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

Sponsor
AstraZeneca (Industry)
Overall Status
Terminated
CT.gov ID
NCT02972658
Collaborator
Eli Lilly and Company (Industry)
421
Enrollment
133
Locations
4
Arms
18.6
Actual Duration (Months)
3.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
421 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
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)
Actual Study Start Date :
Mar 15, 2017
Actual Primary Completion Date :
Oct 2, 2018
Actual Study Completion Date :
Oct 2, 2018

Arms and Interventions

Arm Intervention/Treatment
Experimental: AZES Lanabecestat 20 milligrams (mg)/AZFD Lanabecestat 20 mg

Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.

Drug: Lanabecestat
Administered orally
Other Names:
  • LY3314814
  • AZD3293

    		•
    Experimental: 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.

    Drug: Lanabecestat
    Administered orally
    Other Names:
  • LY3314814
  • AZD3293

    		•
    Experimental: AZES Placebo/AZFD Lanabecestat 20 mg

    Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg.

    Drug: Lanabecestat
    Administered orally
    Other Names:
  • LY3314814
  • AZD3293

    		•
    Experimental: AZES Placebo/AZFD Lanabecestat 50 mg

    Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.

    Drug: Lanabecestat
    Administered orally
    Other Names:
  • LY3314814
  • AZD3293

    		•

    Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    55 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Banner Alzheimer's Institute Phoenix Arizona United States 85006
    2 Territory Neurology & Research Institute Tucson Arizona United States 85704
    3 Pacific Research Network Inc San Diego California United States 92103
    4 Mile High Research Center Denver Colorado United States 80218
    5 Institute for Neurodegenerative Disorders New Haven Connecticut United States 06510
    6 Georgetown University Medical Center Washington District of Columbia United States 20057
    7 Brain Matters Research Delray Beach Florida United States 33445
    8 Compass Research Orlando Florida United States 32806
    9 IMIC, Inc. Palmetto Bay Florida United States 33157
    10 Suncoast Neuroscience Associates Saint Petersburg Florida United States 33713
    11 Roskamp Institute Sarasota Florida United States 34243
    12 Premiere Research Institute at Palm Beach Neurology West Palm Beach Florida United States 33407
    13 The Multiple Sclerosis Center of Atlanta Atlanta Georgia United States 30327
    14 University of Chicago Medical Center Chicago Illinois United States 60637
    15 Community Clinical Research Center Anderson Indiana United States 46011
    16 Boston Center for Memory Newton Massachusetts United States 02459
    17 Hattiesburg Clinic Hattiesburg Mississippi United States 39401
    18 Memory Enhancement Center of America, Inc. Eatontown New Jersey United States 07724
    19 The Cognitive and Research Center of NJ Springfield New Jersey United States 07081
    20 Advanced Memory Research Institute of New Jersey Toms River New Jersey United States 08755
    21 Integrative Clinical Trials, LLC Brooklyn New York United States 11229
    22 Columbia University Medical Center New York New York United States 10032
    23 University of Rochester School of Medicine Rochester New York United States 14620
    24 Valley Medical Primary Care Centerville Ohio United States 45459
    25 Lindner Research Center Cincinnati Ohio United States 45219
    26 Ohio State University Medical Center Columbus Ohio United States 43210
    27 Lehigh Valley Hospital Allentown Pennsylvania United States 18103
    28 Rhode Island Mood & Memory Research Institute East Providence Rhode Island United States 02914
    29 Radiant Research Greer South Carolina United States 29651
    30 Quillen College of Medicine, East TN State University Johnson City Tennessee United States 37604
    31 The Memory Clinic Bennington Vermont United States 05201
    32 Southern Neurology Kogarah New South Wales Australia 2217
    33 Royal Adelaide Hospital Adelaide South Australia Australia 5000
    34 Eastern Clinical Research Unit Box Hill Victoria Australia 3128
    35 Delmont Private Hospital Glen Iris Victoria Australia 3146
    36 The Florey Institute of Neuroscience and Mental Health Parkville Victoria Australia 3052
    37 Australian Alzheimer's Research Foundation Nedlands Western Australia Australia 6009
    38 Neuro Trials Victoria Pty Ltd Noble Park Australia 3174
    39 Jessa Ziekenhuis Hasselt Limburg Belgium 3500
    40 Hopital Universitaire Brugmann Brussel Brussels Belgium 1020
    41 Cliniques Universitaires Saint-Luc Brussels Belgium 1200
    42 Hospital Universitaire Erasme Brussel Brussel Belgium 1070
    43 Universitaire Ziekenhuizen Leuven - Campus Gasthuisberg Leuven Belgium 3000
    44 AZ Delta Roeselare Belgium 8800
    45 Okanagan Clinical Trials Kelowna British Columbia Canada V1Y 1Z9
    46 True North Clinical Research Halifax, LLC Halifax Nova Scotia Canada B3S1M7
    47 Elizabeth Bruyere Health Centre Ottawa Ontario Canada KIN 5C8
    48 Kawartha Regional Memory Clinic Peterborough Ontario Canada K9H2P4
    49 Toronto Memory Program Toronto Ontario Canada M3B 2S7
    50 Clinique de la Memoire de l'Outaouais Gatineau Quebec Canada J8T 8J1
    51 NeuroSearch Developements Greenfield Park Quebec Canada J4V 2J2
    52 Hopital de L'Enfant Jesus Quebec City Quebec Canada G1J 1Z4
    53 Q&T Research Sherbrooke Inc Sherbrooke Quebec Canada J1J 2G2
    54 Centre Hospitalier Universitaire La Timone Marseille Cedex 05 France 13385
    55 CHRU de Lille- Hôpital Roger Salengro Lille Cedex France 59037
    56 CHU de Toulouse Hopital Purpan Toulouse Cedex France 31059
    57 Hopital Neuro Pierre Wertheimer Bron Cedex France 69677
    58 CHU Bocage CMRR Dijon France 21079
    59 Hopital Broca Paris France 75013
    60 Hôpital de la Pitié-Salpêtrière Paris France 75013
    61 Hôpital Fernand Widal Paris France 75475
    62 Chu de Nantes Hopital Laennec Saint-Herblain France 44093
    63 Centre de Recherche Clinique du Gérontopôle Cité de la Santé Toulouse France 31052
    64 Hopital des Charpennes Villeurbanne France 69100
    65 Universitätsklinikum Ulm Ulm Baden-Württemberg Germany 89081
    66 Studien und Gedächtniszentrum München München Bayern Germany 80331
    67 Klinikum Rechts der Isar der TU München München Bayern Germany 81675
    68 Gemeinschaftspraxis für Neurologie und Psychiatrie Westerstede Niedersachsen Germany 26655
    69 DataMed Klinische Studien GmbH Köln Nordrhein-Westfalen Germany 50935
    70 Universitätsklinikum Köln Köln Nordrhein-Westfalen Germany 50937
    71 Neurologische Praxis Siegen Siegen Nordrhein-Westfalen Germany 57076
    72 Pharm Studienzentrum Chemnitz Mittweida Sachsen Germany 09648
    73 Charité Universitätsmedizin Berlin Berlin Germany 10117
    74 Charité Universitätsmedizin Berlin Berlin Germany 12203
    75 SE Neurologiai Klinika Budapest Hungary 1083
    76 National Institute for Longevity Sciences NCGG Obu Aichi Japan 474-0038
    77 National Chiba-East-Hospital Chuo-ku Chiba Japan 260-8712
    78 Tsukuba University Hospital Tsukuba Ibaraki Japan 305-8576
    79 Iwate Medical University Hospital Morioka Iwate Japan 020-8505
    80 Nihon Kokan Hospital Kawasaki Kanagawa Japan 210-0852
    81 Katayama Medical Clinic Kurashiki Okayama Japan 701-0192
    82 Shiroma Clinic Urasoe Okinawa Japan 901-2102
    83 Sakaguchi Clinic Sakai Osaka Japan 593-8301
    84 National Sanatorium Toneyama Hospital Toyonaka Osaka Japan 560-8552
    85 Memory Clinic Ochanomizu Bunkyo-ku Tokyo Japan 113-0034
    86 Nippon Medical School Hospital Bunkyo-Ku Tokyo Japan 113-8603
    87 The University of Tokyo Hospital Bunkyo-ku Tokyo Japan 113-8655
    88 Tokyo Women's Medical University Hospital Shinjuku-ku Tokyo Japan 162-8666
    89 National Sanatorium Hokuriku Hospital Nanto Toyama Japan 939-1893
    90 Fukuoka University Hospital Fukuoka Japan 814-0180
    91 Kyoto University Hospital Kyoto Japan 606-8507
    92 Utano Hospital Kyoto Japan 616-8255
    93 Osaka City University Hospital Osaka Japan 637086
    94 Dong-A University Medical Center Seogu Busan Korea, Republic of 49201
    95 Hanyang University Guri Hospital Guri-si Gyeonggido Korea, Republic of 11923
    96 Inha University Hospital Junggu Incheon Korea, Republic of 22332
    97 Samsung Medical Center Seoul Korea Korea, Republic of 06351
    98 Gachon University Gil Medical Center Incheon Korea, Republic of 21565
    99 Asan Medical Center Seoul Korea, Republic of 05505
    100 Seoul St. Mary's Hospital Seoul Korea, Republic of 06591
    101 Podlaskie Centrum Psychogeriatrii Białystok Podlaskie Poland 15-732
    102 NZOZ Dom Sue Ryder - Pallmed Sp. z o.o. Bydgoszcz Poland 85-796
    103 NZOZ Wielospecjalistyczna Poradnia Lekarska Katowice Poland 40-123
    104 Centrum Zdrowia Psychicznego Biomed - Jan Latala Kielce Poland 25-411
    105 Krakowska Akademia Neurologii Krakow Poland 31-505
    106 Medycyna Milorzab Lodz Poland 93-118
    107 Instytut Medycyny Wsi Lublin Poland 20-950
    108 Centrum Medyczne Neuroprotect Warszawa Poland 01-697
    109 Santa Cruz Behavioral PSC Bayamón Puerto Rico 00961-6911
    110 SC Med Life SA Bucuresti Romania 010719
    111 SC Centrul Medical Sana SRL Bucuresti Romania 011025
    112 Hospital General Universitario de Elche Elche Alicante Spain 03203
    113 Hospital Universitari de Bellvitge Hospitalet de Llobregat Barcelona Spain 08907
    114 Hospital Virgen Del Puerto Plasencia Caceres Spain 10600
    115 Hospital Universitario De Getafe Madrid Getafe Spain 28905
    116 CITA Alzheimer San Sebastian Guipuzcoa Spain 20009
    117 Centro de Atencion Especializada (CAE) OROITU Getxo Vizcaya Spain 48993
    118 Fundacion ACE-Institut Catala de Neurociences Aplicades Barcelona Spain 08014
    119 Hospital Santa Creu I Sant Pau Barcelona Spain 08025
    120 Hospital Clinic I Provincial Barcelona Spain 08036
    121 Hospital De La Princesa Madrid Spain 28006
    122 Hospital Universitario Ramon y Cajal Madrid Spain 28034
    123 Hospital Son Espases Palma De Mallorca Spain 07010
    124 Hospital Universitario Dr Pesset Valencia Spain 46017
    125 Hospital Universitario La Fe de Valencia Valencia Spain 46026
    126 Re-Cognition Health Ltd London Greater London United Kingdom W1G 9JF
    127 MAC Clinical Research-Manchester Manchester Greater Manchester United Kingdom M13 9NQ
    128 MAC Clinical Research Blackpool Lancashire United Kingdom FY2 0JH
    129 West London Mental Health NHS Trust Isleworth London United Kingdom TW7 6FY
    130 MAC Clinical Research Cannock Staffordshire United Kingdom WS11 0BN
    131 Re-Cognition Health Ltd Guildford Surrey United Kingdom GU2 7YD
    132 Glasgow Memory Clinic Glasgow United Kingdom G20 0XA
    133 MAC Clinical Research Leeds United Kingdom LS10 1DU

    Sponsors and Collaborators

    • AstraZeneca
    • Eli Lilly and Company

    Investigators

    • Study Director: 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 Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02972658
    Other Study ID Numbers:
    • 16557
    • I8D-MC-AZFD
    • 2016-003440-36
    First Posted:
    Nov 23, 2016
    Last Update Posted:
    Dec 3, 2019
    Last Verified:
    Nov 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AstraZeneca
    Alzheimer's Disease
    Dementia
    Brain Diseases
    Neurodegenerative Diseases
    Central Nervous System Diseases
    Nervous System Diseases
    Mental Disorders
    Delirium, Dementia, Amnestic, Cognitive Disorders
    Tauopathies
    Memory
    Amyloid
    Additional relevant MeSH terms:
    Alzheimer Disease
    Dementia

    Study Results

    Participant Flow

    Recruitment Details Participants who completed feeder study [AZES (NCT02245737)] were enrolled in this study.
    Pre-assignment Detail 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.
    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Arm/Group Description Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg.
    Period Title: Overall Study
    STARTED 76 139 75 131
    Received at Least 1 Dose of Study Drug 76 139 74 131
    COMPLETED 0 1 0 0
    NOT COMPLETED 76 138 75 131

    Baseline Characteristics

    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg Total
    Arm/Group Description Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. Participants who received Lanabecestat 20 mg in the feeder study (AZES) were randomized to receive Lanabecestat 20 mg. Participants who received placebo in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. Participants who received Lanabecestat 50 mg in the feeder study (AZES) were randomized to receive Lanabecestat 50 mg. Total of all reporting groups
    Overall Participants 76 139 75 131 421
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    70.7
    (6.6)
    69.8
    (7.8)
    71.1
    (6.6)
    70.1
    (6.7)
    70.3
    (7.0)
    Sex: Female, Male (Count of Participants)
    Female
    35
    46.1%
    76
    54.7%
    40
    53.3%
    75
    57.3%
    226
    53.7%
    Male
    41
    53.9%
    63
    45.3%
    35
    46.7%
    56
    42.7%
    195
    46.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    7
    9.2%
    4
    2.9%
    4
    5.3%
    3
    2.3%
    18
    4.3%
    Not Hispanic or Latino
    62
    81.6%
    115
    82.7%
    54
    72%
    114
    87%
    345
    81.9%
    Unknown or Not Reported
    7
    9.2%
    20
    14.4%
    17
    22.7%
    14
    10.7%
    58
    13.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    7
    9.2%
    23
    16.5%
    10
    13.3%
    16
    12.2%
    56
    13.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    2
    1.4%
    1
    1.3%
    0
    0%
    3
    0.7%
    White
    64
    84.2%
    104
    74.8%
    51
    68%
    106
    80.9%
    325
    77.2%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    5
    6.6%
    10
    7.2%
    13
    17.3%
    9
    6.9%
    37
    8.8%
    Region of Enrollment (Count of Participants)
    Puerto Rico
    0
    0%
    1
    0.7%
    0
    0%
    0
    0%
    1
    0.2%
    Romania
    1
    1.3%
    1
    0.7%
    0
    0%
    0
    0%
    2
    0.5%
    Hungary
    1
    1.3%
    0
    0%
    0
    0%
    0
    0%
    1
    0.2%
    United States
    23
    30.3%
    35
    25.2%
    13
    17.3%
    23
    17.6%
    94
    22.3%
    Japan
    6
    7.9%
    14
    10.1%
    5
    6.7%
    14
    10.7%
    39
    9.3%
    United Kingdom
    8
    10.5%
    17
    12.2%
    8
    10.7%
    13
    9.9%
    46
    10.9%
    Spain
    10
    13.2%
    21
    15.1%
    8
    10.7%
    21
    16%
    60
    14.3%
    Canada
    6
    7.9%
    8
    5.8%
    5
    6.7%
    14
    10.7%
    33
    7.8%
    South Korea
    1
    1.3%
    7
    5%
    3
    4%
    2
    1.5%
    13
    3.1%
    Belgium
    5
    6.6%
    2
    1.4%
    0
    0%
    4
    3.1%
    11
    2.6%
    Poland
    6
    7.9%
    8
    5.8%
    6
    8%
    14
    10.7%
    34
    8.1%
    France
    4
    5.3%
    9
    6.5%
    12
    16%
    8
    6.1%
    33
    7.8%
    Australia
    3
    3.9%
    13
    9.4%
    8
    10.7%
    6
    4.6%
    30
    7.1%
    Germany
    2
    2.6%
    3
    2.2%
    7
    9.3%
    12
    9.2%
    24
    5.7%
    ADAS-Cog13 (13-item Alzheimer's Disease Assessment Scale) (Units on a Scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Units on a Scale]
    27.9
    (8.3)
    29.6
    (7.8)
    27.0
    (7.5)
    27.1
    (7.5)
    27.9
    (7.8)

    Outcome Measures

    1. Primary Outcome
    Title Change From Baseline Analysis on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)
    Description 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.
    Time Frame AZES Baseline through AZFD Week 26

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Arm/Group Description Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
    Measure Participants 76 139 75 131
    Least Squares Mean (Standard Error) [Units on a scale]
    9.61
    (1.60)
    9.25
    (1.21)
    8.41
    (1.65)
    10.41
    (1.25)
    2. Secondary Outcome
    Title Change From Baseline Analysis on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL)
    Description 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.
    Time Frame AZES Baseline through AZFD Week 26

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Arm/Group Description Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
    Measure Participants 76 139 74 129
    Least Squares Mean (Standard Error) [Units on a scale]
    -9.19
    (1.47)
    -8.45
    (1.10)
    -7.37
    (1.51)
    -7.48
    (1.14)
    3. Secondary Outcome
    Title Change From Baseline on the Functional Activities Questionnaire (FAQ) Score
    Description 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.
    Time Frame AZES Baseline through AZFD Week 26

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Arm/Group Description Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
    Measure Participants 76 137 74 130
    Least Squares Mean (Standard Error) [Units on a scale]
    6.28
    (0.98)
    7.09
    (0.76)
    6.73
    (1.01)
    6.91
    (0.79)
    4. Secondary Outcome
    Title Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score
    Description 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.
    Time Frame AZES Baseline through AZFD Week 26

    Outcome Measure Data

    Analysis Population Description
    All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for iADRS.
    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Arm/Group Description Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
    Measure Participants 76 138 72 123
    Least Squares Mean (Standard Error) [Units on a scale]
    -18.85
    (2.58)
    -17.57
    (1.97)
    -15.37
    (2.76)
    -18.37
    (2.09)
    5. Secondary Outcome
    Title Change From Baseline on the Mini-Mental Status Examination (MMSE)
    Description 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.
    Time Frame AZES Baseline through AZFD Week 26

    Outcome Measure Data

    Analysis Population Description
    All AZFD participants who received at least one dose of study drug and have baseline and at least one post-baseline data for MMSE.
    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Arm/Group Description Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
    Measure Participants 76 139 75 131
    Least Squares Mean (Standard Error) [Units on a scale]
    -5.84
    (0.71)
    -5.73
    (0.54)
    -4.72
    (0.72)
    -5.25
    (0.56)
    6. Secondary Outcome
    Title Change From Baseline Analysis on the ADAS-Cog13
    Description 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.
    Time Frame AZES Baseline through AZFD Week 52

    Outcome Measure Data

    Analysis Population Description
    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.
    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Arm/Group Description Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
    Measure Participants 76 139 75 131
    Least Squares Mean (Standard Error) [Units on a scale]
    16.64
    (3.45)
    12.40
    (2.25)
    16.79
    (2.47)
    15.05
    (2.06)

    Adverse Events

    Time Frame Up To 156 Weeks
    Adverse Event Reporting Description All AZFD participants who received at least one dose of study drug.
    Arm/Group Title AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Arm/Group Description Participants who received placebo in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received Lanabecestat 20 mg in the feeder study (AZES) received Lanabecestat 20 mg in AZFD. Participants who received placebo in the feeder study (AZES) received Lanabecestat 50 mg in AZFD. Participants who received Lanabecestat 50 mg in the feeder study (AZES) received Lanabecestat 50 mg in AZFD.
    All Cause Mortality
    AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/76 (0%) 0/139 (0%) 0/74 (0%) 1/131 (0.8%)
    Serious Adverse Events
    AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/76 (3.9%) 8/139 (5.8%) 5/74 (6.8%) 7/131 (5.3%)
    Cardiac disorders
    Bradycardia 0/76 (0%) 0 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Gastrointestinal disorders
    Colitis 0/76 (0%) 0 1/139 (0.7%) 1 0/74 (0%) 0 0/131 (0%) 0
    Enteritis 0/76 (0%) 0 1/139 (0.7%) 1 0/74 (0%) 0 0/131 (0%) 0
    Oesophageal motility disorder 0/76 (0%) 0 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Small intestinal obstruction 0/76 (0%) 0 0/139 (0%) 0 1/74 (1.4%) 1 0/131 (0%) 0
    Infections and infestations
    Diverticulitis 0/76 (0%) 0 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Influenza 0/76 (0%) 0 0/139 (0%) 0 1/74 (1.4%) 1 0/131 (0%) 0
    Pneumonia 0/76 (0%) 0 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Injury, poisoning and procedural complications
    Fall 1/76 (1.3%) 1 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Femoral neck fracture 1/76 (1.3%) 1 1/139 (0.7%) 1 0/74 (0%) 0 0/131 (0%) 0
    Femur fracture 0/76 (0%) 0 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Radiation proctitis 0/76 (0%) 0 0/139 (0%) 0 1/74 (1.4%) 1 0/131 (0%) 0
    Investigations
    Electrocardiogram repolarisation abnormality 0/76 (0%) 0 0/139 (0%) 0 1/74 (1.4%) 1 0/131 (0%) 0
    Weight decreased 0/76 (0%) 0 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Musculoskeletal and connective tissue disorders
    Back pain 0/76 (0%) 0 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Musculoskeletal chest pain 0/76 (0%) 0 0/139 (0%) 0 0/74 (0%) 0 1/131 (0.8%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer in situ 0/76 (0%) 0 1/139 (0.7%) 1 0/74 (0%) 0 0/131 (0%) 0
    Breast cancer metastatic 0/76 (0%) 0 1/139 (0.7%) 1 0/74 (0%) 0 0/131 (0%) 0
    Laryngeal squamous cell carcinoma 1/76 (1.3%) 1 0/139 (0%) 0 0/74 (0%) 0 0/131 (0%) 0
    Nervous system disorders
    Ischaemic stroke 0/76 (0%) 0 1/139 (0.7%) 1 0/74 (0%) 0 0/131 (0%) 0
    Optic neuritis 0/76 (0%) 0 1/139 (0.7%) 1 0/74 (0%) 0 0/131 (0%) 0
    Psychiatric disorders
    Depression 0/76 (0%) 0 1/139 (0.7%) 1 0/74 (0%) 0 0/131 (0%) 0
    Neuropsychiatric symptoms 0/76 (0%) 0 0/139 (0%) 0 1/74 (1.4%) 1 1/131 (0.8%) 1
    Other (Not Including Serious) Adverse Events
    AZES Placebo/AZFD Lanabecestat 20 mg AZES Lanabecestat 20 mg/AZFD Lanabecestat 20 mg AZES Placebo/AZFD Lanabecestat 50 mg AZES Lanabecestat 50 mg/AZFD Lanabecestat 50 mg
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/76 (14.5%) 23/139 (16.5%) 8/74 (10.8%) 17/131 (13%)
    Gastrointestinal disorders
    Diarrhoea 2/76 (2.6%) 2 8/139 (5.8%) 8 2/74 (2.7%) 2 6/131 (4.6%) 6
    Infections and infestations
    Nasopharyngitis 1/76 (1.3%) 1 8/139 (5.8%) 10 3/74 (4.1%) 3 5/131 (3.8%) 7
    Injury, poisoning and procedural complications
    Fall 4/76 (5.3%) 4 7/139 (5%) 8 3/74 (4.1%) 3 5/131 (3.8%) 8
    Psychiatric disorders
    Depression 4/76 (5.3%) 4 3/139 (2.2%) 3 0/74 (0%) 0 2/131 (1.5%) 2

    Limitations/Caveats

    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.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    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.

    Results Point of Contact

    Name/Title AstraZeneca Information Center
    Organization AstraZeneca
    Phone 877-240-9479
    Email information.center@astrazeneca.com
    Responsible Party:
    AstraZeneca
    ClinicalTrials.gov Identifier:
    NCT02972658
    Other Study ID Numbers:
    • 16557
    • I8D-MC-AZFD
    • 2016-003440-36
    First Posted:
    Nov 23, 2016
    Last Update Posted:
    Dec 3, 2019
    Last Verified:
    Nov 1, 2019