ClinicalTrials.gov
ClinicalTrials.gov Menu

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

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 evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02245737
Recruitment Status : Active, not recruiting
First Posted : September 22, 2014
Last Update Posted : July 9, 2018
Sponsor:
Collaborator:
AstraZeneca
Information provided by (Responsible Party):
Eli Lilly and Company

September 18, 2014
September 22, 2014
July 9, 2018
September 2014
October 1, 2018   (Final data collection date for primary outcome measure)
Change from Baseline on the 13-item Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog13) [ Time Frame: Baseline, Week 104 ]
Change in the Clinical Dementia Rating - Sum of Boxes (CDR-SB) score [ Time Frame: From baseline to Week 104 ]
Change in the Clinical Dementia Rating - Sum of Boxes (CDR-SB). Ratings are based on a semi-structured and in-depth interview with both patients and patient's study partner.
Complete list of historical versions of study NCT02245737 on ClinicalTrials.gov Archive Site
  • Change from Baseline on the Alzheimer´s Disease Cooperative Study Activities of Daily Living Inventory (ADCS-iADL) Instrumental Items [ Time Frame: Baseline, Week 104 ]
  • Change from Baseline on the Functional Activities Questionnaire (FAQ) Score [ Time Frame: Baseline, Week 104 ]
  • Change from Baseline on the Integrated Alzheimer's Disease Rating Scale (iADRS) Score [ Time Frame: Baseline, Week 104 ]
  • Change from Baseline on the Clinical Dementia Rating - Sum of Boxes (CDR-SB) Score [ Time Frame: Baseline, Week 104 ]
  • Time in Clinical Dementia Rating (CDR) Global Score Stage [ Time Frame: Baseline through Loss of 1 Global Stage or Week 104 ]
  • Change from Baseline in Neuropsychiatric Inventory (NPI) Score [ Time Frame: Baseline, Week 104 ]
  • Change from Baseline on the Mini-Mental Status Examination (MMSE) [ Time Frame: Baseline, Week 104 ]
  • Pharmacodynamics (PD): Change from Baseline in Concentration of Cerebrospinal Fluid (CSF) Biomarker Aβ1-42 [ Time Frame: Baseline, Week 97 ]
  • PD: Change from Baseline in Concentration of CSF Biomarker Aβ1-40 [ Time Frame: Baseline, Week 97 ]
  • Change from Baseline in CSF Total Tau [ Time Frame: Baseline, Week 104 ]
  • Change from Baseline in CSF Phosphorylated Tau [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Amyloid Imaging Positron Emission Tomography (AV-45 PET) [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in Tau PET [ Time Frame: Baseline, Week 104 ]
  • Change From Baseline in PET Using Fluorine-18 Fluorodeoxyglucose (18F-FDG) [ Time Frame: Baseline, Week 104 ]
  • Change from Baseline in Whole Brain Volume [ Time Frame: Baseline, Week 104 ]
  • Population Pharmacokinetics (PK): Apparent Oral Clearance of Lanabecestat [ Time Frame: Week 4 through Week 91 ]
  • Population PK: Central Volume of Distribution of Lanabecestat [ Time Frame: Week 4 through Week 91 ]
  • Change in Alzheimer´s Disease Assessment Scale- Cognitive subscale (ADAS-Cog-13) score [ Time Frame: From baseline to Week 104 ]
    Change in Alzheimer´s Disease Assessment Scale- Cognitive subscale (ADAS-Cog-13) score
  • Change in Functional Activities Questionnaire (FAQ) score [ Time Frame: From baseline to Week 104 ]
    Change in Functional Activities Questionnaire (FAQ) score
  • Change in Alzheimer´s disease Cooperative Study Activities of Daily Living inventory (ADCS-ADL) instrumental items score [ Time Frame: From baseline to Week 104 ]
    Change in Alzheimer´s disease Cooperative Study Activities of Daily Living inventory (ADCS-ADL) instrumental items score
  • Change in Clinical Dementia Rating (CDR) Global Score [ Time Frame: From Loss of 1 Global Stage through Week 104 ]
    Change in Clinical Dementia Rating (CDR) global score
  • Change in Neuropsychiatric Inventory (NPI) score [ Time Frame: From baseline to Week 104 ]
    To evaluate the efficacy on neuropsychiatric symptoms as assessed by Neuropsychiatric Inventory (NPI) score
  • Change in Cerebrospinal fluid (CSF) biomarkers [ Time Frame: From baseline to Week 97 ]
    To evaluate the effect of AZD3293 on central markers of pharmacodynamics and neurodegeneration by assessing cerebrospinal fluid (CSF) concentrations
  • Change in Positron emission tomography (PET) [ Time Frame: From baseline to Week 104 ]
    To evaluate the effect of AZD3293 on brain amyloid burden and brain metabolic rates.
  • Change in Magnetic Resonance imaging (MRI) [ Time Frame: From screening to Week 104 ]
    To evaluate the effect of AZD3293 on underlying pathology
Not Provided
Not Provided
 
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)
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.
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 until each of these substudies are completed.
Interventional
Phase 2
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Alzheimer´s Disease
  • Drug: Lanabecestat
    Administered orally
    Other Names:
    • LY3314814
    • AZD3293
  • Drug: Placebo
    Administered orally
  • Experimental: Lanabecestat 20 mg
    Lanabecestat 20 milligrams (mg) given orally once daily for 104 weeks.
    Intervention: Drug: Lanabecestat
  • Experimental: Lanabecestat 50 mg
    Lanabecestat 50 mg given orally once daily for 104 weeks.
    Intervention: Drug: Lanabecestat
  • Placebo Comparator: Placebo
    Placebo given orally once daily for 104 weeks.
    Intervention: Drug: Placebo
Cebers G, Alexander RC, Haeberlein SB, Han D, Goldwater R, Ereshefsky L, Olsson T, Ye N, Rosen L, Russell M, Maltby J, Eketjäll 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
2202
1551
October 1, 2018
October 1, 2018   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
55 Years to 85 Years   (Adult, Older Adult)
No
Contact information is only displayed when the study is recruiting subjects
Australia,   Belgium,   Canada,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Poland,   Puerto Rico,   Romania,   Spain,   United Kingdom,   United States
Argentina,   Czech Republic,   Sweden
 
NCT02245737
16023
I8D-MC-AZES ( Other Identifier: Eli Lilly and Company )
2014-002601-38 ( EudraCT Number )
D5010C00009 ( Other Identifier: AstraZeneca )
Yes
Not Provided
Plan to Share IPD: Yes
Plan Description:

Lilly provides access to the individual patient data from studies on approved medicines and indications as defined by the sponsor specific information on ClinicalStudyDataRequest.com.

This access is provided in a timely fashion after the primary publication is accepted. Researchers need to have an approved research proposal submitted through ClinicalStudyDataRequest.com. Access to the data will be provided in a secure data sharing environment after signing a data sharing agreement.

Eli Lilly and Company
Eli Lilly and Company
AstraZeneca
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
Eli Lilly and Company
July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP