Alzheimer's Disease MedDRA version: 12.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease
Conditions
Interventions
Product Code: AZD1446 2.5 mg
Pharmaceutical Form: Capsule, hard
CAS Number: 1025007-04-8
Current Sponsor code: AZD1446
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration numbe
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent from patient and caregiver before initiation of any study related procedures. Patients who are deemed incapable of providing informed consent may be enrolled if written informed consent has been obtained from the patient’s Legally Authorized Representative in accordance with local regulation 2. The patient and caregiver should understand, speak and read local language 3. The patient and the caregiver should be able to understand and comply with the requirements of the study, as judged by the investigator 4. Males and non-fertile females, 55-85 years, inclusive at day of enrollment 5. Clinical diagnosis of probable AD according to the NINCDS-ADRDA criteria 6. History of progressive worsening of memory and other cognitive functions for at least 12 months 7. A Hachinski Ischaemic Score =4, during enrollment (Visit 1). 8. CT or MRI scan within the past 6 months (performed after onset of dementia) consistent with the diagnosis of AD. If the CT/MRI test is older than 6 months, the patient will need to renew the CT/MRI to confirm the diagnosis 9. MMSE score 18-24 10. A body mass index (BMI=weight/height2) of 18-30 kg/m2 as calculated by the investigator at enrollment 11. Clcrea =60 mL/min estimated according to the formula by Cockcroft and Gault with S-Cr determined by Jaffe’s method (or if the enzymatic method is used, the S-Cr value used for calculating CLcrea should reflect the expected value as if the Jaffé method was used). 12. Male patients should be willing to use barrier contraception, ie, condoms, even if their partners are post-menopausal, surgically sterile or are using accepted contraceptive methods, from the first day of dosing until 3 months after the last dose of investigational product (IP) 13. Recordable P300 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Significant neurological disease or dementia other than AD, eg, mixed dementia, frontotemporal dementia and Parkinson’s disease, that may affect cognition or ability to complete the study 2. Possible, probable or definite vascular dementia in accordance with NINDS-AIREN criteria 3. Current major depressive disorder or other major psychiatric disorders according to the DSM-IV criteria 4. Current significant or unstable disease/disorder that, in the judgment of the investigator, is likely to deteriorate or affect the patient’s safety, influence cognitive assessments or affect ability to complete the study. 5. History of any malignant disease within the past 5 years with the exception of minor superficial skin diseases (ie, basal cell carcinoma and squamous cell carcinoma) 6. Poorly controlled diabetes mellitus, as judged by the investigator, or diabetes mellitus patient requiring any dose of insulin within the last 6 months. Insulin treated patients should be excluded since fluctuation in blood sugar may affect the cognitive assessments 7. Having known or suspected systemic serious infection (eg, HBV, HCV, HIV, tuberculosis) as judged by the investigator 8. Poorly controlled hypertension as judged by investigator 9. Myocardial infarction or acute coronary syndrome within the last year 10. Clinically significant ECG abnormalities as judged by the investigator based on assessment by a centrally located experienced cardiologist interpreting the ECG 11. Prolonged QTcF>450 msec or shortened QTcF upper limit of normal local lab reference limit, at enrollment) 16. Impaired vision and hearing making cognitive testing difficult as judged by the investigator 17. Women who are of childbearing potential, ie, not surgically sterile or post-menopausal for at least 12 months 18. Male patients planning to father a child or donate sperm during the study period and within 3 months after last intake of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of single and multiple dosing of AZD1446 and a single dose of donepezil on Quantified electroencephalography (qEEG) and Event-related potentials (ERP) in patients with mild-to-moderate AD.;Secondary Objective: 1. To evaluate the relationship between AZD1446/donepezil plasma concentrations and qEEG/ERP following single and multiple oral doses of AZD1446 and a single dose of donepezil, as applicable 2. To evaluate the correlation between changes in qEEG/ERP and changes in cognition, if applicable 3. To evaluate the time course of the effect on qEEG and ERP following different dosing regimens of AZD1446 4. To assess the safety and tolerability of single and multiple oral doses of AZD1446 in patients with AD. ;Primary end point(s): qEEG and event-related potentials (ERPs) will be measured to allow comparison of single and multiple oral administration of AZD1446 with single administration of donepezil compared to placebo: - qEEG parameters derived from measurements on the 28 electrodes - Event-related potentials (ERPs) measured by means of Auditory P300 and MMN variables from all 28 leads | — |
Countries
France
Outcome results
None listed