Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (Aricept) In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome, Aged 11 To 17

The study will be conducted in approximately 75 sites in the US, India, Singapore, South
Korea, Mexico and Chile and will include 210 participants to be enrolled.

Inclusion Criteria:

1. Age range: Participants 11 to 17 years of age at the screening visit; weight >35
kilograms (kg).

2. Sex distribution: both males and females.

3. Vineland-II Adaptive Behavior Scales (VABS-II)/Parent/Caregiver Rating Form (PCRF)
receptive sub-domain raw score of >= 25 and expressive sub-domain raw score of >= 61.

4. Clinical diagnosis of Down syndrome (DS) - participants may have free trisomy 21,
Robertsonian translocations, or mosaic DS.

5. Naive to approved or unapproved cholinesterase inhibitors (Aricept, Exelon, Cognex,
Reminyl/Razadyne, metrifonate, physostigmine) is preferred. However, prior use of
these medications is allowed, provided that the medication was discontinued at least 3
months prior to screening and that it was not discontinued for lack of tolerability or
efficacy or for the sole purpose of enrolling the participant in the study. The
exception to this prior use is that participants who participated in the Phase II
study E2020-A001-219 (A2501059) are not eligible.

6. Participants residing in the community or in facilities that have consistent and
reliable caregivers who can provide efficacy information about the participants.

7. The participants must be expected to complete all procedures scheduled during the
Screening and Baseline visits including all efficacy and safety parameters.
Participants who are verbal and able to be understood most of the time are preferred,
but those who use other forms of communication, signs, symbol boards or devices to
supplement his/her communication ability may be enrolled provided they meet the
VABS-II/PCRF receptive and expressive score criteria mentioned above.

8. Participants must have a parent, or other reliable caregiver who agrees to accompany
the participant to all clinic visits, provide information about the participant as
required by the protocol, and ensure compliance with the medication schedule.

9. The parent or caregiver must be a constant and reliable informant with sufficient
contact with the participant to have detailed knowledge of the participant's adaptive
functioning in order to be able to complete the VABS-II/PCRF accurately. The same
individual should complete the form at every visit, if possible.

10. Participants should be in good general health with no medical conditions that are
considered both clinically significant and unstable.

11. Clinical laboratory values within normal limits or abnormalities considered not
clinically significant by the investigator and sponsor.

12. Participants with stable Type I (insulin-dependent) or Type II diabetes are eligible
provided they are monitored regularly prior to and during the study to ensure adequate
glucose control. (Adequacy of control is based on the investigator's judgment, but
should be guided primarily by a glycosylated hemoglobin [hemoglobin A1c] <8.0 at
screening; other information, including records of home monitoring and the screening
fasting glucose may support this judgment).

13. Participants with thyroid disease also may be included in the study provided they are
euthyroid and stable on treatment for at least 1 month prior to screening.

14. Participants with a history of seizure disorder are allowed provided that they are on
stable treatment for at least 3 months and have not had a seizure within the past 6
months.

15. Participants should be independent in ambulation or ambulatory aided (i.e., walker or
cane, to wheelchair); vision and hearing (eyeglasses and/or hearing aid permissible)
sufficient for achieving VABS-II/PCRF minimum receptive raw scores of >= 25 and
expressive scores of >= 61 and for cooperating with secondary efficacy evaluations and
study examinations.

16. Females who have begun menstruation and are thus of child-bearing potential may be
enrolled but must be documented not to be pregnant by serum pregnancy testing at
screening. They also must be practicing an effective means of birth control
(abstinence, oral contraceptives, hormonal implants in place at least 1 month prior to
enrollment, or a double-barrier method), which must be documented, and the participant
and caregiver must be counseled in writing of the importance of not becoming pregnant
during the trial. A urine pregnancy test will be done at the Week 4 clinic visit and
must be negative prior to dispensing any medication; a serum pregnancy test will be
repeated at the Week 10 (or Early Termination) clinic visit.

Exclusion Criteria:

1. Age range: Participants <11 or >17 years at the screening visit.

2. Participants with active or clinically significant conditions that will, in the
investigator's judgment, affect absorption, distribution or metabolism of the study
medication (e.g., inflammatory bowel disease, gastric or duodenal ulcers or severe
lactose intolerance); controlled celiac disease is allowed.

3. Participants with a known hypersensitivity to piperidine derivatives or cholinesterase
inhibitors.

4. Participants currently receiving cholinesterase inhibitors or who have received them
in the 3 months prior to screening or with prior use >3 months prior to screening who
stopped for lack of efficacy or tolerability or simply to enroll the participant in
this study. Also excluded are participants who participated in the Phase II study
E2020-A001-219 (A2501059). In addition, participants may not have taken any other
investigational medications (including memantine) within 3 months prior to screening.

5. Participants without a reliable parent or caregiver (caregiver responsibilities are
described in the Inclusion Criteria above), or with parents or caregivers who are
unwilling or unable to complete any of the outcome measures and fulfill the
requirements of this study.

6. Participants with clinically significant obstructive pulmonary disease or asthma,
untreated or not controlled by treatment within 3 months prior to screening.

7. Participants with recent (<= 1 year) or ongoing hematologic/oncologic disorders (mild
anemia allowed).

8. Evidence of active, clinically significant, and unstable gastrointestinal, renal,
hepatic, endocrine or cardiovascular system disease.

9. Participants with a current Diagnostic and Statistical Manual of Mental Disorders
(DSM-IV) diagnosis of Major Depressive Disorder (MDD) or any current primary
psychiatric diagnosis other than DS (as per DSM-IV). Diagnoses that are secondary,
such as attention deficit hyperactivity disorder, are allowed.

10. Any condition which would make the patient or the caregiver, in the opinion of the
investigator, unsuitable for the study. Unsuitability includes female participants who
have begun menstruation and are thus of child-bearing potential, and who are not
practicing an effective means of birth control. Female participants who have begun
menstruation and are sexually abstinent or who are practicing another effective means
of birth control are not excluded but must be counseled in writing along with their
caregiver about the importance of not becoming pregnant during the study and must have
a negative pregnancy test at screening and pregnancy testing at Weeks 4 and 10.