| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10001896 |
| E.1.2 | Term | Alzheimer's disease |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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). |
|
| E.2.2 | Secondary objectives of the trial |
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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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
|
|
| E.4 | Principal 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 planning and conduct of the study (applies to both AZ staff or staff at the study site)
|
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Absolute change from baseline in ADAS-Cog to the end of the randomised treatment period (week 12). |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 65 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| End of study is defined as database lock, after which no patients will be exposed to study related activities. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 3 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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