Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome

NCT00570128 | Completed Phase 2 Results DMC

• 2 other identifiers: E2020-A001-219A2501059
• Study Type: interventional
• Target: 129
• Locations: 1 country
• Sites: 31

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.

Conditions

Down Syndrome

Keywords

Down Syndrome; trisomy 21

Outcome Measures

Primary Outcomes (1)

• 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)

  The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, and writing), daily living skills (sub-domains: personal, domestic, community), and socialization (sub-domains: interpersonal relationships, play/leisure time, coping skills). Raw scores (2=always present, 1=sometimes present, 0=seldom or never present) rated by the parent/caregiver from each sub-domain were converted to standardized scores called V-scores, which are based on age and a national sample of normal children. Each sub-domain v-scale score ranged from 1 (weakness) to 24 (strength). V-scores for the 9 sub-domains were summed to obtain a composite V-score ranging from 9 to 216. Higher scores indicate a higher level of adaptive functioning. A positive change from baseline indicates an improvement in adaptive functioning. Composite V-scores have a mean (50th percentile) of 100 and a standard deviation (SD) of 15.

  Baseline, Week 10

Secondary Outcomes (3)

• 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)

  Baseline, Week 4 and Week 10

• Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 4 and 10-OC

  Baseline, Week 4 and Week 10

• Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF

  Baseline, Week 10

Study Arms (2)

Donepezil HCl

ACTIVE COMPARATOR

Drug: Donepezil HCl

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Donepezil HCl DRUG

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).

Also known as: Aricept

Donepezil HCl

Placebo DRUG

Liquid formulation matched to active treatment for oral administration.

Placebo

Eligibility Criteria

• Age: 10 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eisai Inc.: lead
• Pfizer: collaborator

Study Sites (31)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Clinical Study Centers, L.L.C.

Little Rock, Arkansas, 72205, United States

Location

Neufeld Medical Group, Inc.

Los Angeles, California, 90048, United States

Location

Children's Hospital and Research Center at Oakland

Oakland, California, 94609, United States

Location

University of California, Irvine Medical Center, Department of Pediatrics

Orange, California, 92868, United States

Location

UCSD Pediatric Pharmacology Research Unit

San Diego, California, 92123, United States

Location

Rocky Mountain Pediatrics

Lakewood, Colorado, 80214, United States

Location

Neuropsychiatric Research Center of South West Florida

Fort Myers, Florida, 33912, United States

Location

Miami Children's Hospital, Clinical Research Center

Miami, Florida, 33155-3009, United States

Location

Community Research Foundation

Miami, Florida, 33155, United States

Location

Miami Children's Hospital, Brain Institute

Miami, Florida, 33155, United States

Location

Meridien Research

St. Petersburg, Florida, 33709, United States

Location

Lazlo J. Mate, MD

West Palm Beach, Florida, 33407, United States

Location

Child Neurology Associates, PC

Atlanta, Georgia, 30342, United States

Location

Medical Genetics and Neuro Development Center

Zionsville, Indiana, 46077, United States

Location

Hurley Medical Center

Flint, Michigan, 48503, United States

Location

Saint Mayr's Health Care

Grand Rapids, Michigan, 49503, United States

Location

Regions Hospital

Saint Paul, Minnesota, 55101-2529, United States

Location

Washington University School of Medicine, Division of Genetics and Genomic Medicine

St Louis, Missouri, 63110, United States

Location

Midwest Children's Health Research Institute, LLC

Lincoln, Nebraska, 68504, United States

Location

Clinical Research Center of New Jersey

Voorhees Township, New Jersey, 08043, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Metrohealth Medical Center, Division of Psychiatry

Cleveland, Ohio, 44109, United States

Location

Valko and Associates

Toledo, Ohio, 43606, United States

Location

Tulsa Clinical Research LLC

Tulsa, Oklahoma, 74104-5428, United States

Location

Medical University of South Carolina, Division of Genetics and Developmental and Behavioral Pediatrics

Charleston, South Carolina, 29425, United States

Location

Vanderbilt Children's Hospital

Nashville, Tennessee, 37232-9225, United States

Location

Down Syndrome Clinic of Houston

Houston, Texas, 77030, United States

Location

Alamo City Clinical Research, LLC

San Antonio, Texas, 78258, United States

Location

Road Runner Research

San Antonio, Texas, 78258, United States

Location

Northwest Clinical Research Center

Bellevue, Washington, 98004, United States

Location

MeSH Terms

Conditions

Down Syndrome

Interventions

Donepezil

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Eisai Medical Information
• Organization: Eisai Inc.

esi_medinfo@eisai.com

+1-888-274-2378

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2007
• First Posted: December 10, 2007
• Study Start: November 16, 2007
• Primary Completion: September 5, 2008
• Study Completion: September 5, 2008
• Last Updated: April 19, 2021
• Results First Posted: April 19, 2021

Record last verified: 2021-03

Locations

US (31)