A 10-Week, Double-Blind, Placebo-Controlled Study To Evaluate 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

Eisai Inc.2 sites in 1 country8 target enrollmentSeptember 2008

ConditionsDown Syndrome Cognitive Dysfunction

InterventionsAricept (donepezil hydrochloride)Placebo

DrugsAricept (donepezil hydrochloride)Placebo

Overview

Phase: Phase 3
Intervention: Aricept (donepezil hydrochloride)
Conditions: Down Syndrome
Sponsor: Eisai Inc.
Enrollment: 8
Locations: 2
Primary Endpoint: Mean Change From Baseline in Vineland-II Adaptive Behavior Scale (VABS-II) Parent/Caregiver Rating Form (PCRF) Score Using Last Observation Carried Forward (LOCF)
Status: Terminated
Last Updated: 8 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this study is to determine the efficacy and safety of donepezil hydrochloride (Aricept) in the treatment of the cognitive dysfunction shown by children with Down syndrome, aged 11 to 17.

Detailed Description

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.

Registry

clinicaltrials.gov

Start Date

September 2008

End Date

December 2008

Last Updated

8 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Eisai Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Age range: Participants 11 to 17 years of age at the screening visit; weight \>35 kilograms (kg).
•Sex distribution: both males and females.
•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 \>=
•Clinical diagnosis of Down syndrome (DS) - participants 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 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.
•Participants residing in the community or in facilities that have consistent and reliable caregivers who can provide efficacy information about the participants.
•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.
•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.
•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.
•Participants should be in good general health with no medical conditions that are considered both clinically significant and unstable.

Exclusion Criteria

•Age range: Participants \<11 or \>17 years at the screening visit.
•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.
•Participants with a known hypersensitivity to piperidine derivatives or cholinesterase inhibitors.
•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.
•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.
•Participants with clinically significant obstructive pulmonary disease or asthma, untreated or not controlled by treatment within 3 months prior to screening.
•Participants 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.
•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.
•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.

Arms & Interventions

1

Intervention: Aricept (donepezil hydrochloride)

2

Intervention: Aricept (donepezil hydrochloride)

3

Intervention: Placebo

Outcomes

Primary Outcomes

Mean Change From Baseline in Vineland-II Adaptive Behavior Scale (VABS-II) Parent/Caregiver Rating Form (PCRF) Score Using Last Observation Carried Forward (LOCF)

Time Frame: Baseline (Day 0) to Visit 3 (Week 10) or at early termination

Mean change from Baseline from Visit 1 (baseline) to Visit 3 (Week 10 or early termination) in VABS-11/PCRF, a sum of the 9 sub-domain v-scores (3 scores for each of the communication, daily living skills, and socialization domains) using last observation carried forward was planned.

Secondary Outcomes

Mean Change From Baseline in Additional Analyses of the VABS-11/PCRF(Baseline (Day 0) to Visit 3 (Week 10) or early termination)
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER)(Baseline (Day 0) to Visit 3 (Week 10) or early termination)
Mean Change From Baseline if the Forward Memory and Attention Sustained Sub-tests of the Leiter International Performance Scale - Revised (Leiter-R)(Baseline (Day 0) to Visit 3 (Week 10) or early termination)