Efficacy Study of a ZT-1 Implant in Patients Suffering From Alzheimer's Disease (BRAINz)

This is an interventional treatment trial for Moderate Alzheimer's Disease focused on measuring Alzheimer's disease, cognitive impairment, cholinesterase inhibitors, sustained-release implants, long acting treatment Read More

Inclusion Criteria:

1. Presence of moderately severe probable AD, diagnosed according to the DSM-IV and the NINCDS-ADRDA criteria;
2. MMSE score ≥ 14 and ≤ 22;
3. Male/female patient aged > 50 years; female patients should be of no child-bearing potential or postmenopausal (at least one year after last menses);
4. Body mass index (BMI) between 18 and 29 kg/m2 inclusive;
5. Has a caregiver, is living at home or in an assisted living facility, is able to attend ambulatory study visits;
6. Naïve to donepezil;
7. Has discontinued another AChEI and/or memantine at least 3 months prior to study visit 2 (Day 1);
8. Has a CT or MRI scan excluding another structural brain disease and supporting diagnosis of AD; CT or MRI scan must have been performed within 6 months prior to study visit 2 (Day 1, baseline);
9. Fluent in English (mother tongue or working language);
10. Able to communicate well with the Investigator;
11. Physically able to carry out functional tasks;
12. Has given written informed consent together with the caregiver.

Exclusion Criteria:

1. Presence of any disabling, severe or life-threatening disease (cardiac, respiratory, gastro-intestinal, neurological, epileptic, psychiatric, infectious, bone, endocrinologic);
2. Inability to discontinue at least 2 weeks prior to visit 2 (Day 1) (or within 5 drug half-lives, whichever is longer) any medication listed as prohibited;
3. Proven or clinically suspected other type of dementia such as vascular dementia, post-traumatic dementia, fronto-temporal dementia, dementia associated with Parkinson's Disease, infectious disease HIV, syphilis), folate or vitamin B12 deficiency, hypothyroidism etc.;
4. Significant liver impairment with ASAT, ALAT >=3x the upper normal limit at screening;
5. Significant kidney impairment with serum creatinine >=2x the upper normal limit at screening;
6. Presence of cardiac rhythm disorder, in particular bradycardia (< 60 bpm), conduction abnormalities such as AV block; presence of active ischaemia (such as unstable angina pectoris) or recent myocardial infarction, QT interval ≥ 450 msec at screening, QRS complex ≥ 110 msec at screening (ECG must be within normal limits at screening);
7. Uncontrolled arterial hypertension i.e. patients with systolic blood pressure (BP) >=160 mmHg and/or diastolic >=100 mmHg, at screening despite regular medication;
8. Uncontrolled arterial hypotension, i.e. patients with systolic BP ≤ 100 mmHg and/or presenting a fall of systolic BP ≥ 20 mmHg or a fall of diastolic BP >=10 mmHg after the 2 min Schellong test at screening;
9. Any concomitant disorder or resultant therapy that is likely to interfere with patient compliance or his/her participation to the study;
10. Participation in another study with an experimental drug within 3 months before study visit 2 (Day 1, baseline) or within 5 drug half-lives of the investigational drug (whichever is the longer);
11. Known peripheral cholinergic intolerance, i.e. with previously prescribed AChEI(s);
12. Known hypersensitivity to any of the test materials or related compounds, including lactose, present in the donepezil and placebo capsules;
13. Known active use of recreational drug or alcohol dependence, current alcohol abuse;
14. Inability to comply fully with the protocol;
15. Patients who, in the opinion of the Investigator, are considered unsuitable for any other reason.