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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00423228




Registration number
NCT00423228
Ethics application status
Date submitted
17/01/2007
Date registered
18/01/2007
Date last updated
14/01/2015

Titles & IDs
Public title
Efficacy Study of a ZT-1 Implant in Patients Suffering From Alzheimer's Disease
Scientific 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
Secondary ID [1] 0 0
EUDRACT no. 2006-005161-18
Secondary ID [2] 0 0
DEB-ZTSR-201
Universal Trial Number (UTN)
Trial acronym
BRAINz
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Moderate Alzheimer's Disease 0 0
Condition category
Condition code
Neurological 0 0 0 0
Alzheimer's disease
Neurological 0 0 0 0
Dementias

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ZT-1
Treatment: Drugs - Donepezil

Experimental: ZT-1 - ZT-1 (investigational product)

Active Comparator: Donepezil - Donepezil


Treatment: Drugs: 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.

Treatment: Drugs: 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 code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Change in the MMSE score from baseline to week 25
Timepoint [1] 0 0
baseline to week 25
Secondary outcome [1] 0 0
Responder rate as defined by at least 2 points improvement in the MMSE score;
Timepoint [1] 0 0
baseline to week 25
Secondary outcome [2] 0 0
Change on the ADAS-Cog 11 items subscale;
Timepoint [2] 0 0
baseline to week 25
Secondary outcome [3] 0 0
Change in the NPI-Q;
Timepoint [3] 0 0
baseline to week 25
Secondary outcome [4] 0 0
Change on the IADL scale;
Timepoint [4] 0 0
baseline to week 25
Secondary outcome [5] 0 0
Patient's convenience questionnaire.
Timepoint [5] 0 0
baseline to week 25

Eligibility
Key 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.
Minimum age
50 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2007
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2009
Sample size
Target
Accrual to date
Final
228
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Central Coast Neuroscience Research - East Gosford
Recruitment hospital [2] 0 0
Hornsby-Kuring-gai Health Service - Hornsby
Recruitment hospital [3] 0 0
Southern Neurology - Kogarah
Recruitment hospital [4] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [5] 0 0
Royal Adelaide Hospital - Adelaïde
Recruitment hospital [6] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [7] 0 0
St George's Hospital - Kew
Recruitment hospital [8] 0 0
Austin Health Repatriation Hospital - West Heidelberg
Recruitment hospital [9] 0 0
Hollywood Specialist Centre - Nedlands (Perth)
Recruitment postcode(s) [1] 0 0
2250 - East Gosford
Recruitment postcode(s) [2] 0 0
2077 - Hornsby
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
Recruitment postcode(s) [4] 0 0
4032 - Chermside
Recruitment postcode(s) [5] 0 0
5000 - Adelaïde
Recruitment postcode(s) [6] 0 0
5011 - Woodville
Recruitment postcode(s) [7] 0 0
3101 - Kew
Recruitment postcode(s) [8] 0 0
3081 - West Heidelberg
Recruitment postcode(s) [9] 0 0
6009 - Nedlands (Perth)
Recruitment outside Australia
Country [1] 0 0
Canada
State/province [1] 0 0
Alberta
Country [2] 0 0
Canada
State/province [2] 0 0
Ontario
Country [3] 0 0
Canada
State/province [3] 0 0
Quebec
Country [4] 0 0
Canada
State/province [4] 0 0
Kelowna
Country [5] 0 0
Canada
State/province [5] 0 0
Montréal
Country [6] 0 0
Canada
State/province [6] 0 0
Penticton
Country [7] 0 0
United Kingdom
State/province [7] 0 0
East Sussex
Country [8] 0 0
United Kingdom
State/province [8] 0 0
Scotland
Country [9] 0 0
United Kingdom
State/province [9] 0 0
Wales
Country [10] 0 0
United Kingdom
State/province [10] 0 0
Blackburn
Country [11] 0 0
United Kingdom
State/province [11] 0 0
London
Country [12] 0 0
United Kingdom
State/province [12] 0 0
Manchester
Country [13] 0 0
United Kingdom
State/province [13] 0 0
Newcastle upon Tyne
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Southampton

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Debiopharm International SA
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00423228
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Emmanuel Tamches, MD
Address 0 0
Debiopharm SA
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00423228