Evaluating The Safety Of Donepezil Hydrochloride (Aricept) For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome - Follow-Up To A 10-Week, Double-Blind, Placebo-Controlled Trial

An Open-label Study to Evaluate the Safety of Donepezil Hydrochloride((Aricept®) for up to 1 Year in the Treatment of Cognitive Dysfunction Exhibited by Children With Down Syndrome-Follow-up to a 10-Week,Double-Blind,Placebo-Controlled Trial

The purpose of this study is to determine the safety of donepezil hydrochloride (Aricept) in children with Down syndrome who have finished the preceding 10-week, double-blind study of donepezil hydrochloride. Medical tests for drug safety will be conducted at each clinic visit.

Study Overview

• Status: Terminated
• Conditions: Down Syndrome
• Intervention / Treatment: Drug: Donepezil hydrochloride (Aricept)

Detailed Description

All children in this study will take donepezil hydrochloride once a day, and will come back to the clinic at 8, 24 and 42 weeks after the study has begun. In between these clinic visits, the clinical staff will telephone the child's parent or caregiver to discuss drug safety observations and possible changes in drug dose. At the end of the study (42 weeks), psychological testing will also be given to determine how well the child is functioning.

• Study Type: Interventional
• Enrollment (Actual): 117
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Hospital
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Child Neurology Associates, PC
  • California
    • Los Angeles, California, United States, 90048
      • Midwest Children's Health Research Institute
    • Oakland, California, United States, 94609
      • Children's Hospital and Research Center at Oakland
    • Orange, California, United States, 92868
      • University of California, Irvine Medical Center
    • San Diego, California, United States, 92123
      • UCSD Pediatric Pharmacology Research Unit
  • Colorado
    • Lakewood, Colorado, United States, 80214
      • Rocky Mountain Pediatrics, P.C.
  • Florida
    • Fort Myers, Florida, United States, 33912
      • Neufeld Medical Group, Inc.
    • Miami, Florida, United States, 33155-3009
      • Miami Children's Hospital
    • Miami, Florida, United States, 33155
      • Miami Children's Hospital - Medical Genetics and Neuro-Developmental Center
    • Miami, Florida, United States, 33155
      • Phoenix Children's Hospital
    • Saint Petersburg, Florida, United States, 33709
      • Clinical Studies Centers, LLC
    • West Palm Beach, Florida, United States, 33407
      • Northwest Clinical Research Center
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Road Runner Research
  • Michigan
    • Flint, Michigan, United States, 48503
      • Hurley Medical Center
    • Grand Rapids, Michigan, United States, 49503
      • Saint Mary's Health Care
    • Grand Rapids, Michigan, United States, 49503
      • Washington University School of Medicine
  • Minnesota
    • Saint Paul, Minnesota, United States, 55101-2595
      • Regions Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Northwest Clinical Research Center
  • Nebraska
    • Lincoln, Nebraska, United States, 68504
      • Meridien Research
  • New Jersey
    • Voorhees, New Jersey, United States, 08043
      • Clinical Research Center Of New Jersey
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Division of Genetics and Developmental Behavior
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
    • Toledo, Ohio, United States, 43606
      • Valko and Associates
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Office of Lazlo Mate
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical Univ of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37232-9225
      • Vanderbilt Children's Hospital
  • Texas
    • Houston, Texas, United States, 77030
      • Down Syndrome Clinic of Houston
    • San Antonio, Texas, United States, 78258
      • Alamo City Clinical Research, LLC
    • San Antonio, Texas, United States, 78258
      • Community Research Foundation
  • Washington
    • Bellevue, Washington, United States, 98004
      • Neuropsychiatric Research Center of Southwest Florida

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Diagnosis of Down syndrome (established during study E2020-A001-220).
• Completion of study E2020-A001-219 (NCT00570128 [also known as A2501059]) with no ongoing seroius adverse events and no severe drug reactions.

Exclusion Criteria:

• Weight less than 20 kg.
• Clinically significant conditions affecting absorption, distribution or metabolism of the study medication.
• No reliable parent or caregiver, or unwillingness or inability of parent or caregiver to fulfill the requirements of the study.
• Females of childbearing potential who are not practicing an effective means of birth control.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Prior Donepezil-DB; All participants started with a dose of 2.5 mg/day (2.5 mL/day). Dose escalations occurred in 2.5 mg/day increments every 2 weeks (steady state levels assumed to have been reached) to a maximum dose of 10 mg/day, according to the participant's weight schedule and the Investigator's judgment of safety and tolerability. Re-titration was done to maintain the blinding of the double-blind study (E2020-A001-219). Doses could be decreased due to tolerability and could be increased or decreased to maintain a maximum dose of 0.1 to 0.2 mg/kg/day based on the participant's weight at clinic visits during the study duration.

Drug: Donepezil hydrochloride (Aricept); Liquid form Aricept - 5 mg/5 mL donepezil hydrochloride.; Other Names: Aricept

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Visit 1 (Baseline) to Visit 4 or Early Termination in the Vineland Adaptive Behavior Scales, 2nd Edition, Parent/Caregiver Rating Form (VABS-II/PCRF) Sum of the 9 Sub-domain V-scores	VABS-II/PCRF assessed participant's adaptive behaviors on 3 domains (each has 3 sub-domains): Communication (receptive, expressive, written), Daily Living Skills (personal, domestic, community), Socialization (interpersonal relationships, play a leisure time, coping skills). Parent/caregiver rated participant's behavior for sub-domains from 0 (never present) to 2 (always present). Raw scores from sub-domains converted into standardized score(V-scale scores) ranged:1-24 for each sub-domain, mean=15,standard deviation(SD)=3,higher scores=higher level of adaptive functioning and were summed to obtain V-scale composite score ranged 9-216, mean=100,SD=15,higher scores=higher level of adaptive functioning, positive change=improvement in adaptive functioning. Composite and individual analyses, both raw and standardized scores, were not performed due to lack of significant differences between donepezil and placebo in parent study.	Visit 1 (baseline); Early Termination Visit (Week 36)

Collaborators and Investigators

• Sponsor: Eisai Inc.
• Collaborators: Pfizer

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2008
• Primary Completion (Actual): November 13, 2008
• Study Completion (Actual): December 15, 2008

Study Registration Dates

• First Submitted: May 7, 2008
• First Submitted That Met QC Criteria: May 7, 2008
• First Posted (Estimate): May 8, 2008

Study Record Updates

• Last Update Posted (Actual): March 29, 2021
• Last Update Submitted That Met QC Criteria: March 26, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Intellectual Disability; Cognition Disorders; Abnormalities, Multiple; Chromosome Disorders; Syndrome; Cognitive Dysfunction; Down Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Nootropic Agents; Cholinesterase Inhibitors; Donepezil
• Other Study ID Numbers: E2020-A001-220; A2501060 (Other Identifier: Pfizer)