Trial Review

Did you know?

The ANZCTR now automatically displays published trial results and simplifies the addition of trial documents such as unpublished protocols and statistical analysis plans.

These enhancements will offer a more comprehensive view of trials, regardless of whether their results are positive, negative, or inconclusive.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02245737




Registration number
NCT02245737
Ethics application status
Date submitted
18/09/2014
Date registered
22/09/2014
Date last updated
3/12/2019

Titles & IDs
Public title
An Efficacy and Safety Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease
Scientific title
A 24-month, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group, Efficacy, Safety, Tolerability, Biomarker, and Pharmacokinetic Study of AZD3293 in Early Alzheimer's Disease (The AMARANTH Study)
Secondary ID [1] 0 0
I8D-MC-AZES
Secondary ID [2] 0 0
16023
Universal Trial Number (UTN)
Trial acronym
AMARANTH
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Alzheimer´s Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Lanabecestat
Treatment: Drugs - Placebo

Experimental: Lanabecestat 20 milligrams (mg) - Lanabecestat 20 mg given orally once daily for 104 weeks.

Experimental: Lanabecestat 50 mg - Lanabecestat 50 mg given orally once daily for 104 weeks.

Placebo comparator: Placebo - Placebo given orally once daily for 104 weeks.


Treatment: Drugs: Lanabecestat
Administered orally

Treatment: Drugs: Placebo
Administered orally
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)
Timepoint [1] 0 0
Baseline, Week 104
Secondary outcome [1] 0 0
Change From Baseline on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL)
Timepoint [1] 0 0
Baseline, Week 104
Secondary outcome [2] 0 0
Change From Baseline on the Functional Activities Questionnaire (FAQ) Score
Timepoint [2] 0 0
Baseline, Week 104
Secondary outcome [3] 0 0
Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score
Timepoint [3] 0 0
Baseline, Week 104
Secondary outcome [4] 0 0
Change From Baseline on the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score
Timepoint [4] 0 0
Baseline, Week 104
Secondary outcome [5] 0 0
Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage
Timepoint [5] 0 0
Baseline through Loss of 1 Global Stage or Week 104
Secondary outcome [6] 0 0
Change From Baseline in Neuropsychiatric Inventory (NPI) Score
Timepoint [6] 0 0
Baseline, Week 104
Secondary outcome [7] 0 0
Change From Baseline on the Mini-Mental State Examination (MMSE)
Timepoint [7] 0 0
Baseline, Week 104
Secondary outcome [8] 0 0
Pharmacodynamics (PD): Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aß)1-42
Timepoint [8] 0 0
Baseline, Week 97
Secondary outcome [9] 0 0
PD: Percent Change From Baseline in Concentration of CSF Biomarker Aß1-40
Timepoint [9] 0 0
Baseline, Week 97
Secondary outcome [10] 0 0
Change From Baseline in CSF Total Tau
Timepoint [10] 0 0
Baseline, Week 97
Secondary outcome [11] 0 0
Change From Baseline in CSF Phosphorylated Tau
Timepoint [11] 0 0
Baseline, Week 97
Secondary outcome [12] 0 0
Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan
Timepoint [12] 0 0
Baseline, Week 104
Secondary outcome [13] 0 0
Change From Baseline in Tau PET ((Flortaucipir F18)
Timepoint [13] 0 0
Baseline, Week 104
Secondary outcome [14] 0 0
Change From Baseline in Brain Metabolism Using Fluorodeoxyglucose (FDG)
Timepoint [14] 0 0
Baseline, Week 104
Secondary outcome [15] 0 0
Change From Baseline in Whole Brain Volume
Timepoint [15] 0 0
Baseline, Week 104
Secondary outcome [16] 0 0
Pharmacokinetics (PK): Plasma Concentration of Lanabecestat
Timepoint [16] 0 0
Week 4, post dose prior to departure from the clinic

Eligibility
Key inclusion criteria
* Gradual and progressive change in the participant's memory function over more than 6 months, reported by participant and study partner
* Mini-Mental State Examination score of 20-30 inclusive at screening
* Objective impairment in memory as evaluated by memory test performed at screening
* For a diagnosis of mild Alzheimer's Disease (AD), participant meets the National Institute on Aging and the Alzheimer's Association (NIA-AA) criteria for probable AD
* For a diagnosis of MCI due to AD, participant meets NIA-AA criteria for MCI due to AD
Minimum age
55 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Significant neurological disease affecting the central nervous system, other than AD, that may affect cognition or ability to complete the study, including but not limited to, other dementias, serious infection of the brain, Parkinson´s disease, or epilepsy or recurrent seizures
* History of clinically evident stroke, or multiple strokes based on history or imaging results
* History of clinically important carotid or vertebrobasilar stenosis or plaque
* History of multiple concussions with sustained cognitive complaints or objective change in neuropsychological function in the last 5 years
* Participants with a current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition diagnosis of Major Depressive Disorder or any current primary psychiatric diagnosis other than AD if, in the judgment of the investigator, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessments, or affect the participant´s ability to complete the study
* History of alcohol or drug abuse or dependence (except nicotine dependence) within 2 years before the screening
* Within 1 year before the screening or between screening and baseline, any of the following: myocardial infarction; moderate or severe congestive heart failure, New York Heart Association class III or IV; hospitalization for, or symptom of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease (eg, significant valvular disease, hypertrophic cardiomyopathy), or hospitalization for arrhythmia
* Congenital QT prolongation
* History of cancer within the last 5 years, with the exception of non-metastatic basal and/or squamous cell carcinoma of the skin, in situ cervical cancer, non-progressive prostate cancer or other cancers with low-risk of recurrence or spread
* Current serious or unstable clinically important systemic illness that, in the judgment of the investigator, is likely to affect cognitive assessment, deteriorate, or affect the participant's safety or ability to complete the study, including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, or hematologic disorders

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
30/09/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/10/2018
Sample size
Target
Accrual to date
Final
2218
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Southern Neurology - Kogarah
Recruitment hospital [2] 0 0
Griffith University - Gold Coast
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Box Hill Hospital - Box Hill
Recruitment hospital [5] 0 0
Delmont Private Hospital - Glen Iris
Recruitment hospital [6] 0 0
Heidelberg Repatriation Hospital - Heidelberg
Recruitment hospital [7] 0 0
The Florey Institute of Neuroscience and Mental Health - Parkville
Recruitment hospital [8] 0 0
Australian Alzheimer's Research Foundation - Nedlands
Recruitment hospital [9] 0 0
Neuro Trials Victoria Pty Ltd - Noble Park
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
4222 - Gold Coast
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
3146 - Glen Iris
Recruitment postcode(s) [6] 0 0
3081 - Heidelberg
Recruitment postcode(s) [7] 0 0
3052 - Parkville
Recruitment postcode(s) [8] 0 0
6009 - Nedlands
Recruitment postcode(s) [9] 0 0
3174 - Noble Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
Country [5] 0 0
United States of America
State/province [5] 0 0
District of Columbia
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Mississippi
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
New Jersey
Country [14] 0 0
United States of America
State/province [14] 0 0
New York
Country [15] 0 0
United States of America
State/province [15] 0 0
North Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Ohio
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
Rhode Island
Country [20] 0 0
United States of America
State/province [20] 0 0
South Carolina
Country [21] 0 0
United States of America
State/province [21] 0 0
Tennessee
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Utah
Country [24] 0 0
United States of America
State/province [24] 0 0
Vermont
Country [25] 0 0
Belgium
State/province [25] 0 0
Limburg
Country [26] 0 0
Belgium
State/province [26] 0 0
Brussels
Country [27] 0 0
Belgium
State/province [27] 0 0
Brussel
Country [28] 0 0
Belgium
State/province [28] 0 0
Edegem
Country [29] 0 0
Belgium
State/province [29] 0 0
Leuven
Country [30] 0 0
Belgium
State/province [30] 0 0
Roeselare
Country [31] 0 0
Canada
State/province [31] 0 0
British Columbia
Country [32] 0 0
Canada
State/province [32] 0 0
Nova Scotia
Country [33] 0 0
Canada
State/province [33] 0 0
Ontario
Country [34] 0 0
Canada
State/province [34] 0 0
Qubec
Country [35] 0 0
Canada
State/province [35] 0 0
Quebec
Country [36] 0 0
France
State/province [36] 0 0
Cedex 9
Country [37] 0 0
France
State/province [37] 0 0
Bron Cedex
Country [38] 0 0
France
State/province [38] 0 0
Dijon Cedex
Country [39] 0 0
France
State/province [39] 0 0
Lille Cedex
Country [40] 0 0
France
State/province [40] 0 0
Marseille Cedex 05
Country [41] 0 0
France
State/province [41] 0 0
Nantes
Country [42] 0 0
France
State/province [42] 0 0
Paris
Country [43] 0 0
France
State/province [43] 0 0
Toulouse
Country [44] 0 0
France
State/province [44] 0 0
Villeurbanne
Country [45] 0 0
Germany
State/province [45] 0 0
Baden-Württemberg
Country [46] 0 0
Germany
State/province [46] 0 0
Bayern
Country [47] 0 0
Germany
State/province [47] 0 0
Niedersachsen
Country [48] 0 0
Germany
State/province [48] 0 0
Nordrhein-Westfalen
Country [49] 0 0
Germany
State/province [49] 0 0
Saarland
Country [50] 0 0
Germany
State/province [50] 0 0
Sachsen-Anhalt
Country [51] 0 0
Germany
State/province [51] 0 0
Sachsen
Country [52] 0 0
Germany
State/province [52] 0 0
Thüringen
Country [53] 0 0
Germany
State/province [53] 0 0
Berlin
Country [54] 0 0
Hungary
State/province [54] 0 0
Baranya
Country [55] 0 0
Hungary
State/province [55] 0 0
Budapest
Country [56] 0 0
Hungary
State/province [56] 0 0
Debrecen
Country [57] 0 0
Hungary
State/province [57] 0 0
Szeged
Country [58] 0 0
Italy
State/province [58] 0 0
Biella
Country [59] 0 0
Italy
State/province [59] 0 0
Milano
Country [60] 0 0
Italy
State/province [60] 0 0
Palermo
Country [61] 0 0
Italy
State/province [61] 0 0
PI
Country [62] 0 0
Italy
State/province [62] 0 0
Ancona
Country [63] 0 0
Italy
State/province [63] 0 0
Brescia
Country [64] 0 0
Italy
State/province [64] 0 0
Chieti
Country [65] 0 0
Italy
State/province [65] 0 0
Genova
Country [66] 0 0
Italy
State/province [66] 0 0
Modena
Country [67] 0 0
Italy
State/province [67] 0 0
Roma
Country [68] 0 0
Italy
State/province [68] 0 0
Torino
Country [69] 0 0
Japan
State/province [69] 0 0
Aichi
Country [70] 0 0
Japan
State/province [70] 0 0
Chiba
Country [71] 0 0
Japan
State/province [71] 0 0
Hokkaido
Country [72] 0 0
Japan
State/province [72] 0 0
Ibaraki
Country [73] 0 0
Japan
State/province [73] 0 0
Iwate
Country [74] 0 0
Japan
State/province [74] 0 0
Kanagawa
Country [75] 0 0
Japan
State/province [75] 0 0
Kyoto
Country [76] 0 0
Japan
State/province [76] 0 0
Nagano
Country [77] 0 0
Japan
State/province [77] 0 0
Okayama
Country [78] 0 0
Japan
State/province [78] 0 0
Okinawa
Country [79] 0 0
Japan
State/province [79] 0 0
Osaka
Country [80] 0 0
Japan
State/province [80] 0 0
Saitama
Country [81] 0 0
Japan
State/province [81] 0 0
Tokyo
Country [82] 0 0
Japan
State/province [82] 0 0
Toyama
Country [83] 0 0
Japan
State/province [83] 0 0
Fukuoka
Country [84] 0 0
Korea, Republic of
State/province [84] 0 0
Busan
Country [85] 0 0
Korea, Republic of
State/province [85] 0 0
Geonggi-do
Country [86] 0 0
Korea, Republic of
State/province [86] 0 0
Gyeonggi-do
Country [87] 0 0
Korea, Republic of
State/province [87] 0 0
Gyeonggido
Country [88] 0 0
Korea, Republic of
State/province [88] 0 0
Incheon
Country [89] 0 0
Korea, Republic of
State/province [89] 0 0
Seoul
Country [90] 0 0
Poland
State/province [90] 0 0
Dolnoslaskie
Country [91] 0 0
Poland
State/province [91] 0 0
Lódzkie
Country [92] 0 0
Poland
State/province [92] 0 0
Podlaskie
Country [93] 0 0
Poland
State/province [93] 0 0
Bydgoszcz
Country [94] 0 0
Poland
State/province [94] 0 0
Katowice
Country [95] 0 0
Poland
State/province [95] 0 0
Kielce
Country [96] 0 0
Poland
State/province [96] 0 0
Krakow
Country [97] 0 0
Poland
State/province [97] 0 0
Lublin
Country [98] 0 0
Poland
State/province [98] 0 0
Siemianowice Slaskie
Country [99] 0 0
Poland
State/province [99] 0 0
Warszawa
Country [100] 0 0
Puerto Rico
State/province [100] 0 0
Bayamon
Country [101] 0 0
Puerto Rico
State/province [101] 0 0
Carolina
Country [102] 0 0
Puerto Rico
State/province [102] 0 0
San Juan
Country [103] 0 0
Romania
State/province [103] 0 0
Bucuresti
Country [104] 0 0
Romania
State/province [104] 0 0
Timisoara
Country [105] 0 0
Spain
State/province [105] 0 0
Alicante
Country [106] 0 0
Spain
State/province [106] 0 0
Barcelona
Country [107] 0 0
Spain
State/province [107] 0 0
Caceres
Country [108] 0 0
Spain
State/province [108] 0 0
Getafe
Country [109] 0 0
Spain
State/province [109] 0 0
Madrid
Country [110] 0 0
Spain
State/province [110] 0 0
Vizcaya
Country [111] 0 0
Spain
State/province [111] 0 0
Cordoba
Country [112] 0 0
Spain
State/province [112] 0 0
Palma de Mallorca
Country [113] 0 0
Spain
State/province [113] 0 0
Reus
Country [114] 0 0
Spain
State/province [114] 0 0
San Sebastian
Country [115] 0 0
Spain
State/province [115] 0 0
Valencia
Country [116] 0 0
United Kingdom
State/province [116] 0 0
Devon
Country [117] 0 0
United Kingdom
State/province [117] 0 0
East Sussex
Country [118] 0 0
United Kingdom
State/province [118] 0 0
Hampshire
Country [119] 0 0
United Kingdom
State/province [119] 0 0
Lancs
Country [120] 0 0
United Kingdom
State/province [120] 0 0
Leeds
Country [121] 0 0
United Kingdom
State/province [121] 0 0
Staffordshire
Country [122] 0 0
United Kingdom
State/province [122] 0 0
Brentford
Country [123] 0 0
United Kingdom
State/province [123] 0 0
Glasgow
Country [124] 0 0
United Kingdom
State/province [124] 0 0
London
Country [125] 0 0
United Kingdom
State/province [125] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to assess the efficacy and safety of lanabecestat compared with placebo administered for 104 weeks in the treatment of early Alzheimer´s disease. The study will test the hypothesis that lanabecestat is a disease-modifying treatment for participants with early Alzheimer´s disease, defined as the continuum of participants with mild cognitive impairment (MCI) due to Alzheimer´s disease and participants diagnosed with mild dementia of the Alzheimer´s type, as measured by change from baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) score at week 104 in each of the 2 lanabecestat treatment groups compared with placebo.
Trial website
https://clinicaltrials.gov/study/NCT02245737
Trial related presentations / publications
Wessels AM, Lines C, Stern RA, Kost J, Voss T, Mozley LH, Furtek C, Mukai Y, Aisen PS, Cummings JL, Tariot PN, Vellas B, Dupre N, Randolph C, Michelson D, Andersen SW, Shering C, Sims JR, Egan MF. Cognitive outcomes in trials of two BACE inhibitors in Alzheimer's disease. Alzheimers Dement. 2020 Nov;16(11):1483-1492. doi: 10.1002/alz.12164. Epub 2020 Oct 13.
Wessels AM, Tariot PN, Zimmer JA, Selzler KJ, Bragg SM, Andersen SW, Landry J, Krull JH, Downing AM, Willis BA, Shcherbinin S, Mullen J, Barker P, Schumi J, Shering C, Matthews BR, Stern RA, Vellas B, Cohen S, MacSweeney E, Boada M, Sims JR. Efficacy and Safety of Lanabecestat for Treatment of Early and Mild Alzheimer Disease: The AMARANTH and DAYBREAK-ALZ Randomized Clinical Trials. JAMA Neurol. 2020 Feb 1;77(2):199-209. doi: 10.1001/jamaneurol.2019.3988. Erratum In: JAMA Neurol. 2020 Sep 1;77(9):1179. doi: 10.1001/jamaneurol.2020.2416.
Cebers G, Alexander RC, Haeberlein SB, Han D, Goldwater R, Ereshefsky L, Olsson T, Ye N, Rosen L, Russell M, Maltby J, Eketjall S, Kugler AR. AZD3293: Pharmacokinetic and Pharmacodynamic Effects in Healthy Subjects and Patients with Alzheimer's Disease. J Alzheimers Dis. 2017;55(3):1039-1053. doi: 10.3233/JAD-160701.
Public notes

Contacts
Principal investigator
Name 0 0
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)
Address 0 0
Eli Lilly and Company
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02245737