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

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2015 by Eli Lilly and Company
Information provided by (Responsible Party):
Eli Lilly and Company Identifier:
First received: September 18, 2014
Last updated: November 19, 2015
Last verified: November 2015
The purpose of this study is to assess the efficacy and safety of LY3314814 compared with placebo administered for 104 weeks in the treatment of early Alzheimer´s disease. The study will test the hypothesis that LY3314814 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 in the Clinical Dementia Rating-Sum of Boxes score at week 104 in each of the 2 LY3314814 treatment groups compared with placebo.

Condition Intervention Phase
Alzheimer´s Disease
Drug: LY3314814
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official 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)

Resource links provided by NLM:

Further study details as provided by Eli Lilly and Company:

Primary Outcome Measures:
  • Change from Baseline in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change from Baseline in Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog-13) Score [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Change from Baseline in Functional Activities Questionnaire (FAQ) Score [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Change from Baseline in Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) Instrumental Items Score [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Change in Clinical Dementia Rating (CDR) Global Score [ Time Frame: From Loss of 1 Global Stage through Week 104 ] [ Designated as safety issue: No ]
  • Change from Baseline in Neuropsychiatric Inventory (NPI) Score [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Pharmacodynamics (PD): Change from Baseline in Concentration of Cerebrospinal fluid (CSF) Biomarker Aβ1-42 [ Time Frame: Baseline, Week 97 ] [ Designated as safety issue: No ]
  • PD: Change from Baseline in Concentration of CSF Biomarker Aβ1-40 [ Time Frame: Baseline, Week 97 ] [ Designated as safety issue: No ]
  • Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Change From Baseline in PET Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Change from Baseline in Cerebral Spinal Fluid (CSF) Total Tau [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Change from Baseline in CSF Partial Tau [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Change from Baseline in Whole Brain Volume [ Time Frame: Baseline, Week 104 ] [ Designated as safety issue: No ]
  • Population Pharmacokinetics (PK): Apparent Oral Clearance of LY3314814 [ Time Frame: Week 4 through Week 91 ] [ Designated as safety issue: No ]
  • Population PK: Central Volume of Distribution of LY3314814 [ Time Frame: Week 4 through Week 91 ] [ Designated as safety issue: No ]

Estimated Enrollment: 2202
Study Start Date: September 2014
Estimated Study Completion Date: August 2021
Estimated Primary Completion Date: August 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: LY3314814 20 mg
LY3314814 20 milligrams (mg) given orally once daily for 104 weeks.
Drug: LY3314814
Administered orally
Other Name: AZD3293
Experimental: LY3314814 50 mg
LY3314814 50 mg given orally once daily for 104 weeks.
Drug: LY3314814
Administered orally
Other Name: AZD3293
Placebo Comparator: Placebo
Placebo given orally once daily for 104 weeks.
Drug: Placebo
Administered orally

Detailed Description:
Participants who meet other study entry requirements will be required to undergo either an amyloid positron emission tomography (PET) scan or a lumbar puncture for cerebrospinal fluid (CSF) sampling at screening to document presence of abnormal levels of brain and CSF amyloid for study inclusion. The study includes 2 sub-studies: the participants that undergo a PET scan at screening will be included in the PET-substudy, and participants who undergo a lumbar puncture at screening will be included in the CSF substudy.

Ages Eligible for Study:   55 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

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, or non-progressive prostate cancer
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT02245737

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559

  Show 219 Study Locations
Sponsors and Collaborators
Eli Lilly and Company
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
  More Information

No publications provided

Responsible Party: Eli Lilly and Company Identifier: NCT02245737     History of Changes
Other Study ID Numbers: 16023, I8D-MC-AZES, 2014-002601-38, D5010C00009
Study First Received: September 18, 2014
Last Updated: November 19, 2015
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Department of Health and Ageing Therapeutic Goods Administration
Belgium: Federal Agency for Medicinal Products and Health Products
Canada: Health Canada
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Hungary: National Institute of Pharmacy
Japan: Pharmaceuticals and Medical Devices Agency
Germany: Paul-Ehrlich-Institut
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
South Korea: Ministry of Food and Drug Safety
Romania: National Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Food and Drug Administration
Italy: The Italian Medicines Agency
Sweden: Medical Products Agency

Keywords provided by Eli Lilly and Company:
Alzheimer's disease
Brain Diseases
Neurogenerative Diseases
Central Nervous System Diseases
Nervous System Diseases
Mental Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Nervous System Diseases
Neurodegenerative Diseases
Tauopathies processed this record on November 27, 2015