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

Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety of Donepezil Hydrochloride in Preadolescent and Adolescent Children With Attention Impairment Following Cancer Treatment

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.

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.

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.