Efficacy and Safety of Donepezil Hydrochloride in Preadolescent and Adolescent Children With Attention Impairment Following Cancer Treatment

Phase 3

Completed

• Conditions: Attention Impairment
• Interventions: Drug: Donepezil hydrochloride; Drug: Placebo

• Registration Number: NCT00688376
• Lead Sponsor: Eisai Inc.

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.

Detailed Description

This is a double-blind, placebo-controlled, parallel group study in pediatric subjects who have persistent attention impairment following treatment for cancer. This trial has three phases: (1) pre-randomization to establish eligibility, (2) a 12-week, double-blind, placebo-controlled, parallel-group phase with dose escalation based on body weight, (3) a 12-week, blinded extension phase during which all subjects will receive active drug.

Study Timeline

• Study First Submitted: 2008-05-28
• Study First Submitted QC: 2008-05-30
• Study First Posted: 2008-06-02
• Study Start: 2008-07-02
• Primary Completion: 2009-05-26
• Study Completion: 2009-05-26
• Results First Submitted: 2011-07-21
• Status Verified: 2015-11
• Results First Submitted QC: 2020-03-16
• Results First Posted: 2020-03-27
• Last Update Submitted: 2021-12-14
• Last Update Posted: 2022-01-05

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 72

Inclusion Criteria

Not provided

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Donepezil hydrochloride	-
2	Placebo	-

Primary Outcome Measures

Name	Time	Method
Change From Baseline in the Test of Variables in Attention-Continuous Performance Test (TOVA-CPT) "D-prime" Standard Score (SS) at Week 12	Baseline and 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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in the TOVA-CPT "D-prime" Standard Score (SS) at Week 6	Baseline and 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.
Change From Baseline in the Reaction Time Variability Standard Score (RTVSS) and Response Time Standard Score (RTSS) at Weeks 6 and 12	Baseline, 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.
Change From Baseline in the Global Executive Composite Score, Behavioral Regulation Index, Metacognition Index, and Working Memory Subscale	Baseline and Week 12	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.

Trial Locations

Locations (1)

Road Runner Research Ltd.; 🇺🇸 San Antonio, Texas, United States