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

Moderate Alzheimer's Disease Clinical Trial

— BRAINz  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00423228
• Other study ID #: DEB-ZTSR-201
• Secondary ID: EUDRACT no. 2006
• Status: Completed
• Phase: N/A
• First received: January 17, 2007
• Last updated: January 13, 2015
• Start date: February 2007
• Est. completion date: April 2009

Study information

• Verified date: January 2015
• Source: Debiopharm International SA
• Contact: n/a
• Is FDA regulated: No
• Health authority: Australia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 228
• Est. completion date: April 2009
• Est. primary completion date: April 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Alzheimer Disease
• Moderate Alzheimer's Disease

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaïde	South Australia
Australia	The Prince Charles Hospital	Chermside	Queensland
Australia	Central Coast Neuroscience Research	East Gosford	New South Wales
Australia	Hornsby-Kuring-gai Health Service	Hornsby	New South Wales
Australia	St George's Hospital	Kew	Victoria
Australia	Southern Neurology	Kogarah	New South Wales
Australia	Hollywood Specialist Centre	Nedlands (Perth)	Western Australia
Australia	Austin Health Repatriation Hospital	West Heidelberg	Victoria
Australia	The Queen Elizabeth Hospital	Woodville	South Australia
Canada	Calgary West Medical Centre	Calgary	Alberta
Canada	Castledowns Medicentre	Edmonton	Alberta
Canada	The Medical Arts Health Research Group	Kelowna
Canada	Parkwood Hospital	London	Ontario
Canada	Saibal Nandy Professional Corporation	Medicine Hat	Alberta
Canada	Jewish General Hospital	Montreal	Quebec
Canada	Neuro Rive-Sud	Montreal	Quebec
Canada	Douglas Hospital Research Center	Montréal
Canada	The Medical Arts Health Research Group	Penticton
Canada	Gerontion Research Inc.	Toronto	Ontario
Canada	Toronto Memory Program	Toronto	Ontario
United Kingdom	Royal Blackburn Hospital	Blackburn
United Kingdom	OPMHS	Crowborough	East Sussex
United Kingdom	Glasgow Memory Clinic	Glasgow	Scotland
United Kingdom	Camden and Islington Mental Health Trust	London
United Kingdom	North Manchester General Hospital	Manchester
United Kingdom	New Castle General Hospital	Newcastle upon Tyne
United Kingdom	Llandough Hospital	Penarth	Wales
United Kingdom	MARC - Moorgreen Hospital	Southampton

Sponsors (1)

Lead Sponsor	Collaborator
Debiopharm International SA

Countries where clinical trial is conducted

Australia,  Canada,  United Kingdom, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the MMSE score from baseline to week 25		baseline to week 25	No
Secondary	Responder rate as defined by at least 2 points improvement in the MMSE score;		baseline to week 25	No
Secondary	Change on the ADAS-Cog 11 items subscale;		baseline to week 25	No
Secondary	Change in the NPI-Q;		baseline to week 25	No
Secondary	Change on the IADL scale;		baseline to week 25	No
Secondary	Patient's convenience questionnaire.		baseline to week 25	No

External Links

•   Sponsor of the Study