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

January 13, 2015 updated by: Debiopharm International SA

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

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.

Study Overview

Status

Completed

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

228

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

48 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: ZT-1
ZT-1 (investigational product)
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: 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 Names:
  • Aricept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Change in the MMSE score from baseline to week 25
Time Frame: baseline to week 25
baseline to week 25

Secondary Outcome Measures

Outcome Measure
Time Frame
Responder rate as defined by at least 2 points improvement in the MMSE score;
Time Frame: baseline to week 25
baseline to week 25
Change on the ADAS-Cog 11 items subscale;
Time Frame: baseline to week 25
baseline to week 25
Change in the NPI-Q;
Time Frame: baseline to week 25
baseline to week 25
Change on the IADL scale;
Time Frame: baseline to week 25
baseline to week 25
Patient's convenience questionnaire.
Time Frame: baseline to week 25
baseline to week 25

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Study Director: Emmanuel Tamches, MD, Debiopharm SA

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2007

Primary Completion (Actual)

April 1, 2009

Study Completion (Actual)

April 1, 2009

Study Registration Dates

First Submitted

January 17, 2007

First Submitted That Met QC Criteria

January 17, 2007

First Posted (Estimate)

January 18, 2007

Study Record Updates

Last Update Posted (Estimate)

January 14, 2015

Last Update Submitted That Met QC Criteria

January 13, 2015

Last Verified

January 1, 2015

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Moderate Alzheimer's Disease

Clinical Trials on ZT-1

3
Subscribe