Study to assess the effect of AZD3293 in early Alzheimer's Disease

Phase 1

• Conditions: Early Alzheimer's Disease (mild cognitive impairment due to AD (ie,prodromal AD) and mild dementia of the Alzheimer's type); MedDRA version: 20.0Level: PTClassification code 10012271Term: Dementia Alzheimer's typeSystem Organ Class: 10029205 - Nervous system disorders; Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

• Registration Number: EUCTR2014-002601-38-IT
• Lead Sponsor: ELI LILLY & COMPANY, LILLY CORPORATE CENTER

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2018-10-04
• Study Start: 2021-01-20
• Last Update Posted: 4 April 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 2218

Inclusion Criteria

•Gradual and progressive change in the patient's memory function over more than 6 months
•Male or female, aged 55 to 85 years inclusive
•MMSE score of 20 to 30 inclusive
•Score of = 85 on the Delayed Memory Index of the Repeatable Battery for the assessment of Neuropsychological Status (RBANS)
•For a diagnosis of mild AD, patient (1) meets the National Institute on Aging (NIA) and the Alzheimer's Association (AA) (NIA-AA) criteria for
probable AD and (2) has a CDR global score of 0.5 or 1, with the memory box score =0.5
•For a diagnosis of MCI due to AD, patient (1) meets NIA-AA criteria for MCI due to AD and (2) had CDR global score of 0.5, with the memory box score =0.5
•Laboratory tests show no evidence of other etiologies for MCI or dementia
•PET visual reading or CSF Ab1-42 concentration positive for presence of amyloid
•Contraception: Women must be postmenopausal or surgically sterile.
Men must abstain or use barrier contraception from the first day of dosing until 3 months after the last dose and for 24 hours after amyloid scans
•Concomitant medication: The dose of any concomitant medication must be stable for at least 30 days before screening, and between screening
and randomization. For cholinesterase inhibitors (a) the dose regimen must be stable for at least 90 days prior to baseline, (b) the patient must be free from any clinically important side effects attributable to the drug, and (c) patient and study partner agree that, barring unforeseen circumstances, the dosage regimen will remain stable for the study
duration. Treatment with memantine must be discontinued at least 3 weeks before randomization.
•Agreement to undergo ApoE genotyping
•The patient must have a reliable study partner with whom he/she cohabits or has regular contact.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 136
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 768

Exclusion Criteria

•Prior or ongoing participation in any AZD3293 study or other BACE inhibitor study or participation in any other interventional AD study during the proposed study
•Significant neurological disease affecting the CNS, other than AD, that may affect cognition or ability to complete the study.
•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 or a concussion with sustained cognitive complaints or objective change in neuropsychological function in the last 5 years
•Patients with a current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) diagnosis of Major Depressive Disorder (MDD) or any current primary psychiatric diagnosis other than AD if, the psychiatric disorder or symptom is likely to confound interpretation of drug effect, affect cognitive assessment, or affect the patient's ability to complete the study, history of schizophrenia or other chronic psychosis
•History of alcohol, drug abuse or dependence (except nicotine dependence) within the last 2 years
•Within 1 year before the screening visit or between screening and baseline: myocardial infarction; moderate or severe congestive heart
failure, NYHA class III or IV; hospitalization for, or symptoms of, unstable angina; syncope due to orthostatic hypotension or unexplained syncope; known significant structural heart disease; or hospitalization for arrhythmia
•Congenital QT prolongation
•Intermittent second- or third-degree atrioventricular (AV) heart block or AV dissociation or history of ventricular tachycardia
•History of cancer within the last 5 years, with the exception of nonmetastatic 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 likely to affect cognitive assessment, deteriorate, or affect the patient's safety
or ability to complete the study , including hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic,
immunologic, or hematologic disorders
•History of vitiligo and/or current evidence of post-inflammatory hypopigmentation
•History of 2 or more clinically important drug allergies, eg, severe druginduced
rash or anaphylaxis
•Screening MRI shows evidence of significant abnormality that would suggest another potential etiology for MCI or dementia
•Uncontrolled hypertension
•A corrected QT (QTcF) interval measurement >470 msec
•Known positive serologic findings for HIV antibodies
•Positive hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies
•Urine drug screen positive for amphetamine, cocaine, phencyclidine, or barbiturate
•Any clinically important abnormality at screening
•Calculated creatinine clearance <30 mL/min
•ALT =2 × the upper limit of normal (ULN) of the performing laboratory, AST =2 × ULN, total bilirubin =1.5 × ULN or ALP =1.5 x ULN
•Regular use (eg, taken >3 days/week) of narcotic medications within 30 days before baseline
•Use of strong inhibitors of CYP3A4 within 14 days or 5 half-lives, whichever is longer, or strong inducers of CYP3A4 within 30 days before baseline
•Use of strong inhibitors of Pgp or BCRP within 14 days or 5 half-lives, whichever is longer, or inducers of Pgp within 30 days before baseline
•Use of drugs known to significantly prolong QT interval within 14 days
or 5 half-lives, whichever is long

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified