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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: 20.0 Level: PT Classification code 10012271 Term: Dementia Alzheimer's type System Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Registration Number
EUCTR2014-002601-38-DE
Lead Sponsor
Eli Lilly and Company
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
Not specified
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) has a 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, surgically sterile or infertile due to congenital abnormality. Men must abstain or use barrier contraception from the first day of dosing until 3 months after the last dose and abstain for 24 hours after amyloid PET scans
•All medication dosing should be stable for at least 30 days before screening, and between screening and randomization (does not apply to medications discontinued during screening, medications taken as needed, and/ or medications not expected to substantially influence safety or efficacy assessments, in the opinion of the investigator, at baseline).
•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 another clinical trial or medical research judged not to be scientifically or medically compatible
•Significant and/or current 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 DSM-V diagnosis of Major Depressive Disorder 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; hospitalization for arrhythmia
•Congenital QT prolongation
•Intermittent second- or third-degree AV heart block or AV dissociation or history of ventricular tachycardia
•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 or cancers with low risk of recurrence or spread
•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 or exposure to depigmenting agents in the 6 months prior to screening
•History of 2 or more clinically important drug allergies, eg, severe drug-induced 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
•Positive serologic findings for HIV antibodies
•Positive hepatitis B surface antigen or hepatitis C virus antibodies
•Urine drug screen positive for inappropriate drug use
•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
•Use of medications that would interfer with cognitive testing
•Use of st

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Secondary Outcome Measures
NameTimeMethod
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