Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (Aricept) In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome, Aged 6 To 10
Condition: Down Syndrome; Cognitive Dysfunction
MeSH terms: Down Syndrome; Syndrome; Cognitive Dysfunction
Intervention: Aricept (Donepezil hydrochloride); Placebo
Intervention description: All subjects will start with a dose of 1.25 mg/day (1.25 ml) donepezil ; dose escalations will occur every 2 weeks to a maximum of 5 mg/day (5 ml) donepezil.
All doses will be administered orally.; All subjects will start with a dose of 1.25 mg/day (1.25 ml) placebo; dose escalations will occur every 2 weeks to a maximum of 5 mg/day (5 ml) placebo.
All doses will be administered orally.
Intervention MeSH terms: Donepezil
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 9.0
Sex: All
Minimum age: 6 Years
Maximum age: 10 Years
Healthy volunteers: No
Keywords: pediatric; Down syndrome; cognitive dysfunction; Downs; Aricept; children with Down syndrome

Summary:

      The purpose of this study is to determine the efficacy and safety of donepezil hydrochloride
      (Aricept) in the treatment of cognitive dysfunction shown by children with Down syndrome,
      aged 6 to 10 years.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age range: Subjects 6 to 10 years of age at the screening visit; weight >= 15 kg.

          -  Sex distribution: both males and females.

          -  VABS-II/PCRF receptive sub-domain raw score of >= 25 and expressive sub-domain raw
             score of >= 61.

          -  Clinical diagnosis of Down syndrome (DS) - subjects may have free trisomy 21,
             Robertsonian translocations, or mosaic DS

          -  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 patient in the study. The exception
             to this prior use is that subjects who participated in the Phase II study
             E2020-A001-219 (A2501059) are not eligible.

          -  Subjects residing in the community or in facilities that have consistent and reliable
             caregivers who can provide efficacy information about the subjects.

          -  The subjects must be expected to complete all procedures scheduled during the
             Screening and Baseline visits including all efficacy and safety parameters. Subjects
             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.

          -  Subjects must have a parent, or other reliable caregiver who agrees to accompany the
             subject to all clinic visits, provide information about the subject as required by the
             protocol, and ensure compliance with the medication schedule.

          -  The parent or caregiver must be a constant and reliable informant with sufficient
             contact with the subject to have detailed knowledge of the subject'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.

          -  Subjects should be in good general health with no medical conditions that are
             considered both clinically significant and unstable.

          -  Clinical laboratory values within normal limits or abnormalities considered not
             clinically significant by the investigator and sponsor.

          -  Subjects 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.)

          -  Subjects 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.

          -  Subjects 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.

          -  Subjects 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.

        Exclusion Criteria:

          -  Age range: Subjects <6 or >10 years at the screening visit.

          -  Subjects 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.

          -  Subjects with a known hypersensitivity to piperidine derivatives or cholinesterase
             inhibitors.

          -  Subjects 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 subject in this
             study. Also excluded are subjects who participated in the Phase II study
             E2020-A001-219 (A2501059). In addition, subjects may not have taken any other
             investigational medications (including memantine) within 3 months prior to screening.

          -  Subjects 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.

          -  Subjects with clinically significant obstructive pulmonary disease or asthma,
             untreated or not controlled by treatment within 3 months prior to screening.

          -  Subjects with recent (<= 1 year) or ongoing hematologic/oncologic disorders (mild
             anemia allowed).

          -  Evidence of active, clinically significant, and unstable gastrointestinal, renal,
             hepatic, endocrine or cardiovascular system disease.

          -  Subjects 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.

          -  Any condition which would make the patient or the caregiver, in the opinion of the
             investigator, unsuitable for the study.