AMARANTH

TerminatedPhase 2 / PHASE3Results posted

An Efficacy and Safety Study of Lanabecestat (LY3314814) in Early Alzheimer's Disease

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)

Lead sponsor

AstraZeneca

Asset

Lanabecestat

Listed sites

254

Recruiting sites

Enrollment

2,218

actual

Study population

Alzheimer’s disease

Key I/E criteria

•MCI due to AD•MMSE 20-30

Primary endpoint

•ADAS-Cog

Footprint

Where this trial recruits

Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

Org study ID16023

Eudract number2014-002601-38

Secondary IDD5010C00009AstraZeneca

Secondary IDI8D-MC-AZESEli Lilly and Company

NCT IDNCT02245737

Timeline

Milestones

Study first posted2014-09-22estimated

Study start2014-09-30actual

Primary completion2018-10-04actual

Study completion2018-10-04actual

Results first posted2019-08-06actual

Last update posted2019-12-03actual

Assets

Drug assets

Lanabecestat

Study populations

Who this study enrolls

Alzheimer’s disease

Eligibility

Who can enroll

Minimum age55 Years

Maximum age85 Years

SexAll

Healthy volunteersNot accepted

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

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

Endpoints (34)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Global cognition

Amyloid biomarkers

Tau biomarkers

Function / daily living

Neuroimaging

Behavior / neuropsychiatric

Safety / tolerability / PK

Other (unclassified)

Global cognition

8 endpoints

Primary/protocol endpoint

Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)

Time frame:Baseline, Week 104

ADAS-Cog

change from baseline, improvement

Primary/registry result

Change From Baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13)

Time frame:Baseline, Week 104

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=723 Participants	10.31	0.55
Lanabecestat 20 mgn=722 Participants	9.38	0.56
Lanabecestat 50 mgn=708 Participants	10.72	0.58

LS Mean Difference (Final Values)-0.9395% CI-2.447 - 0.594p0.232Mixed Models Analysis

LS Mean Difference (Final Values)0.4195% CI-1.124 - 1.947p0.599Mixed Models Analysis

Secondary/protocol endpoint

Change From Baseline on the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score

Time frame:Baseline, Week 104

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Secondary/protocol endpoint

Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage

Time frame:Baseline through Loss of 1 Global Stage or Week 104

time to event, event

Secondary/protocol endpoint

Change From Baseline on the Mini-Mental State Examination (MMSE)

Time frame:Baseline, Week 104

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Secondary/registry result

Change From Baseline on the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score

Time frame:Baseline, Week 104

Clinical Dementia Rating-Sum of Boxes (CDR-SB)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=704 Participants	3.02	0.17
Lanabecestat 20 mgn=705 Participants	3.17	0.17
Lanabecestat 50 mgn=676 Participants	3.17	0.18

LS Mean Difference (Final Values)0.1595% CI-0.322 - 0.622p0.533Mixed Models Analysis

LS Mean Difference (Final Values)0.1595% CI-0.328 - 0.630p0.537Mixed Models Analysis

Secondary/registry result

Time to Progression as Measured by Loss of Clinical Dementia Rating (CDR) Global Score Stage

Time frame:Baseline through Loss of 1 Global Stage or Week 104

time to event, event

Posted result

Group	Value (median), Days	Reported bounds
Placebon=716 Participants	548	-547 - 554
Lanabecestat 20 mgn=714 Participants	547	-545 - 550
Lanabecestat 50 mgn=696 Participants	548	-545 - 553

Secondary/registry result

Change From Baseline on the Mini-Mental State Examination (MMSE)

Time frame:Baseline, Week 104

Mini-Mental State Examination (MMSE)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=723 Participants	-5.50	0.26
Lanabecestat 20 mgn=725 Participants	-5.18	0.26
Lanabecestat 50 mgn=709 Participants	-5.49	0.27

LS Mean Difference (Final Values)0.3295% CI-0.391 - 1.027p0.379Mixed Models Analysis

LS Mean Difference (Final Values)0.0095% CI-0.714 - 0.721p0.992Mixed Models Analysis

Function / daily living

4 endpoints

Secondary/protocol endpoint

Change From Baseline on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL)

Time frame:Baseline, Week 104

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline on the Functional Activities Questionnaire (FAQ) Score

Time frame:Baseline, Week 104

change from baseline, improvement

Secondary/registry result

Change From Baseline on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory Instrumental Items (ADCS-iADL)

Time frame:Baseline, Week 104

ADCS-Activities of Daily Living (ADCS-ADL)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=702 Participants	-8.87	0.60
Lanabecestat 20 mgn=700 Participants	-8.84	0.61
Lanabecestat 50 mgn=674 Participants	-8.79	0.63

LS Mean Difference (Final Values)0.0395% CI-1.609 - 1.669p0.971Mixed Models Analysis

LS Mean Difference (Final Values)0.0895% CI-1.580 - 1.743p0.923Mixed Models Analysis

Secondary/registry result

Change From Baseline on the Functional Activities Questionnaire (FAQ) Score

Time frame:Baseline, Week 104

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=699 Participants	6.09	0.38
Lanabecestat 20 mgn=697 Participants	5.96	0.39
Lanabecestat 50 mgn=674 Participants	6.71	0.40

LS Mean Difference (Final Values)-0.1495% CI-1.172 - 0.899p0.796Mixed Models Analysis

LS Mean Difference (Final Values)0.6195% CI-0.437 - 1.660p0.252Mixed Models Analysis

Behavior / neuropsychiatric

2 endpoints

Secondary/protocol endpoint

Change From Baseline in Neuropsychiatric Inventory (NPI) Score

Time frame:Baseline, Week 104

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Secondary/registry result

Change From Baseline in Neuropsychiatric Inventory (NPI) Score

Time frame:Baseline, Week 104

Neuropsychiatric Inventory (NPI)

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=697 Participants	3.22	0.81
Lanabecestat 20 mgn=695 Participants	4.99	0.83
Lanabecestat 50 mgn=663 Participants	4.67	0.85

LS Mean Difference (Final Values)1.7795% CI-0.441 - 3.986p0.116Mixed Models Analysis

LS Mean Difference (Final Values)1.4595% CI-0.808 - 3.704p0.208Mixed Models Analysis

Amyloid biomarkers

6 endpoints

Secondary/protocol endpoint

Pharmacodynamics (PD): Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42

Time frame:Baseline, Week 97

percent change from baseline, improvement

Secondary/protocol endpoint

PD: Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40

Time frame:Baseline, Week 97

percent change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan

Time frame:Baseline, Week 104

Amyloid PET Centiloid

change from baseline, improvement

Secondary/registry result

Pharmacodynamics (PD): Percent Change From Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Amyloid Beta (Aβ)1-42

Time frame:Baseline, Week 97

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percent change in Aβ1-42	Standard error
Placebon=63 Participants	-2.64	2.07
Lanabecestat 20 mgn=66 Participants	-53.91	2.04
Lanabecestat 50 mgn=79 Participants	-68.13	1.87

LS Mean Difference (Final Values)-51.2795% CI-56.963 - -45.578p<0.001ANCOVA

LS Mean Difference (Final Values)-65.4895% CI-70.947 - -60.022p<0.001ANCOVA

Secondary/registry result

PD: Percent Change From Baseline in Concentration of CSF Biomarker Aβ1-40

Time frame:Baseline, Week 97

percent change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Percent change in Aβ1-40	Standard error
Placebon=64 Participants	-1.92	1.77
Lanabecestat 20 mgn=66 Participants	-59.90	1.74
Lanabecestat 50 mgn=79 Participants	-75.17	1.60

LS Mean Difference (Final Values)-57.9995% CI-62.865 - -53.108p<0.001ANCOVA

LS Mean Difference (Final Values)-73.2595% CI-77.926 - -68.575p<0.001ANCOVA

Secondary/registry result

Change From Baseline in Brain Amyloid Burden Using Florbetapir Amyloid Positron Emission Tomography (PET) Scan

Time frame:Baseline, Week 104

Amyloid PET Centiloid

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=133 Participants	-2.08	1.86
Lanabecestat 20 mgn=127 Participants	-15.76	1.89
Lanabecestat 50 mgn=116 Participants	-19.74	1.97

LS Mean Difference (Final Values)-13.6895% CI-18.785 - -8.574p<0.001ANCOVA

LS Mean Difference (Final Values)-17.6695% CI-22.887 - -12.428p<0.001ANCOVA

Tau biomarkers

6 endpoints

Secondary/protocol endpoint

Change From Baseline in CSF Total Tau

Time frame:Baseline, Week 97

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in CSF Phosphorylated Tau

Time frame:Baseline, Week 97

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Tau PET ((Flortaucipir F18)

Time frame:Baseline, Week 104

change from baseline, improvement

Secondary/registry result

Change From Baseline in CSF Total Tau

Time frame:Baseline, Week 97

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Picogram per milliliter (pg/mL)	Standard error
Placebon=64 Participants	12.39	8.05
Lanabecestat 20 mgn=66 Participants	-7.48	8.01
Lanabecestat 50 mgn=79 Participants	-2.92	7.30

LS Mean Difference (Final Values)-19.8795% CI-42.210 - 2.464p0.081ANCOVA

LS Mean Difference (Final Values)-15.3195% CI-36.555 - 5.938p0.157ANCOVA

Secondary/registry result

Change From Baseline in CSF Phosphorylated Tau

Time frame:Baseline, Week 97

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Picogram per milliliter (pg/mL)	Standard error
Placebon=63 Participants	0.47	0.95
Lanabecestat 20 mgn=66 Participants	-2.16	0.94
Lanabecestat 50 mgn=79 Participants	-1.66	0.85

LS Mean Difference (Final Values)-2.6295% CI-5.243 - -0.002p0.050ANCOVA

LS Mean Difference (Final Values)-2.1295% CI-4.618 - 0.373p0.095ANCOVA

Secondary/registry result

Change From Baseline in Tau PET ((Flortaucipir F18)

Time frame:Baseline, Week 104

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Standard Uptake Value ratio (SUVr)	Standard error
Placebon=97 Participants	0.04	0.01
Lanabecestat 20 mgn=94 Participants	0.03	0.01
Lanabecestat 50 mgn=93 Participants	0.03	0.01

LS Mean Difference (Final Values)-0.0195% CI-0.033 - 0.014p0.426ANCOVA

LS Mean Difference (Final Values)-0.0195% CI-0.029 - 0.018p0.660ANCOVA

Neuroimaging

4 endpoints

Secondary/protocol endpoint

Change From Baseline in Brain Metabolism Using Fluorodeoxyglucose (FDG)

Time frame:Baseline, Week 104

change from baseline, improvement

Secondary/protocol endpoint

Change From Baseline in Whole Brain Volume

Time frame:Baseline, Week 104

change from baseline, improvement

Secondary/registry result

Change From Baseline in Brain Metabolism Using Fluorodeoxyglucose (FDG)

Time frame:Baseline, Week 104

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Standard Uptake Value ratio (SUVr)	Standard error
Placebon=83 Participants	-0.04	0.00
Lanabecestat 20 mgn=95 Participants	-0.05	0.00
Lanabecestat 50 mgn=82 Participants	-0.05	0.00

LS Mean Difference (Final Values)-0.0195% CI-0.015 - 0.003p0.210ANCOVA

LS Mean Difference (Final Values)-0.0095% CI-0.013 - 0.007p0.568ANCOVA

Secondary/registry result

Change From Baseline in Whole Brain Volume

Time frame:Baseline, Week 104

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), cm^3 (cubic centimeter)	Standard error
Placebon=565 Participants	-14.16	0.34
Lanabecestat 20 mgn=582 Participants	-16.49	0.33
Lanabecestat 50 mgn=550 Participants	-17.34	0.34

LS Mean Difference (Final Values)-2.3495% CI-3.258 - -1.413p<0.001ANCOVA

LS Mean Difference (Final Values)-3.1895% CI-4.118 - -2.247p<0.001ANCOVA

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Pharmacokinetics (PK): Plasma Concentration of Lanabecestat

Time frame:Week 4, post dose prior to departure from the clinic

concentration, descriptive

Secondary/registry result

Pharmacokinetics (PK): Plasma Concentration of Lanabecestat

Time frame:Week 4, post dose prior to departure from the clinic

concentration, descriptive

Posted result

Group	Value (mean), nanograms per milliliter (ng/mL)	Standard deviation
Lanabecestat 20 mgn=697 Participants	67.7	49.1
Lanabecestat 50 mgn=662 Participants	213	149

Other (unclassified)

2 endpoints

Secondary/protocol endpoint/low confidence

Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score

Time frame:Baseline, Week 104

ADAS-Cog

change from baseline, improvement

Secondary/registry result/low confidence

Change From Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score

Time frame:Baseline, Week 104

ADAS-Cog

change from baseline, improvement

Posted result

Group	Value (least_squares_mean), Units on a scale	Standard error
Placebon=696 Participants	-19.56	0.99
Lanabecestat 20 mgn=689 Participants	-18.45	1.02
Lanabecestat 50 mgn=662 Participants	-19.69	1.05

LS Mean Difference (Final Values)1.1195% CI-1.637 - 3.852p0.428Mixed Models Analysis

LS Mean Difference (Final Values)-0.1395% CI-2.918 - 2.655p0.926Mixed Models Analysis

Publications (4)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 21, 2026

Endpoint classificationDelfa ADRD endpoint taxonomy

Results tableClinicalTrials.gov results section

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 21, 2026 snapshot.