- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00754013
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
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 6 To 10
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
-
-
Texas
-
San Antonio, Texas, United States, 78258
- Road Runner Research
-
-
Virginia
-
Herndon, Virginia, United States, 20170
- Neuroscience, Inc.
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
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.
- Subjects 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: 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. |
Active Comparator: Donepezil
|
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.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Vineland-II Adaptive Behavior Scales (VABS-II) Parent/Caregiver Rating Form (PCRF) 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.
Time Frame: Visit 0 (Screen), Visits 1 (Baseline), 2, and 3 (or Early Termination).
|
The primary objective of the study was evaluation of the efficacy and safety of donepezil hydrochloride in the treatment of the cognitive dysfunction exhibited by children with Down syndrome (DS), aged 6 to 10, as assessed by analysis of VABS-II/PCRF in the domains of communication, daily living skills, and socialization, and as assessed by standard safety measurements.
|
Visit 0 (Screen), Visits 1 (Baseline), 2, and 3 (or Early Termination).
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Change From(Baseline) to Visit 3(Week 10 or Early Termination) in VABS-II/PCRF 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.
Time Frame: Visit 1 (Baseline) to Visit 3 (Week 10 or early termination).
|
The planned secondary objectives of the study included further evaluation of efficacy as assessed by additional analyses of the VABS-II/PCRF, by analyses of the Test of Verbal Expression and Reasoning (TOVER), a subject-performance-based measure of expressive language function, and by the Forward Memory and Attention Sustained sub-tests of the Leiter International Performance Scale - Revised (Leiter-R), a cognitive assessment instrument for children and adolescents that is not language dependent.
In addition, observed case analyses of these assessments at Week 4 and Week 10 were planned.
|
Visit 1 (Baseline) to Visit 3 (Week 10 or early termination).
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
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-A001-336
- A2501061
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Cognitive Dysfunction
-
Loma Linda UniversityCompleted1. Postoperative Cognitive DysfunctionUnited States
-
Shanghai Ninth People's Hospital Affiliated to...RecruitingPOCD - Postoperative Cognitive DysfunctionChina
-
Mu Dong LiangNot yet recruitingPostoperative Cognitive Dysfunction(POCD)
-
HealthPartners InstituteEnrolling by invitationPost Operative Cognitive DysfunctionUnited States
-
Burcu Ozalp HorsanaliCompletedPost Operative Cognitive Dysfunction
-
ImmunoChem Therapeutics, LLCNational Cancer Institute (NCI); Northwestern MedicineRecruitingCognitive Dysfunction, Cognitive DisorderUnited States
-
Attikon HospitalCompleted
-
Mayo ClinicCompletedCognitive Impairment | Mild Cognitive Impairment | Neurocognitive DysfunctionUnited States
-
Xijing HospitalFirst Affiliated Hospital Xi'an Jiaotong University; Shanghai 10th People's... and other collaboratorsTerminatedPost Operative Cognitive DysfunctionChina
-
Icahn School of Medicine at Mount SinaiNational Institute on Aging (NIA)CompletedPost Operative Cognitive DysfunctionUnited States
Clinical Trials on Aricept (Donepezil hydrochloride)
-
Eisai Inc.Eisai LimitedCompleted
-
Eisai Inc.PfizerWithdrawnSevere Alzheimer's DiseaseUnited States
-
Eisai Co., Ltd.CompletedDementia With Lewy Bodies (DLB)Japan
-
Eisai Inc.PfizerTerminatedCognitive Dysfunction | Down SyndromeUnited States
-
Eisai Inc.CompletedMigraine HeadacheUnited States
-
Eisai Inc.Eisai Co., Ltd.CompletedVascular DementiaPhilippines
-
Dr. Reddy's Laboratories LimitedCompleted
-
Eisai Inc.CompletedMild Cognitive ImpairmentUnited States
-
Dr. Reddy's Laboratories LimitedCompleted
-
Teva Pharmaceuticals USACompletedHealthyUnited States