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

This study has been completed.
Sponsor:
Information provided by:
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT00423228
First received: January 17, 2007
Last updated: August 9, 2011
Last verified: August 2011
  Purpose

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.


Condition Intervention Phase
Moderate Alzheimer's Disease
Drug: ZT-1
Drug: Donepezil
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomised, Double-blind, Double-dummy, Oral Donepezil Controlled Study on the Safety and Efficacy of Repeated Monthly Subcutaneous Injections of a Sustained-release Implant of ZT 1 in Patients With Moderate Alzheimer's Disease

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • Change in the MMSE score from baseline to week 25 [ Time Frame: baseline to week 25 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Responder rate as defined by at least 2 points improvement in the MMSE score; [ Time Frame: baseline to week 25 ] [ Designated as safety issue: No ]
  • Change on the ADAS-Cog 11 items subscale; [ Time Frame: baseline to week 25 ] [ Designated as safety issue: No ]
  • Change in the NPI-Q; [ Time Frame: baseline to week 25 ] [ Designated as safety issue: No ]
  • Change on the IADL scale; [ Time Frame: baseline to week 25 ] [ Designated as safety issue: No ]
  • Patient's convenience questionnaire. [ Time Frame: baseline to week 25 ] [ Designated as safety issue: No ]

Enrollment: 128
Study Start Date: February 2007
Study Completion Date: September 2009
Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
ZT-1 (investigational product)
Drug: 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.
Active Comparator: 2
Donepezil
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.
Other Name: Aricept

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   50 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00423228

Locations
Australia, New South Wales
Central Coast Neuroscience Research
East Gosford, New South Wales, Australia, 2250
Hornsby-Kuring-gai Health Service
Hornsby, New South Wales, Australia, 2077
Southern Neurology
Kogarah, New South Wales, Australia, 2217
Australia, Queensland
The Prince Charles Hospital
Chermside, Queensland, Australia, 4032
Australia, South Australia
Royal Adelaide Hospital
Adelaïde, South Australia, Australia, 5000
The Queen Elizabeth Hospital
Woodville, South Australia, Australia, 5011
Australia, Victoria
St George's Hospital
Kew, Victoria, Australia, 3101
Austin Health Repatriation Hospital
West Heidelberg, Victoria, Australia, 3081
Australia, Western Australia
Hollywood Specialist Centre
Nedlands (Perth), Western Australia, Australia, 6009
Canada, Alberta
Calgary West Medical Centre
Calgary, Alberta, Canada, T3C 3P1
Castledowns Medicentre
Edmonton, Alberta, Canada
Saibal Nandy Professional Corporation
Medicine Hat, Alberta, Canada, T1A 4C2
Canada, Ontario
Parkwood Hospital
London, Ontario, Canada, N6C 5J1
Gerontion Research Inc.
Toronto, Ontario, Canada, M6M 3Z5
Toronto Memory Program
Toronto, Ontario, Canada, M3B 2W7
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, P.Q. H3T 1E2
Neuro Rive-Sud
Montreal, Quebec, Canada, J4V 2J2
Canada
The Medical Arts Health Research Group
Kelowna, Canada, V1Y 3G8
Douglas Hospital Research Center
Montréal, Canada, H4H 1R3
The Medical Arts Health Research Group
Penticton, Canada, V2A 5C8
United Kingdom
OPMHS
Crowborough, East Sussex, United Kingdom, TN61HB
Glasgow Memory Clinic
Glasgow, Scotland, United Kingdom, G20 0XA
Llandough Hospital
Penarth, Wales, United Kingdom, CF64 2XX
Royal Blackburn Hospital
Blackburn, United Kingdom, M8 5RB
Camden and Islington Mental Health Trust
London, United Kingdom, NW1 9DB
North Manchester General Hospital
Manchester, United Kingdom, M85RB
New Castle General Hospital
Newcastle upon Tyne, United Kingdom, NE4 6BE
MARC - Moorgreen Hospital
Southampton, United Kingdom, SO30 3JB
Sponsors and Collaborators
Debiopharm International SA
Investigators
Study Director: Emmanuel Tamches, MD Debiopharm SA
  More Information

Additional Information:
Publications:
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.

Responsible Party: Emmanuel Tamchès, M.D., Debiopharm S.A.
ClinicalTrials.gov Identifier: NCT00423228     History of Changes
Other Study ID Numbers: DEB-ZTSR-201, EUDRACT no. 2006-005161-18
Study First Received: January 17, 2007
Last Updated: August 9, 2011
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Debiopharm International SA:
Alzheimer's disease
cognitive impairment
cholinesterase inhibitors
sustained-release implants
long acting treatment

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Cholinesterase Inhibitors
Donepezil
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 17, 2014