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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00688376




Registration number
NCT00688376
Ethics application status
Date submitted
28/05/2008
Date registered
2/06/2008
Date last updated
27/03/2020

Titles & IDs
Public title
Efficacy and Safety of Donepezil Hydrochloride in Preadolescent and Adolescent Children With Attention Impairment Following Cancer Treatment
Scientific title
Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety of Donepezil Hydrochloride in Preadolescent and Adolescent Children With Attention Impairment Following Cancer Treatment
Secondary ID [1] 0 0
E2020-G000-334
Secondary ID [2] 0 0
E2020-G000-333
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Attention Impairment 0 0
Condition category
Condition code

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

Experimental: 1 -

Placebo Comparator: 2 -


Treatment: Drugs: Donepezil hydrochloride
During the 12-week Double-Blind Phase, subjects will receive oral donepezil hydrochloride tablets starting at a dose of 3 mg once daily. Doses will be increased incrementally at successive 3-week intervals on the basis of weight and tolerability. The final daily dose will be 3, 5, or 10 mg depending on body weight.
During the Blinded Extension Phase, all subjects will receive active treatment (donepezil).

Treatment: Drugs: Placebo
During the 12-week Double-Blind Phase, subjects will receive matching placebo tablets (3, 5, of 10 mg) once daily.
During the 12-week Blinded Extension Phase, all subjects will receive active treatment (donepezil).

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

Outcomes
Primary outcome [1] 0 0
Change From Baseline in the Test of Variables in Attention-Continuous Performance Test (TOVA-CPT) "D-prime" Standard Score (SS) at Week 12 - TOVA-CPT test has a standardized computer game-like format that tests attention and simple impulse control. It precisely measures a person's reaction time to clicking on correct targets versus incorrect targets. Scores are based on the number of "Hits" (correct responses), omission errors (failure to respond), commission errors/"False Alarms" (incorrect responses), response time, and sensitivity ("d-prime"). "D-prime" a dimensionless statistics is a measure of distractibility and reflects how well a person reacts correctly versus incorrectly. A higher value of "d-prime" is reached by having more "Hits" (correct response) and fewer "False Alarms" (incorrect response). Analysis was based on three factors: the "d-prime" standard score, reaction time variability standard score, and response time standard score. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.
Timepoint [1] 0 0
Baseline and Week 12
Secondary outcome [1] 0 0
Change From Baseline in the TOVA-CPT "D-prime" Standard Score (SS) at Week 6 - TOVA-CPT test has a standardized computer game-like format that tests attention and simple impulse control. It precisely measures a person's reaction time to clicking on correct targets versus incorrect targets. Scores are based on the number of "Hits" (correct responses), omission errors (failure to respond), commission errors/"False Alarms" (incorrect responses), response time, and sensitivity ("d-prime"). "D-prime" a dimensionless statistics is a measure of distractibility and reflects how well a person reacts correctly versus incorrectly. A higher value of "d-prime" is reached by having more "Hits" (correct response) and fewer "False Alarms" (incorrect response). Analysis was based on three factors: the "d-prime" standard score, reaction time variability standard score, and response time standard score. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.
Timepoint [1] 0 0
Baseline and Week 6
Secondary outcome [2] 0 0
Change From Baseline in the Reaction Time Variability Standard Score (RTVSS) and Response Time Standard Score (RTSS) at Weeks 6 and 12 - The Reaction Time Variability is defined as the time measurement of how consistently the switch is pressed. The Response Time is the measurement of how fast or slow information is processed and responded to by the participant. The testing process was as described in a previous outcome measure. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.
Timepoint [2] 0 0
Baseline, Weeks 6 and 12
Secondary outcome [3] 0 0
Change From Baseline in the Global Executive Composite Score, Behavioral Regulation Index, Metacognition Index, and Working Memory Subscale - Behavioral Rating Inventory of Executive Functioning test evaluates impairment of executive function(planning and organization),memory,and sustained attention in children aged 5-18 years with wide range of developmental and acquired neurological conditions.Survey assess parent/guardian's perception of their child's executive functioning in home and school environments,which relate to daily function(as judged by parent).Each survey contains 86 items scored as;1(behavior is never a problem),2(behavior is sometimes a problem),or 3(behavior is often a problem).Data was presented as t-scores(raw scale scores are used to generate t-scores)for Global Executive Composite Score(t-score range 72-216),Behavioral Regulation Index(t-score range 28-84;inhibit,shift,and emotional control),Metacognition Inde (t-score range 44-132;initiate,working memory,plan/organize,organization of materials, and monitor),and Working Memory Subscale(t-score range 35-90).Higher scores indicate decline in performance.
Timepoint [3] 0 0
Baseline and Week 12

Eligibility
Key inclusion criteria
1. The subject must have received at least one cycle of chemotherapy and/or cranial
radiation, and must have completed this treatment at least one year before screening
takes place for entry into this study.

2. Subjects may be male or female; age range: 6 - 17.5 years; weight = 20 kg. They must
be physically healthy and able to move about, with or without aids, must be living in
the community, and must have adequate motor skills as shown by tests that will be
given at the time of screening. The subject's eyesight and hearing must be good enough
to allow cooperation with tests and physical examinations. Additionally, they must be
able to swallow tablets.

3. There must be subjective complaints by subject and/or parent of difficulties in school
or other daily activities, possibly related to impairments in attention. These
difficulties must have emerged after treatment for cancer and must still be present 12
months after cessation of treatment. There must also be objective evidence for this
impairment, as shown by a test that will be given to the subject at the time of
screening.

4. The IQ must be >70 according to tests that will be given at the time of screening.

5. The first language in which the subject learned to read and write must be one that
uses Roman lettering (a, b, c, etc.) and Arabic numerals (1, 2, 3, etc.).

6. The subject must not have previously taken any drugs in the class known as
cholinesterase inhibitors.

7. A parent or legal guardian must be available who is willing and able to complete all
of the outcome measures, to administer medications, and to accompany the subject to
the required clinic visits.

8. Subjects with diabetes or thyroid disease may still be eligible if certain medical
requirements are satisfied.

9. Female subjects who could become pregnant must undergo pregnancy testing and must
agree to use contraception.
Minimum age
6 Years
Maximum age
17 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Subjects who meet any of the following criteria will be excluded from the study:

1. Inability to perform the required tests (for example, because of aphasia, motor
deficits affecting the dominant hand, or mental retardation).

2. Motor coordination not sufficient, according to tests to be conducted at the time of
screening.

3. Recurrence of cancer. If this happens, the subject will have to withdraw from the
study.

4. Mental retardation/developmental disability.

5. Certain medications, such as methylphenidate, are not allowed during the study.

6. Major depression.

7. Problems with the digestive tract that could affect the subject's ability to absorb
the study drug.

8. Hypersensitivity to a chemical class known as piperidine derivatives.

9. Certain other medical conditions as determined by clinical staff.

10. Alcoholism, drug abuse, or organic brain disease other than that caused by the cancer
or its treatment.

11. Pregnancy, nursing, or unwillingness to undergo pregnancy testing if requested by
clinical staff.

12. Pregnancy, lactation or plans to become pregnant, or unwilling to take a screening
Beta-human chorionic gonadotropin (ßhCG) test if a female >10 years of age.

13. If sexually active, unwillingness to use birth control (males and females).

14. Plans for certain types of elective surgery that would occur while the study is in
progress.

15. Plans for travel or other events that would interfere with the study schedule.

16. Active treatment with another investigational drug within 3 months of the screening
visit.

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 analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
- Sydney
Recruitment hospital [2] 0 0
- Westmead, Sydney
Recruitment postcode(s) [1] 0 0
2301 - Sydney
Recruitment postcode(s) [2] 0 0
2045 - Westmead, Sydney
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Minnesota
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Oklahoma
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Argentina
State/province [10] 0 0
Provincia De Cordoba
Country [11] 0 0
Argentina
State/province [11] 0 0
Buenos Aires
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Chile
State/province [13] 0 0
Providencia Santiago
Country [14] 0 0
France
State/province [14] 0 0
Vandoeurvre Les Nancy
Country [15] 0 0
France
State/province [15] 0 0
Villejuif
Country [16] 0 0
Germany
State/province [16] 0 0
Koeln
Country [17] 0 0
Netherlands
State/province [17] 0 0
Amsterdam
Country [18] 0 0
Netherlands
State/province [18] 0 0
Groningen
Country [19] 0 0
Netherlands
State/province [19] 0 0
Rotterdam
Country [20] 0 0
Netherlands
State/province [20] 0 0
Utrecht
Country [21] 0 0
Spain
State/province [21] 0 0
Palma de Mallorca
Country [22] 0 0
Spain
State/province [22] 0 0
Valencia
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Surrey

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Eisai Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Eisai Limited
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate the efficacy, safety and tolerability of donepezil
in children with persistent attention impairment that is present at least 12 months after the
completion of cancer treatment.
Trial website
https://clinicaltrials.gov/show/NCT00688376
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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
Other publications