Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome
Condition: Down Syndrome
MeSH terms: Down Syndrome; Syndrome; Cognitive Dysfunction
Intervention: Donepezil HCl; Placebo
Intervention description: Blinded donepezil 2.5 milligram per day (mg/day) (2.5 milliliter per day [mL/day]) orally for participants with body weight (BW) 20 and less than (<) 25 kilogram (kg), 5 mg/day (5 mL/day) orally for participants with BW 25 to <50 kg, and 10 mg/day (10 mL/day) orally for participants with BW greater than or equal to (>=) 50 kg liquid formulation (1 milligram per 1 milliliter [1 mg/1 mL]) (titrated to 0.1 to 0.2 milligram per kilogram per day [mg/kg/day] based on BW).; Liquid formulation matched to active treatment for oral administration.
Intervention MeSH terms: Donepezil
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 129.0
Sex: All
Minimum age: 10 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Down Syndrome; trisomy 21

Summary:

      The purpose of this study is to determine whether donepezil HCl is effective and safe in
      improving cognitive dysfunction exhibited by children and adolescents with Down syndrome
      (DS). Effectiveness will be measured by rating communication, daily living skills, and social
      skills and relationships in subjects aged 10 to 17.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Ages 10 to 17 years old, weight more than or equal to 20 kg

          -  Male and female

          -  Vineland-II Adaptive Behavior Scales (VABS-II)/Parent/Caregiver Rating Form (PCRF)
             standard composite score greater than (>) 55

          -  Diagnosis of DS (trisomy 21) documented by chromosomal analysis (karyotyping). If such
             documentation is not available at screening, karyotyping will be performed with the
             screening labs and must be documented prior to baseline visit.

          -  Naïve to approved or unapproved cholinesterase inhibitors 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 subject in the
             study.

          -  Subjects residing in the community

          -  Must be expected to complete all procedures scheduled during the Screening and
             Baseline visits including all efficacy and safety parameters.

          -  Must speak English and be verbal and able to be understood most of the time and must
             not use other forms of communication, signs, symbol boards or devices to supplement
             his/her communication ability

          -  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

          -  a 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 behavior
             in order to be able to complete the VABS-II/PCRF accurately. The same individual
             should complete the form at every visit.

          -  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

          -  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
             (fasting blood glucose <140 milligram per deciliter (mg/dl) and glycosylated
             hemoglobin [hemoglobin A1c] <8 percent (%) at screening).

          -  Thyroid disease also may be included in the study provided they are euthyroid and
             stable on treatment for at least 3 months prior to screening.

          -  History of seizure disorder is allowed provided that subjects are on stable treatment
             for at least 3 months and have not had a seizure within the past 6 months.

          -  Independent in ambulation or ambulatory aided (example, walker or cane, wheelchair),
             vision and hearing (eyeglasses and/or hearing aid permissible) sufficient for
             achieving VABS-II/PCRF composite standard scores >55 and for cooperating with
             examinations and the Test of Verbal Expression and Reasoning (TOVER).

        Exclusion Criteria:

          -  Ages <10 or >17 years

          -  Active or clinically significant conditions affecting absorption, distribution or
             metabolism of the study medication (example, inflammatory bowel disease, gastric or
             duodenal ulcers or severe lactose intolerance)

          -  Known hypersensitivity to piperidine derivatives or cholinesterase inhibitors

          -  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

          -  No reliable parent or caregiver, or participants, or caregivers who are unwilling or
             unable to complete any of the outcome measures and fulfill the requirements of this
             study

          -  Clinically significant obstructive pulmonary disease or asthma untreated or not
             controlled by treatment within 3 months prior to screening

          -  Recent (less than or equal to 2 years) hematologic/oncologic disorders (mild anemia
             allowed)

          -  Evidence of active, clinically significant, and unstable gastrointestinal, renal,
             hepatic, endocrine or cardiovascular system disease

          -  Current Diagnostic and Statistical Manual IV Text Revision (DSM-IV-TR) diagnosis of
             Major Depressive Disorder (MDD) or any current primary psychiatric diagnosis other
             than DS (as per DSM-IV)

          -  Any condition which would make the subject or the caregiver, in the opinion of the
             investigator, unsuitable for the study

          -  Unsuitability which includes female subjects who have begun menstruation and are thus
             of child-bearing potential, who may be sexually active and who are not practicing an
             effective means of birth control.