Evaluating 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

This study has been terminated.
(Sufficient evidence of efficacy not met. Discontinuation not based on any safety concerns.)
Sponsor:
Collaborator:
Pfizer
Information provided by:
Eisai Inc.
ClinicalTrials.gov Identifier:
NCT00754052
First received: September 15, 2008
Last updated: December 10, 2008
Last verified: December 2008
  Purpose

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.


Condition Intervention Phase
Down Syndrome, Cognitive Dysfunction
Drug: Aricept (donepezil hydrochloride)
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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, Aged 11 To 17

Resource links provided by NLM:


Further study details as provided by Eisai Inc.:

Primary Outcome Measures:
  • Vineland-II Adaptive Behavior Scale (VABS-II) Parent/Caregiver Rating Form (PCRF). [ Time Frame: Screen, Baseline, Week 4 and Week 10 or Early Termination. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Additional analyses of the VABS-II/PCRF including the composite score and domain and subdomain raw and standardized scores and Test of Verbal Expression and Reasoning (TOVER). [ Time Frame: Baseline, Week 4, and Week 10 or Early Termination; Leiter International Performance Scale-Revised (Leiter-R) subtests @ Screen, Baseline, Week 4, and Week 10 or Early Termination. ] [ Designated as safety issue: No ]

Estimated Enrollment: 192
Study Start Date: September 2008
Estimated Study Completion Date: April 2009
Estimated Primary Completion Date: April 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1 Drug: Aricept (donepezil hydrochloride)
All subjects will start with a dose of 2.5 mg/day (2.5 ml) donepezil ; dose escalation will occur at 2 weeks to a maximum of 5 mg/day (5 ml) donepezil. All doses will be administered orally.
Other Name: Donepezil hydrochloride
Active Comparator: 2 Drug: Aricept (donepezil hydrochloride)
All subjects will start with a dose of 2.5 mg/day (2.5 ml) donepezil ; dose escalations will occur every 2 weeks to a maximum of 10 mg/day (10 ml) donepezil. All doses will be administered orally.
Other Name: Donepezil hydrochloride
Placebo Comparator: 3 Drug: Placebo
All subjects will start with a dose of 2.5 mg/day (2.5 ml) placebo; dose escalations will occur every 2 weeks to a maximum of 10 mg/day (10 ml) placebo. All doses will be administered orally.

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 subjects to be enrolled.

  Eligibility

Ages Eligible for Study:   11 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age range: Subjects 11 to 17 years of age at the screening visit; weight >35 kg.
  2. Sex distribution: both males and females.
  3. VABS-II/PCRF receptive sub-domain raw score of >= 25 and expressive sub-domain raw score of >= 61.
  4. Clinical diagnosis of Down syndrome (DS) - subjects may have free trisomy 21, Robertsonian translocations, or mosaic DS.
  5. 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.
  6. Subjects residing in the community or in facilities that have consistent and reliable caregivers who can provide efficacy information about the subjects.
  7. 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.
  8. 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.
  9. 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.
  10. Subjects should be in good general health with no medical conditions that are considered both clinically significant and unstable.
  11. Clinical laboratory values within normal limits or abnormalities considered not clinically significant by the investigator and sponsor.
  12. 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).
  13. 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.
  14. 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.
  15. 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.
  16. Females who have begun menstruation and are thus of child-bearing potential may be enrolled but must be documented not to be pregnant by serum pregnancy testing at screening. They also must be practicing an effective means of birth control (abstinence, oral contraceptives, hormonal implants in place at least 1 month prior to enrollment, or a double-barrier method), which must be documented, and the subject and caregiver must be counseled in writing of the importance of not becoming pregnant during the trial. A urine pregnancy test will be done at the Week 4 clinic visit and must be negative prior to dispensing any medication; a serum pregnancy test will be repeated at the Week 10 (or Early Termination) clinic visit.

Exclusion Criteria:

  1. Age range: Subjects <11 or >17 years at the screening visit.
  2. 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.
  3. Subjects with a known hypersensitivity to piperidine derivatives or cholinesterase inhibitors.
  4. 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.
  5. 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.
  6. Subjects with clinically significant obstructive pulmonary disease or asthma, untreated or not controlled by treatment within 3 months prior to screening.
  7. Subjects with recent (<= 1 year) or ongoing hematologic/oncologic disorders (mild anemia allowed).
  8. Evidence of active, clinically significant, and unstable gastrointestinal, renal, hepatic, endocrine or cardiovascular system disease.
  9. 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.
  10. Any condition which would make the patient or the caregiver, in the opinion of the investigator, unsuitable for the study. Unsuitability includes female subjects who have begun menstruation and are thus of child-bearing potential, and who are not practicing an effective means of birth control. Female subjects 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00754052

Locations
United States, Texas
Road Runner Research
San Antonio, Texas, United States, 78258
United States, Virginia
Neuroscience, Inc
Herndon, Virginia, United States, 20170
Sponsors and Collaborators
Eisai Inc.
Pfizer
Investigators
Study Director: Thomas McRae, MD Pfizer
  More Information

No publications provided

Responsible Party: Eisai Medical Affairs, Eisai Inc.
ClinicalTrials.gov Identifier: NCT00754052     History of Changes
Other Study ID Numbers: E2020-A001-335, A2501061
Study First Received: September 15, 2008
Last Updated: December 10, 2008
Health Authority: United States: Institutional Review Board
European Union: European Medicines Agency

Keywords provided by Eisai Inc.:
Pediatric
Down syndrome
Downs
Cognitive Dysfunction of Down syndrome

Additional relevant MeSH terms:
Down Syndrome
Cognition Disorders
Mental Retardation
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Abnormalities, Multiple
Congenital Abnormalities
Chromosome Disorders
Genetic Diseases, Inborn
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Donepezil
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 20, 2014