba-East-Hospital | Chuo-ku | Chiba | 260-8712 | Japan |
| Tsukuba University Hospital | Tsukuba | Ibaraki | 305-8576 | Japan |
| Iwate Medical University Hospital | Morioka | Iwate | 020-8505 | Japan |
| Nihon Kokan Hospital | Kawasaki | Kanagawa | 210-0852 | Japan |
| Katayama Medical Clinic | Kurashiki | Okayama-ken | 701-0192 | Japan |
| Shiroma Clinic | Urasoe | Okinawa | 901-2102 | Japan |
| Sakaguchi Clinic | Sakai | Osaka | 593-8301 | Japan |
| National Sanatorium Toneyama Hospital | Toyonaka | Osaka | 560-8552 | Japan |
| Memory Clinic Ochanomizu | Bunkyo-ku | Tokyo | 113-0034 | Japan |
| Nippon Medical School Hospital | Bunkyo-Ku | Tokyo | 113-8603 | Japan |
| The University of Tokyo Hospital | Bunkyo-ku | Tokyo | 113-8655 | Japan |
| Tokyo Women's Medical University Hospital | Shinjuku-ku | Tokyo | 162-8666 | Japan |
| National Sanatorium Hokuriku Hospital | Nanto | Toyama | 939-1893 | Japan |
| Fukuoka University Hospital | Fukuoka | 814-0180 | Japan |
| Kyoto University Hospital | Kyoto | 606-8507 | Japan |
| Utano Hospital | Kyoto | 616-8255 | Japan |
| Osaka City University Hospital | Osaka | 637086 | Japan |
| Podlaskie Centrum Psychogeriatrii | Bialystok | Podlaskie Voivodeship | 15-732 | Poland |
| NZOZ Dom Sue Ryder - Pallmed Sp. z o.o. | Bydgoszcz | 85-796 | Poland |
| NZOZ Wielospecjalistyczna Poradnia Lekarska | Katowice | 40-123 | Poland |
| Centrum Zdrowia Psychicznego Biomed - Jan Latala | Kielce | 25-411 | Poland |
| Krakowska Akademia Neurologii | Krakow | 31-505 | Poland |
| Medycyna Milorzab | Lodz | 93-118 | Poland |
| Instytut Medycyny Wsi | Lublin | 20-950 | Poland |
| Centrum Medyczne Neuroprotect | Warsaw | 01-697 | Poland |
| Santa Cruz Behavioral PSC | Bayamón | 00961-6911 | Puerto Rico |
| SC Med Life SA | Bucharest | 010719 | Romania |
| SC Centrul Medical Sana SRL | Bucharest | 011025 | Romania |
| Dong-A University Medical Center | Seogu | Busan | 49201 | South Korea |
| Hanyang University Guri Hospital | Guri-si | Gyeonggido | 11923 | South Korea |
| Inha University Hospital | Junggu | Incheon | 22332 | South Korea |
| Samsung Medical Center | Seoul | Korea | 06351 | South Korea |
| Gachon University Gil Medical Center | Incheon | 21565 | South Korea |
| Asan Medical Center | Seoul | 05505 | South Korea |
| Seoul St. Mary's Hospital | Seoul | 06591 | South Korea |
| Hospital General Universitario de Elche | Elche | Alicante | 03203 | Spain |
| Hospital Universitari de Bellvitge | L'Hospitalet de Llobregat | Barcelona | 08907 | Spain |
| Hospital Virgen Del Puerto | Plasencia | Caceres | 10600 | Spain |
| Hospital Universitario De Getafe | Madrid | Getafe | 28905 | Spain |
| CITA Alzheimer | Donostia / San Sebastian | Guipuzcoa | 20009 | Spain |
| Centro de Atencion Especializada (CAE) OROITU | Getxo | Vizcaya | 48993 | Spain |
| Fundacion ACE-Institut Catala de Neurociences Aplicades | Barcelona | 08014 | Spain |
| Hospital Santa Creu I Sant Pau | Barcelona | 08025 | Spain |
| Hospital Clinic I Provincial | Barcelona | 08036 | Spain |
| Hospital De La Princesa | Madrid | 28006 | Spain |
| Hospital Universitario Ramon y Cajal | Madrid | 28034 | Spain |
| Hospital Son Espases | Palma de Mallorca | 07010 | Spain |
| Hospital Universitario Dr Pesset | Valencia | 46017 | Spain |
| Hospital Universitario La Fe de Valencia | Valencia | 46026 | Spain |
| Re-Cognition Health Ltd | London | Greater London | W1G 9JF | United Kingdom |
| MAC Clinical Research-Manchester | Manchester | Greater Manchester | M13 9NQ | United Kingdom |
| MAC Clinical Research | Blackpool | Lancashire | FY2 0JH | United Kingdom |
| West London Mental Health NHS Trust | Isleworth | London | TW7 6FY | United Kingdom |
| MAC Clinical Research | Cannock | Staffordshire | WS11 0BN | United Kingdom |
| Re-Cognition Health Ltd | Guildford | Surrey | GU2 7YD | United Kingdom |
| Glasgow Memory Clinic | Glasgow | G20 0XA | United Kingdom |
| MAC Clinical Research | Leeds | LS10 1DU | United Kingdom |
| SAP | View source |
Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.
| FG002 | AZES Placebo/AZFD Lanabecestat 50 mg | Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. |
| FG003 | AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. |
| Received at Least 1 Dose of Study Drug |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
All randomized participants who received study drug.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | AZES Placebo/AZFD Lanabecestat 20 mg | Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. |
| BG001 | AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg | Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. |
| BG002 | AZES Placebo/AZFD Lanabecestat 50 mg | Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. |
| BG003 | AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. |
| BG004 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Details are from AZES baseline. | Mean | Standard Deviation | Years |
| ||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
| ||||||||||||||||
| ADAS-Cog13 (13-item Alzheimer's Disease Assessment Scale) | ADAS-Cog13, a 13-item rating scale, measured the severity of cognitive dysfunction in persons with Alzheimer's disease (AD). Scores ranged from 0 to 85, with a higher score indicating worse cognitive functioning. Details are from AZES baseline. | Mean | Standard Deviation | Units on a Scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADAS-Cog13 measure. Feeder study AZES was stopped for futility, the original Delayed Start analysis was replaced with MMRM analysis and no comparisons between treatment groups were made. | Posted | Least Squares Mean | Standard Error | Units on a scale | 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. | All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADCS-iADL measure. | Posted | Least Squares Mean | Standard Error | Units on a scale | 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. | All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for FAQ score. | Posted | Least Squares Mean | Standard Error | Units on a scale | 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. | All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for iADRS. | Posted | Least Squares Mean | Standard Error | Units on a scale | 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. | All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for MMSE. | Posted | Least Squares Mean | Standard Error | Units on a scale | 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. | All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for ADAS-Cog13 measure. | Posted | Least Squares Mean | Standard Error | Units on a scale | AZES Baseline through AZFD Week 52 |
|
Up To 156 Weeks
All AZFD participants who received at least one dose of study drug.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | AZES Placebo/AZFD Lanabecestat 20 mg | Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. | 0 | 76 | 3 | 76 | 11 | 76 |
| EG001 | AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg | Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. | 0 | 139 | 8 | 139 | 23 | 139 |
| EG002 | AZES Placebo/AZFD Lanabecestat 50 mg | Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. | 0 | 74 | 5 | 74 | 8 | 74 |
| EG003 | AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. | 1 | 131 | 7 | 131 | 17 | 131 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Bradycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Oesophageal motility disorder | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Small intestinal obstruction | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Femoral neck fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Radiation proctitis | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Electrocardiogram repolarisation abnormality | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 21.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Breast cancer in situ | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
| |
| Breast cancer metastatic | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
| |
| Laryngeal squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Optic neuritis | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Neuropsychiatric symptoms | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
|
This study was stopped after an independent assessment concluded that the feeder study AZES was futile. Because of this, the originally planned delayed-start analysis for this study was not performed.
The sponsor shall review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. Investigator shall delay publication of their results of the study until the results of the multi-center study are published or presented, provided the multi-center results are published within 24 months of the termination.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| AstraZeneca Information Center | AstraZeneca | 877-240-9479 | information.center@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Aug 20, 2018 | Jun 4, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D019636 | Neurodegenerative Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D001523 | Mental Disorders |
| D019965 | Neurocognitive Disorders |
| D024801 | Tauopathies |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| C000608388 | lanabecestat |
Not provided
Not provided
Not provided
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Romania |
|
| Hungary |
|
| United States |
|
| Japan |
|
| United Kingdom |
|
| Spain |
|
| Canada |
|
| South Korea |
|
| Belgium |
|
| Poland |
|
| France |
|
| Australia |
|
| Germany |
|
Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
| OG003 | AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
|
|
Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. |
| OG002 | AZES Placebo/AZFD Lanabecestat 50 mg | Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
| OG003 | AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
|
|
| OG002 |
| AZES Placebo/AZFD Lanabecestat 50 mg |
Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
| OG003 | AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
|
|
Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
| OG003 | AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
|
|
| OG002 | AZES Placebo/AZFD Lanabecestat 50 mg | Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
| OG003 | AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg | Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. |
|
|