Down SyndromePhase 2NCT00570128
Evaluating The Efficacy And Safety Of Donepezil Hydrochloride (HCl) (Aricept) In Treating Cognitive Dysfunction Exhibited By Children With Down Syndrome
A Phase 2 study testing Donepezil HCl in people with Down Syndrome, run by Eisai Inc. at 31 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 10 to 17 years
- Conditions the study is for
- Down Syndrome
- What is being tested?
- Donepezil HCl
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 129 participants
- Where
- 31 sitesUnited States
- Study dates
- 16 Nov 2007to 5 Sep 2008
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 10 to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- 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
Show all 16Show fewer
- 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).
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
31 sites in 1 country.
31 sites in 1 country
United States31 sites
Child Neurology Associates, PC
Atlanta, Georgia, 30342
Northwest Clinical Research Center
Bellevue, Washington, 98004
Medical University of South Carolina, Division of Genetics and Developmental and Behavioral Pediatrics
Charleston, South Carolina, 29425
Metrohealth Medical Center, Division of Psychiatry
Cleveland, Ohio, 44109
Duke University Medical Center
Durham, North Carolina, 27710
Hurley Medical Center
Flint, Michigan, 48503
Neuropsychiatric Research Center of South West Florida
Fort Myers, Florida, 33912
Saint Mayr's Health Care
Grand Rapids, Michigan, 49503
Down Syndrome Clinic of Houston
Houston, Texas, 77030
Rocky Mountain Pediatrics
Lakewood, Colorado, 80214
Midwest Children's Health Research Institute, LLC
Lincoln, Nebraska, 68504
Clinical Study Centers, L.L.C.
Little Rock, Arkansas, 72205
Neufeld Medical Group, Inc.
Los Angeles, California, 90048
Miami Children's Hospital, Clinical Research Center
Miami, Florida, 33155-3009
Community Research Foundation
Miami, Florida, 33155
Miami Children's Hospital, Brain Institute
Miami, Florida, 33155
Vanderbilt Children's Hospital
Nashville, Tennessee, 37232-9225
Children's Hospital and Research Center at Oakland
Oakland, California, 94609
University of California, Irvine Medical Center, Department of Pediatrics
Orange, California, 92868
Phoenix Children's Hospital
Phoenix, Arizona, 85016
Regions Hospital
Saint Paul, Minnesota, 55101-2529
Alamo City Clinical Research, LLC
San Antonio, Texas, 78258
Road Runner Research
San Antonio, Texas, 78258
UCSD Pediatric Pharmacology Research Unit
San Diego, California, 92123
Washington University School of Medicine, Division of Genetics and Genomic Medicine
St Louis, Missouri, 63110
Meridien Research
St. Petersburg, Florida, 33709
Valko and Associates
Toledo, Ohio, 43606
Tulsa Clinical Research LLC
Tulsa, Oklahoma, 74104-5428
Clinical Research Center of New Jersey
Voorhees Township, New Jersey, 08043
Lazlo J. Mate, MD
West Palm Beach, Florida, 33407
Medical Genetics and Neuro Development Center
Zionsville, Indiana, 46077
About this study
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
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
- Being tested
- Donepezil HCl, Placebo
- Keywords
- Down Syndrome, trisomy 21
- Medical subject headings
- Down Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Donepezil HClDrug
Also called Aricept
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).
PlaceboDrug
Liquid formulation matched to active treatment for oral administration.
| Study group | Role | What they receive |
|---|---|---|
| Donepezil HCl | Active comparator | Not described Receives: Drug: Donepezil HCl |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
The VABS-II/PCRF instrument was used in this study to assess 3 domains (each with 3 sub-domains): communication (sub-domains: receptive, expressive, 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 SD of 15.
Measured: 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
The TOVER is a participant-performance-based measure of expressive language function and verbal reasoning in response to questions about a series of stylized pictures showing identifiable scenarios. The 64-item test was specifically designed to assess language function in children and adults with down syndrome (DS) across a broad range of functional ability. The test used 23 multi-colored pictures to stimulate verbal responses to questions. The test was short (completed in 15 minutes) and fast-paced (2 to 4 questions per picture). Total score ranging from 0 to 64, was derived from 64 questions, where higher score indicates better functional ability.
Measured: Baseline, Week 4 and Week 10
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF
The TOVER is a participant-performance-based measure of expressive language function and verbal reasoning in response to questions about a series of stylized pictures showing identifiable scenarios. The 64-item test was specifically designed to assess language function in children and adults with DS across a broad range of functional ability. The test used 23 multi-colored pictures to stimulate verbal responses to questions. The test was short (completed in 15 minutes) and fast-paced (2 to 4 questions per picture). Total score ranging from 0 to 64, was derived from 64 questions, where higher score indicates better functional ability.
Measured: Baseline, Week 10
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2007 (estimated)
- Study start16 Nov 2007
- Primary completion5 Sep 2008
- Study completion5 Sep 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Down SyndromeStudies of the same condition, open and under way.
- More trials run by Eisai Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 129 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00570128
- Sponsor's protocol ID
- E2020-A001-219
- Other IDs
- A2501059
- Status last verified
- Mar 2021
- First submitted
- 6 Dec 2007
- Last updated
- 19 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00570128
- Acronym / sponsor ID
- E2020-A001-219
- Conditions
- Down Syndrome
- Keywords
- Down Syndrome, trisomy 21
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 129 participants (actual)
- Lead sponsor
- Eisai Inc.Industry (pharma, biotech, devices)
- Collaborators
- Pfizer
- Study start
- 16 Nov 2007 (actual)
- Primary completion
- 5 Sep 2008 (actual)
- Study completion
- 5 Sep 2008 (actual)
- First posted
- 10 Dec 2007 (estimated)
- Results
- Posted 19 Apr 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Donepezil HCl | Active comparator | Drug: Donepezil HCl |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 10 to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (16 listed)
- 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.
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Donepezil HClAlso: AriceptBlinded 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). | Drug | Donepezil HCl |
| PlaceboLiquid formulation matched to active treatment for oral administration. | Drug | Placebo |
Primary outcome
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)
Time frame: Baseline, Week 10
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.
3 secondary outcomes
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)
Time frame: 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
Time frame: Baseline, Week 4 and Week 10
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER) Total Score at Week 10-LOCF
Time frame: Baseline, Week 10
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Down Syndrome
Not yet recruitingPhase 4
Oral Switch in Bloodstream Infections in Immunocompromised Children
Bloodstream Infection, Bloodstream Infection Due to Central Venous Catheter
Not yet recruiting
Fecal Microbiota Transplantation (FMT) to Slow Biological Aging
Aging, Healthy, Aging and Cognitive Health
Active, not recruitingPhase 3
A Study to Investigate Blinatumomab in Combination With Chemotherapy in Patients With Newly Diagnosed B-Lymphoblastic Leukemia
B Acute Lymphoblastic Leukemia, B Lymphoblastic Lymphoma
Not yet recruiting
Executive Function Play Opportunities for Children With Down Syndrome
Down Syndrome, Trisomy 21
RecruitingObservational study
Natural History of Dysregulation and Aging of the Immune System in People With Trisomy 21 With and Without Thymectomy
Down Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
31 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Donepezil HCl in people with Down Syndrome, run by Eisai Inc. at 31 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 31 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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) (time frame: Baseline, Week 10). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Apr 2021.