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

NCT ID: NCT00423228

Last Updated: 2015-01-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

228 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-02-28

Study Completion Date

2009-04-30

Brief Summary

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Alzheimer's disease is characterised by memory loss and difficulties with thinking. These problems may be due to a deficiency in a brain chemical called acetylcholine. Acetylcholine helps transmit messages between nerve cells. Acetylcholine is degraded by an enzyme called "acetylcholinesterase". ZT-1 is a new drug derived from a plant extract already used in China for memory disorders, which blocks the action of the enzyme and restores adequate levels of acetylcholine.

This study will test the safety and efficacy of ZT-1 in the treatment of patients with Alzheimer's disease.

BRAINz stands for Better Recollection for Alzheimer's patients with the Implant of ZT-1.

Detailed Description

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This is a multicenter, randomised, double-blind, double-dummy, oral donepezil controlled study on the safety and efficacy of repeated monthly s.c. injections of a sustained-release implant of ZT 1 in patients with moderate Alzheimer's Disease.

The study enrolls patients aged \>50 years, with moderate AD with a MMSE score at study screening ≥14 and ≤22. The study aims to recruit 128 patients.

The study is divided into 3 periods:

1. A screening period
2. A 6-month treatment period, consisting of one month of titration with an oral medication and 5 months of treatment with an implant administered under the skin every 4 weeks. Oral treatment will be maintained throughout the treatment phase
3. A 2 week follow-up period.

Patients will be randomized in a 1:1 ratio to one of 2 groups: the ZT-1 (investigational product) treatment group or the donepezil (active comparator) treatment group.

The study comprises a total of 11 visits including screening and follow-up. An additional visit for PK/PD assessment is scheduled in about 10% of patients.

Conditions

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Moderate Alzheimer's Disease

Keywords

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Alzheimer's disease cognitive impairment cholinesterase inhibitors sustained-release implants long acting treatment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ZT-1

ZT-1 (investigational product)

Group Type EXPERIMENTAL

ZT-1

Intervention Type DRUG

Patients in the ZT-1 treatment group will receive ZT 1-1 mg capsules administered p.o. daily during the first month of treatment, followed by ZT-1 implants (9 mg) administered s.c. during the second month of treatment, followed by ZT-1 implants (12 mg) administered s.c. every 4 weeks during months 3 to 6 of treatment. Patients in the ZT-1 treatment group will receive dummy donepezil capsules during months 2 to 6 of the treatment period.

Donepezil

Donepezil

Group Type ACTIVE_COMPARATOR

Donepezil

Intervention Type DRUG

Patients in the donepezil treatment group will receive donepezil 5 mg capsules administered p.o. during the first month of treatment, followed by donepezil 10 mg/day during months 2 to 6 of the treatment period. Patients in the donepezil treatment group will also receive s.c. injections of dummy ZT 1 implants every 4 weeks during months 2 to 6 of the treatment period.

Interventions

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ZT-1

Patients in the ZT-1 treatment group will receive ZT 1-1 mg capsules administered p.o. daily during the first month of treatment, followed by ZT-1 implants (9 mg) administered s.c. during the second month of treatment, followed by ZT-1 implants (12 mg) administered s.c. every 4 weeks during months 3 to 6 of treatment. Patients in the ZT-1 treatment group will receive dummy donepezil capsules during months 2 to 6 of the treatment period.

Intervention Type DRUG

Donepezil

Patients in the donepezil treatment group will receive donepezil 5 mg capsules administered p.o. during the first month of treatment, followed by donepezil 10 mg/day during months 2 to 6 of the treatment period. Patients in the donepezil treatment group will also receive s.c. injections of dummy ZT 1 implants every 4 weeks during months 2 to 6 of the treatment period.

Intervention Type DRUG

Other Intervention Names

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Aricept

Eligibility Criteria

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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.
Minimum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Debiopharm International SA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emmanuel Tamches, MD

Role: STUDY_DIRECTOR

Debiopharm SA

Locations

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Central Coast Neuroscience Research

East Gosford, New South Wales, Australia

Site Status

Hornsby-Kuring-gai Health Service

Hornsby, New South Wales, Australia

Site Status

Southern Neurology

Kogarah, New South Wales, Australia

Site Status

The Prince Charles Hospital

Chermside, Queensland, Australia

Site Status

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status

The Queen Elizabeth Hospital

Woodville, South Australia, Australia

Site Status

St George's Hospital

Kew, Victoria, Australia

Site Status

Austin Health Repatriation Hospital

West Heidelberg, Victoria, Australia

Site Status

Hollywood Specialist Centre

Nedlands (Perth), Western Australia, Australia

Site Status

Calgary West Medical Centre

Calgary, Alberta, Canada

Site Status

Castledowns Medicentre

Edmonton, Alberta, Canada

Site Status

Saibal Nandy Professional Corporation

Medicine Hat, Alberta, Canada

Site Status

Parkwood Hospital

London, Ontario, Canada

Site Status

Toronto Memory Program

Toronto, Ontario, Canada

Site Status

Gerontion Research Inc.

Toronto, Ontario, Canada

Site Status

Neuro Rive-Sud

Montreal, Quebec, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

The Medical Arts Health Research Group

Kelowna, , Canada

Site Status

Douglas Hospital Research Center

Montreal, , Canada

Site Status

The Medical Arts Health Research Group

Penticton, , Canada

Site Status

OPMHS

Crowborough, East Sussex, United Kingdom

Site Status

Camden and Islington Mental Health Trust

London, London, United Kingdom

Site Status

Glasgow Memory Clinic

Glasgow, Scotland, United Kingdom

Site Status

Llandough Hospital

Penarth, Wales, United Kingdom

Site Status

Royal Blackburn Hospital

Blackburn, , United Kingdom

Site Status

North Manchester General Hospital

Manchester, , United Kingdom

Site Status

New Castle General Hospital

Newcastle upon Tyne, , United Kingdom

Site Status

MARC - Moorgreen Hospital

Southampton, , United Kingdom

Site Status

Countries

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Australia Canada United Kingdom

References

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Wilkinson D, Roughan L. The BRAINz trial: a novel approach to acetylcholinesterase-inhibitor treatment for Alzheimer's disease. Future Neurol 2(4):379-382,2007.

Reference Type BACKGROUND

Related Links

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http://www.debiopharm.com

Sponsor of the Study

http://www.alzheimers.org

Alzheimer's Disease Education and Referral (ADEAR) Center

Other Identifiers

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EUDRACT no. 2006-005161-18

Identifier Type: -

Identifier Source: secondary_id

DEB-ZTSR-201

Identifier Type: -

Identifier Source: org_study_id