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

Keywords

• Attention
• cancer
• chemotherapy
• donepezil
• acetylcholinesterase
• inhibitor

Lead sponsor

Eisai Inc. is the lead sponsor of 361 studies on the registry; 8 are open to participants now.

Of its 81 completed or terminated interventional studies of FDA-regulated products, 54 (67%) have results posted.

Eligibility criteria

Study arms

• Experimental
  1

  Drug: Donepezil hydrochloride

• Placebo comparator
  2

  Drug: Placebo

Interventions

• DrugDonepezil 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).

  Also known as: Aricept

• DrugPlacebo

  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).

Primary outcomes

1. 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.

   Time frame: Baseline and Week 12

Secondary outcomes

1. 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.

   Time frame: Baseline and Week 6

2. 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.

   Time frame: Baseline, Weeks 6 and 12

3. 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.

   Time frame: Baseline and Week 12

Baseline characteristics