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

NCT00688376 | Completed Phase 3 Results

• 3 other identifiers: E2020-G000-333E2020-G000-3342007-005435-28
• Study Type: interventional
• Target: 72
• Locations: 10 countries
• Sites: 31

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.

Conditions

Attention Impairment

Keywords

Attention; cancer; chemotherapy; donepezil; acetylcholinesterase; inhibitor

Outcome Measures

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.

  Baseline and Week 12

Secondary Outcomes (3)

• Change From Baseline in the TOVA-CPT "D-prime" Standard Score (SS) at Week 6

  Baseline and Week 6

• 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

• Change From Baseline in the Global Executive Composite Score, Behavioral Regulation Index, Metacognition Index, and Working Memory Subscale

  Baseline and Week 12

Study Arms (2)

1

EXPERIMENTAL

Drug: Donepezil hydrochloride

2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Donepezil hydrochloride DRUG

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

1

Placebo DRUG

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).

2

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from the study:
• Inability to perform the required tests (for example, because of aphasia, motor deficits affecting the dominant hand, or mental retardation).
• Motor coordination not sufficient, according to tests to be conducted at the time of screening.
• Recurrence of cancer. If this happens, the subject will have to withdraw from the study.
• Mental retardation/developmental disability.
• Certain medications, such as methylphenidate, are not allowed during the study.
• Major depression.
• Problems with the digestive tract that could affect the subject's ability to absorb the study drug.
• Hypersensitivity to a chemical class known as piperidine derivatives.
• Certain other medical conditions as determined by clinical staff.
• Alcoholism, drug abuse, or organic brain disease other than that caused by the cancer or its treatment.
• Pregnancy, nursing, or unwillingness to undergo pregnancy testing if requested by clinical staff.
• 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.
• If sexually active, unwillingness to use birth control (males and females).
• Plans for certain types of elective surgery that would occur while the study is in progress.

Sponsors & Collaborators

• Eisai Inc.: lead
• Eisai Limited: collaborator

Study Sites (31)

Unknown Facility

Stanford, California, 94305-5826, United States

Location

Unknown Facility

Miami, Florida, 33155, United States

Location

Unknown Facility

Minneapolis, Minnesota, 55404, United States

Location

Unknown Facility

St Louis, Missouri, 63110, United States

Location

Unknown Facility

New Brunswick, New Jersey, 08903, United States

Location

Unknown Facility

Brooklyn, New York, 11209, United States

Location

Unknown Facility

Great Neck, New York, 10021, United States

Location

Unknown Facility

New York, New York, 10065, United States

Location

Unknown Facility

Chapel Hill, North Carolina, 27514, United States

Location

Unknown Facility

Oklahoma City, Oklahoma, 73104, United States

Location

Unknown Facility

Dallas, Texas, 75235, United States

Location

Unknown Facility

Houston, Texas, 77030, United States

Location

Road Runner Research Ltd.

San Antonio, Texas, 78258, United States

Location

Unknown Facility

Cordoba Capital, Córdoba Province, 5000, Argentina

Location

Unknown Facility

Buenos Aires, C1181ACH, Argentina

Location

Unknown Facility

Buenos Aires, C1428AQK, Argentina

Location

Unknown Facility

Sydney, New South Wales, 2301, Australia

Location

Unknown Facility

Westmead, Sydney, New South Wales, 2045, Australia

Location

Unknown Facility

Calgary, Alberta, T2T5C7, Canada

Location

Unknown Facility

Antonio Varas, Providencia Santiago, 360, Chile

Location

Unknown Facility

Santa María, Providencia Santiago, 0410, Chile

Location

Unknown Facility

Vandoeurvre Les Nancy, 54511, France

Location

Unknown Facility

Villejuif, 94805, France

Location

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Cologne, 50924, Germany

Location

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Amsterdam, 1081 HV, Netherlands

Location

Unknown Facility

Groningen, 9713 GZ, Netherlands

Location

Unknown Facility

Rotterdam, 3015 GJ, Netherlands

Location

Unknown Facility

Utrecht, 3584 EA, Netherlands

Location

Unknown Facility

Palma de Mallorca, 07198, Spain

Location

Unknown Facility

Valencia, 46009, Spain

Location

Unknown Facility

Sutton, Surrey, SM2 5PT, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Pain

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data.

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2008
• First Posted: June 2, 2008
• Study Start: July 2, 2008
• Primary Completion: May 26, 2009
• Study Completion: May 26, 2009
• Last Updated: January 5, 2022
• Results First Posted: March 27, 2020

Record last verified: 2015-11

Locations

AU (2); AR (3); FR (2); NL (4); ES (2); GB (1); US (13); CA (1); DE (1); CL (2)