Alzheimer's Disease MedDRA version: 9.1 Level: LLT Classification code 10001896 Term: Alzheimer's disease
Conditions
Interventions
Trade Name: Aricept 5 mg film coated tablet
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Donepezil hydrochloride
CAS Number: 120014-06-4
Concentration unit: mg milligram(s)
Concentrati
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Provision of written informed consent 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 Acceptable Representative in accordance with local regulations 2. Provision of written informed consent from the caregiver 3. Female and male, aged 60 to 85 years, at day of enrolment 4. Clinical diagnosis of probable AD according to the NINCDS-ADRDA criteria 5. Computerised tomography (CT) or Magnetic resonance imaging (MRI) scan within the past 2 years (performed after onset of dementia) consistent with the diagnosis of AD 6. MMSE score of 12-26 7. Lives with appropriate caregiver at home, or in a community dwelling with caregiver capable of accompanying patient on all clinic visits and visiting the patient at least three times per week for the duration of the study 8. Patient and caregiver understand, speak and read local language 9. Be able to understand and comply with the requirements of the study, as judged by the investigator. For inclusion in the optional exploratory genetic research at Visit 4, patients must fulfil the following criterion: 1. Provision of informed consent for optional exploratory genetic research. Patients who are deemed incapable of providing informed consent may be enrolled if written informed consent has been obtained from the patient’s Legally Authorised Representative in accordance with local regulations 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, e.g. Parkinson Disease Dementia, that may affect cognition or ability to complete the study 2. Current major depressive disorder or other major psychiatric disorders according to the DSM-IV criteria 3. Use of AChEIs or memantine for treatment of AD within 8 weeks prior to Visit 1 (enrolment visit) and during the study (except investigational drug after randomisation) 4. Use of smoking cessation therapy within 4 weeks prior to Visit 1 (enrolment visit) and during the study. Smoking cessation therapy include bupropion, varenicline and any dosage form of nicotine replacement therapy 5. Use of certain drugs with narrow therapeutic range, specified in Section 3.7, from Visit 1 (enrolment visit) and during the study. Exception for amiodarone, which is not allowed within 10 weeks of enrolment 6. Use of Ginkgo Biloba and certain concomitant therapy with anticholinergic effect, specified in Section 3.7, unless on a constant stable dose during the last 4 weeks prior to Visit 1 (enrolment visit) and during the study 7. Not suitable for donepezil treatment according to current country-specific label 8. Current significant major or unstable respiratory disease, heart disease, cerebrovascular disease, haematological disease, hepatic disease, renal disease, gastrointestinal disease or other major disease as judged by the investigator. 9. Myocardial infarction or acute coronary syndrome within the last year 10. Having a known or suspected hypothyreosis, vitamin B12 or folic acid deficiency as judged by the investigator. Patients with substituted hypothyreosis or vitamin B12 or folic acid deficiency and laboratory values within normal limits can be included 11. Poorly controlled hypertension as judged by the investigator 12. Patients with diabetes mellitus with the exception of stable diabetes controlled on diet alone for at least 3 months before Visit 1 (enrolment visit), as judged by the investigator. 13. Having known or suspected systemic infection (e.g. Hepatitis B virus [HBV], Hepatitis C virus [HCV], Human immunodeficiency virus [HIV], tuberculosis) as judged by the investigator 14. Current systemic illness 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 15. History of any malignant disease within the past 5 years with the exception of minor superficial skin diseases (i.e., basal cell carcinoma and squamous cell carcinoma) 16. Impaired vision and hearing making cognitive testing difficult as judged by the investigator 17. Known or suspected drug or alcohol abuse as judged by the investigator 18. Clinically significant ECG abnormalities as judged by the investigator based on assessment by a centrally located experienced cardiologist interpreting the ECG 19. Clinically significant abnormal laboratory values as judged by the investigator 20. Clinically significant abnormal findings in physical examination or vital signs as judged by the investigator 21. Previous bone marrow or stem cell transplant 22. Received blood transfusion in the 120-day period preceding the date of genetic sample collection. 23. Participation in other clinical trial, use of any investigational drugs or procedures or use of experimental medications within 30 days prior to Visit 1 (enrolment visit) 24. Previous participation in this study 25. Involvement in the planni
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prove the concept that AZD3480 improves cognition in Alzheimer's disease patients in relation to placebo and donepezil, assessed as change from baseline on Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog).;Secondary Objective: 1. To compare donepezil to placebo, as assessed by change from baseline on ADAS-Cog, to provide assay sensitivity in the event that AZD3480 is not able to ensure this 2. To assess dose response relationship in cognitive effects of 3 dose groups of AZD3480 compared to placebo in changes from baseline on ADAS-Cog and Alzheimer’s disease Cooperative Study- Clinical Global Impression of Change 3. To assess effects on cognition of 3 dose groups of AZD3480 compared to placebo in changes from baseline by use of computerised cognitive test battery and Mini Mental State Examination 4. To assess effects on cognition of 3 dose groups of AZD3480 compared to placebo in changes from baseline evaluated by Patient Reported Outcomes 5. To assess the population pharmacokinetics and explore the exposure response relationship of AZD3480 6. To evaluate safety and tolerability of AZD3480 by assessment of adverse events, laboratory variables, vital signs and physical examinations;Primary end point(s): Absolute change from baseline in ADAS-Cog to the end of the randomised treatment period (week 12). | — |
Countries
Austria, Bulgaria, Czech Republic, Germany, Spain, United Kingdom
Outcome results
None listed