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

NCT ID: NCT00754013

Last Updated: 2020-01-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2008-12-31

Brief 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.

Detailed Description

This is a multinational study with sites in the US, India, Singapore, South Korea, Mexico and Chile. There will be 210 subjects (male or female) enrolled that are residing in community or facilities with a reliable caregiver that have been clinically diagnosed with Down syndrome. The assessments performed during this study will be used to evaluate skills. The study duration will be 10 weeks of double blind treatment with a total of 6 visits; 4 in office visit and 2 phone visits.

Conditions

Down Syndrome; Cognitive Dysfunction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Donepezil

Group Type: ACTIVE_COMPARATOR

Aricept (Donepezil hydrochloride)

Intervention Type: DRUG

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.

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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.

Interventions

Aricept (Donepezil hydrochloride)

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.

Intervention Type: DRUG

Placebo

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 Type: DRUG

Other Intervention Names

Donepezil hydrochloride

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.

• 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.

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.

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 10 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Eisai Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas McRae, MD

Role: STUDY_DIRECTOR

Pfizer

Locations

Road Runner Research

San Antonio, Texas, United States

NeuroScience, Inc.

Herndon, Virginia, United States

Countries

United States

Other Identifiers

A2501061

Identifier Type: -

Identifier Source: secondary_id

E2020-A001-336

Identifier Type: -

Identifier Source: org_study_id