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

AstraZeneca

Status and phase: Terminated; Phase 3; Phase 2

Conditions: Alzheimer´s Disease

Treatments: Drug: Lanabecestat; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT02245737

I8D-MC-AZES (Other Identifier)

D5010C00009 (Other Identifier)

16023

2014-002601-38 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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 until each of these substudies are completed.

Enrollment: 2,218 patients

Sex: All

Ages: 55 to 85 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

---

2,218 participants in 3 patient groups, including a placebo group

Lanabecestat 20 milligrams (mg)

Experimental group

Description:

Lanabecestat 20 mg given orally once daily for 104 weeks.

Treatment:

Drug: Lanabecestat

Lanabecestat 50 mg

Experimental group

Description:

Lanabecestat 50 mg given orally once daily for 104 weeks.

Treatment:

Drug: Lanabecestat

Placebo

Placebo Comparator group

Description:

Placebo given orally once daily for 104 weeks.

Treatment:

Drug: Placebo