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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/NCT00103948




Registration number
NCT00103948
Ethics application status
Date submitted
17/02/2005
Date registered
18/02/2005
Date last updated
3/11/2015

Titles & IDs
Public title
The Efficacy, Safety, And Tolerability Of Donepezil HCl (E2020) In Patients With CADASIL Who Have Cognitive Impairment
Scientific title
An 18-Week, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study Of The Efficacy, Safety, And Tolerability Of Donepezil HCl (E2020) In Patients With CADASIL Who Have Cognitive Impairment
Secondary ID [1] 0 0
2004-001162-40
Secondary ID [2] 0 0
E2020-A001-233
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cognitive Impairment 0 0
Condition category
Condition code
Neurological 0 0 0 0
Other neurological disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Mental Health 0 0 0 0
Other mental health disorders

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

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

Outcomes
Primary outcome [1] 0 0
Cognitive function.
Timepoint [1] 0 0

Eligibility
Key inclusion criteria
- Age range - Adult patients, 25 to 70 years of age inclusive

- Gender distribution - Men and women. -- Women of childbearing potential (<1 year
postmenopausal) must be practicing effective contraception and have a negative serum
bHCG at Screening. Pregnant and/or lactating females are excluded. Patients who become
pregnant during the study will be discontinued.

- Diagnostic evidence of CADASIL either by (1) identification of a NOTCH3 mutation
(excluding polymorphisms) or (2) presence of typical deposits on an electron
microscopy of a skin biopsy.

- Cognitive impairment - (1) Subjects or their study partners must give a description of
cognitive problems and one of the following: (2a) MMSE score of 10-27 (inclusive) or
(2b) Trails B score, 1.5 standard deviations below the mean after adjustment for age
and education.

- Head MRI - Evidence of disease consistent with CADASIL, and no evidence of another
disease, which might account for cognitive impairment or dementia (as judged by the
Investigator/physician at the site). (The latter may be determined with a CT head scan
for eligibility purposes. The MRI would still be needed.) Must be obtained within 6
months of the Screening/Baseline visit. If no such head MRI had been previously
obtained, a head MRI will be obtained as part of Screening/Baseline after all other
inclusion and exclusion criteria (except clinical laboratory determinations) are
satisfied. Patients in whom an MRI is contraindicated can have a CT instead, however,
MRI is the preferred modality.

- Race and ethnicity - Any race and ethnic group.

- Health - Generally healthy, ambulatory or ambulatory-aided (i.e., walker, cane or
wheelchair) outpatient. Speech, motor function, comprehension, and corrected vision
and hearing must be sufficient for compliance with all testing procedures.

- Clinical laboratory values must be within normal limits, or if abnormal, must be
judged clinically insignificant by the Investigator/ physician.

- Patients with Vitamin B12 deficiency who are on a stable dose of medication for at
least 12 weeks prior to Screening/Baseline and who have normal serum B12 levels at
Screening/ Baseline will be eligible. Patients who might otherwise have been eligible
can be re- screened when they meet this criterion. This stable dose of Vitamin B12
must be maintained throughout the study.

- Patients with hypothyroidism or hyperthyroidism who are on a stable dose of medication
for at least 12 weeks prior to Screening, have a normal TSH and free T4 at screening,
and are considered euthyroid will be eligible. Patients who might otherwise have been
eligible can be re-screened when they meet this criterion. This stable dose must be
maintained throughout the study.

- Patients must have a reliable study partner who has regular contact with the patient
(e.g., an average of 4 or more contacts per week), can observe for possible adverse
events, and can accompany the patient to all visits.

- Patients with a history of hypertension, cardiac disease, diabetes, or peripheral
vascular disease, may be enrolled in the study provided that the following standards
are met. -- Hypertension must be medication controlled (sitting SBP < 175, sitting DBP
< 100 mm Hg) and cardiac disease (e.g., angina pectoris, congestive heart failure,
right bundle branch block, or arrhythmias) is stable on appropriate medication for 12
weeks prior to Screening.

Peripheral vascular disease must have been stable for 12 weeks prior to Screening. No
elective surgical procedures should be planned during the course of the study (e.g., hernia
repair and bunion removal). Patient with diabetes must be stable as demonstrated by an
HbA1c of <= 8.0% or a random serum glucose value of <= 170 mg/dL.

- All patients with CADASIL are at risk for stroke/TIA and may be enrolled in the study
provided that no new strokes have been diagnosed or identified to have occurred within
the three months prior to Screening. Patients who might otherwise be eligible can be
screened 12 weeks after the stroke. Patients with TIAs are eligible without a waiting
period. Patients who are already enrolled will continue in the study as assessed by
the Investigator/ physician.

- Patients with CADASIL may suffer depression. Such patients are eligible for enrollment
if they are stable on medication for 12 weeks and have an MADRS score < 20. Patients
with an MADRS score >= 20 may be re-screened after 12 weeks on a stable dose of
medication. This stable dose must be maintained throughout the study.

- Minor medical conditions must be stable before study enrollment.

- Patients who are taking Gingko Biloba or Vitamin E and have been taking stable doses
of these compounds for 8 weeks are allowed in the study. This stable dose must be
maintained throughout the study.
Minimum age
25 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Neurological disorders affecting cognition or the ability to assess it that are not
associated with CADASIL, such as Alzheimer's Disease, Parkinson's disease, normal
pressure hydrocephalus, idiopathic seizure disorders, multiple sclerosis, cerebral
vasculitis or infections of the central nervous system, subdural hematoma, as well as
Human Immunodeficiency Virus (HIV) disease, a history of significant head trauma
followed by persistent neurological deficits, sleep disorders affecting level of
consciousness, or known structural brain abnormalities.

- Psychiatric disorders affecting the ability to assess cognition that are not typically
associated with CADASIL, such as schizophrenia.

- Active drug or alcohol abuse or dependence in <= 5 years by DSM-IV criteria.

- Any active or clinically significant conditions affecting absorption, distribution, or
metabolism of the study medication (e.g., inflammatory bowel disease, hepatic disease,
or severe lactose intolerance).

- Uncontrolled hypertension (sitting systolic >= 175 mmHg and/or diastolic >= 100 mmHg)
as assessed by the Investigator regardless of whether the patient is taking
antihypertensive medication.

- Evidence of clinically significant, active gastrointestinal, renal, hepatic,
respiratory, infectious, endocrine, or cardiovascular system disease. A patient so
excluded, who subsequently becomes stable for 4 weeks, may become eligible for
enrollment if Inclusion Criteria 2) and 3) are met.

- Patients with left bundle branch block are excluded.

- History of malignant neoplasms (does not include basal or squamous cell carcinoma of
the skin) treated within 2 years prior to study entry, current evidence of malignant
neoplasm, or recurrent or metastatic disease.

- Women who are pregnant or breastfeeding.

- Patients and/or study partners who are unwilling or unable to fulfill the requirements
of the study.

- Known hypersensitivity to cholinesterase inhibitors or piperidine-containing drug.

- Use of any unapproved prior or concomitant medications as defined in the protocol.

- Any condition that would make the patient or study partner, in the opinion of the
Investigator, unsuitable for the study.

- Involvement in any other investigational trial in the preceding 12 weeks or likely
involvement in any other investigational study drug trial during the course of this
study. Prior to enrollment, the study director or medical monitor must approve
involvement in investigational trials that do not involve a study drug.

- Patients with changes in doses of concomitant medication, not otherwise described,
within the 6 weeks prior to enrollment.

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?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
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
1/02/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/02/2007
Sample size
Target
Accrual to date
Final
165
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
- Woodville
Recruitment postcode(s) [1] 0 0
5011 - Woodville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Illinois
Country [2] 0 0
United States of America
State/province [2] 0 0
New York
Country [3] 0 0
Spain
State/province [3] 0 0
Malaga

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is an 18-week, prospective, multi-center, randomized, double-blind, placebo-controlled,
(1:1) parallel-group study.
Trial website
https://clinicaltrials.gov/ct2/show/NCT00103948
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Margaret Moline, Ph.D.
Address 0 0
Eisai Inc.
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