Efficacy and Safety of Donepezil Hydrochloride in Preadolescent and Adolescent Children With Attention Impairment Following Cancer Treatment
Condition: Attention Impairment
Intervention: Donepezil hydrochloride; Placebo
Intervention description: 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).; 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 MeSH terms: Donepezil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 72.0
Sex: All
Minimum age: 6 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Attention; cancer; chemotherapy; donepezil; acetylcholinesterase; inhibitor

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.
    

Eligibility 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.

        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.