Clinical trial NCT00570128: Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Down Syndrome
Keywords: Down Syndrome
trisomy 21
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
Collaborators: name: Pfizer
First posted: 2007-12-10
Enrollment: 129
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Primary outcomes:
measure: Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-Domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 10-Last Observation Carried Forward (LOCF)
timeFrame: Baseline, Week 10
Secondary outcomes:
measure: Mean Change From Baseline in V-Scale Composite Score (Sum of 9 Sub-domains) of Vineland Adaptive Behavior Scales Second Edition-Parent Caregiver Rating Form (VABS-II/PCRF) at Week 4 and 10-Observed Cases (OC)
timeFrame: Baseline, Week 4 and Week 10
measure: Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC
timeFrame: Baseline, Week 4 and Week 10
measure: Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF
timeFrame: Baseline, Week 10
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Phoenix Children's Hospital
state: Arizona
city: Little Rock
country: United States
facility: Clinical Study Centers, L.L.C.
state: Arkansas
city: Los Angeles
country: United States
facility: Neufeld Medical Group, Inc.
state: California
city: Oakland
country: United States
facility: Children's Hospital and Research Center at Oakland
state: California
city: Orange
country: United States
facility: University of California, Irvine Medical Center, Department of Pediatrics
state: California
city: San Diego
country: United States
facility: UCSD Pediatric Pharmacology Research Unit
state: California
city: Lakewood
country: United States
facility: Rocky Mountain Pediatrics
state: Colorado
city: Fort Myers
country: United States
facility: Neuropsychiatric Research Center of South West Florida
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital, Clinical Research Center
state: Florida
city: Miami
country: United States
facility: Community Research Foundation
state: Florida
city: Miami
country: United States
facility: Miami Children's Hospital, Brain Institute
state: Florida
city: Saint Petersburg
country: United States
facility: Meridien Research
state: Florida
city: West Palm Beach
country: United States
facility: Lazlo J. Mate, MD
state: Florida
city: Atlanta
country: United States
facility: Child Neurology Associates, PC
state: Georgia
city: Zionsville
country: United States
facility: Medical Genetics and Neuro Development Center
state: Indiana
city: Flint
country: United States
facility: Hurley Medical Center
state: Michigan
city: Grand Rapids
country: United States
facility: Saint Mayr's Health Care
state: Michigan
city: Saint Paul
country: United States
facility: Regions Hospital
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine, Division of Genetics and Genomic Medicine
state: Missouri
city: Lincoln
country: United States
facility: Midwest Children's Health Research Institute, LLC
state: Nebraska
city: Voorhees
country: United States
facility: Clinical Research Center of New Jersey
state: New Jersey
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Metrohealth Medical Center, Division of Psychiatry
state: Ohio
city: Toledo
country: United States
facility: Valko and Associates
state: Ohio
city: Tulsa
country: United States
facility: Tulsa Clinical Research LLC
state: Oklahoma
city: Charleston
country: United States
facility: Medical University of South Carolina, Division of Genetics and Developmental and Behavioral Pediatrics
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt Children's Hospital
state: Tennessee
city: Houston
country: United States
facility: Down Syndrome Clinic of Houston
state: Texas
city: San Antonio
country: United States
facility: Alamo City Clinical Research, LLC
state: Texas
city: San Antonio
country: United States
facility: Road Runner Research
state: Texas
city: Bellevue
country: United States
facility: Northwest Clinical Research Center
state: Washington
Study officials:
References: