E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
mild to moderate Alzheimer’s Disease (AD) |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10011762 |
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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 assess safety and tolerance of two ZT-1 dose levels (1.5 mg, 2 mg 1x/d) compared to placebo and donepezil in patients with mild to moderate AD
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E.2.2 | Secondary objectives of the trial |
To assess the efficacy of two ZT-1 dose levels (1.5 mg, 2 mg 1x/d) to improve cognitive function compared to placebo and donepezil in patients with mild to moderate AD To assess the efficacy of two ZT-1 dose levels (1.5 mg, 2 mg 1x/d) to improve behavioural, overall and functional outcomes compared to placebo and donepezil in patients with mild to moderate AD
To measure plasma concentrations of ZT-1, its active metabolite huperzine A and its inactive metabolite 5-Cl-o-vanilline for a subsequent population pharmacokinetic analysis of pooled data to establish standard pharmacokinetic parameters
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients with mild to moderately severe probable AD, diagnosed according to the DSM-IV and the criteria of NINCDS-ARDRA.
MMSE score at study entry ³12 and £ 26.
Patients should be aged >60 years.
Patients should be ambulatory and have a caregiver/informant willing to be present at each assessment.
Subjects should be physically able to carry out functional tasks.
Computed tomographic or magnetic resonance imaging to exclude other structural brain disease performed within 6 months before study start should support diagnosis of AD.
Patients must provide a written informed consent together with the caregiver. |
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E.4 | Principal exclusion criteria |
Presence of any disabling, severe or life-threatening disease (cardiac, respiratory, gastro-intestinal, neurological, epileptic, psychiatric, infectious, bone, endocrinologic).
Inability to discontinue at least 2 weeks prior to study start any medication listed as prohibited (see section 7.5.2 Prohibited medications).
Prior use of cholinesterase inhibitors.
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.
Significant liver impairment : ASAT, ALAT ³ 3 times the upper normal limit.
Presence of cardiac rhythm disorder, in particular bradycardia or conduction abnormalities (ECG within normal limits at prestudy).
Uncontrolled arterial hypertension i.e. subjects with systolic BP ³160 mm Hg and/or diastolic ³100 mmHg, despite regular medication.
Significant kidney impairment: serum creatinine ³ 2 times the upper normal limit.
Any concomitant disorder or resultant therapy that is likely to interfere with subject compliance or with the study.
Participation in another study with an experimental drug within 3 months before study start or within 5 drug half-lives of the investigational drug (whichever is the longer).
Known hypersensitivity to any of the test materials or related compounds.
Known active use of recreational drug or alcohol dependence, current alcohol abuse.
Inability to give written informed consent together with the caregiver or to comply fully with the protocol.
Subjects who, in the opinion of the Investigator, are considered unsuitable for any other reason. |
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E.5 End points |
E.5.1 | Primary end point(s) |
(Co-primary endpoints:)
Change in ADAS-cog conventional from pre-treatment to Week 12.
Change in ADAS-cog extended version from pre-treatment to Week 12.
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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 | Information not present in EudraCT |
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) | Information not present in EudraCT |
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) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
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.8.5 | The trial involves multiple Member States | Yes |
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 |
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E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
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
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the trial ends at the llast visit of the last subject |
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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 | 2 |
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 | 10 |