Down SyndromePhase 3NCT00754052

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

A Phase 3 study testing Aricept (donepezil hydrochloride) in people with Down Syndrome and Cognitive Dysfunction, run by Eisai Inc. at 2 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

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. Read more about this study

Who is it for?: Ages 11 to 17 years
Conditions the study is for: Down Syndrome, Cognitive Dysfunction
What is being tested?: Aricept (donepezil hydrochloride)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 8 participants
Where: 2 sitesUnited States
Study dates: Sep 2008to Dec 2008
Phase: Phase 3
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 11 to 17 years
All sexes
No healthy volunteers
Child

Who may be able to join

Age range: Participants 11 to 17 years of age at the screening visit; weight >35 kilograms (kg).
Sex distribution: both males and females.
Vineland-II Adaptive Behavior Scales (VABS-II)/Parent/Caregiver Rating Form (PCRF) receptive sub-domain raw score of >= 25 and expressive sub-domain raw score of >= 61.
Clinical diagnosis of Down syndrome (DS) - participants 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 participant in the study. The exception to this prior use is that participants who participated in the Phase II study E2020-A001-219 (A2501059) are not eligible.
Participants residing in the community or in facilities that have consistent and reliable caregivers who can provide efficacy information about the participants.

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The participants must be expected to complete all procedures scheduled during the Screening and Baseline visits including all efficacy and safety parameters. Participants 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.
Participants must have a parent, or other reliable caregiver who agrees to accompany the participant to all clinic visits, provide information about the participant 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 participant to have detailed knowledge of the participant'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.
Participants 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.
Participants 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).
Participants 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.
Participants 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.
Participants 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.
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 participant 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.

Who cannot join

Age range: Participants <11 or >17 years at the screening visit.
Participants 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.
Participants with a known hypersensitivity to piperidine derivatives or cholinesterase inhibitors.
Participants 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 participant in this study. Also excluded are participants who participated in the Phase II study E2020-A001-219 (A2501059). In addition, participants may not have taken any other investigational medications (including memantine) within 3 months prior to screening.
Participants 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.
Participants with clinically significant obstructive pulmonary disease or asthma, untreated or not controlled by treatment within 3 months prior to screening.

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Participants 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.
Participants 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. Unsuitability includes female participants who have begun menstruation and are thus of child-bearing potential, and who are not practicing an effective means of birth control. Female participants 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

Neuroscience, Inc
Herndon, Virginia, 20170
Road Runner Research
San Antonio, Texas, 78258

Other trials in United States

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, Aged 11 To 17

Read the 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 participants to be enrolled.

Conditions: Down Syndrome, Cognitive Dysfunction
Being tested: Aricept (donepezil hydrochloride), Placebo
Keywords: Pediatric, Down syndrome, Downs, Cognitive Dysfunction of Down syndrome
Medical subject headings: Down Syndrome, Cognitive Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Aricept (donepezil hydrochloride)Drug
Also called Donepezil hydrochloride
All participants will start with a dose of 2.5 mg/day (2.5 ml) donepezil ; dose escalation will occur every 2 weeks to a maximum of 5 mg/day (5 ml) donepezil. All doses will be administered orally.
Aricept (donepezil hydrochloride)Drug
Also called Donepezil hydrochloride
All participants 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.
PlaceboDrug
All participants 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.

Study groups in NCT00754052
Study group	Role	What they receive
1	Active comparator	Not described Receives: Drug: Aricept (donepezil hydrochloride)
2	Active comparator	Not described Receives: Drug: Aricept (donepezil hydrochloride)
3	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 Vineland-II Adaptive Behavior Scale (VABS-II) Parent/Caregiver Rating Form (PCRF) Score Using Last Observation Carried Forward (LOCF)
Mean change from Baseline from Visit 1 (baseline) to Visit 3 (Week 10 or early termination) in VABS-11/PCRF, a 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 was planned.
Measured: Baseline (Day 0) to Visit 3 (Week 10) or at early termination

Secondary outcomes (3)

Mean Change From Baseline in Additional Analyses of the VABS-11/PCRF
Additional analyses of the VABS-II/PCRF were planned.
Measured: Baseline (Day 0) to Visit 3 (Week 10) or early termination
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER)
TOVER, a subject performance-based measure of expressive language function was planned.
Measured: Baseline (Day 0) to Visit 3 (Week 10) or early termination
Mean Change From Baseline if the Forward Memory and Attention Sustained Sub-tests of the Leiter International Performance Scale - Revised (Leiter-R)
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 was planned.
Measured: Baseline (Day 0) to Visit 3 (Week 10) or early termination

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Sep 2008Dec 2008

First posted17 Sep 2008 (estimated)
Study startSep 2008
Primary completionNov 2008
Study completionDec 2008

Why it stopped: Sufficient evidence of efficacy not met. Discontinuation not based on any safety concerns.

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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 8 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00754052
Sponsor's protocol ID: E2020-A001-335
Other IDs: A2501061
Status last verified: Mar 2018
First submitted: 15 Sep 2008
Last updated: 23 Apr 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 Apr 2018. 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, Aged 11 To 17
ClinicalTrials.gov ID: NCT00754052
Acronym / sponsor ID: E2020-A001-335
Conditions: Down Syndrome, Cognitive Dysfunction
Keywords: Pediatric, Down syndrome, Downs, Cognitive Dysfunction of Down syndrome
Phase: Phase 3
Study type: Interventional
Recruitment status: TerminatedReason stopped: Sufficient evidence of efficacy not met. Discontinuation not based on any safety concerns.
Enrolment: 8 participants (actual)
Lead sponsor: Eisai Inc.Industry (pharma, biotech, devices)
Collaborators: Pfizer
Study start: Sep 2008
Primary completion: Nov 2008 (actual)
Study completion: Dec 2008 (actual)
First posted: 17 Sep 2008 (estimated)
Results: Posted 23 Apr 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 participants to be enrolled.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 3

Arm	Type	Receives
1	Active comparator	Drug: Aricept (donepezil hydrochloride)
2	Active comparator	Drug: Aricept (donepezil hydrochloride)
3	Placebo comparator	Drug: Placebo

Who may qualify

Ages: 11 to 17 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child

Key inclusion criteria (16 listed)

Age range: Participants 11 to 17 years of age at the screening visit; weight >35 kilograms (kg).
Sex distribution: both males and females.
Vineland-II Adaptive Behavior Scales (VABS-II)/Parent/Caregiver Rating Form (PCRF) receptive sub-domain raw score of >= 25 and expressive sub-domain raw score of >= 61.
Clinical diagnosis of Down syndrome (DS) - participants 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 participant in the study. The exception to this prior use is that participants who participated in the Phase II study E2020-A001-219 (A2501059) are not eligible.

Key exclusion criteria (10 listed)

Age range: Participants <11 or >17 years at the screening visit.
Participants 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.
Participants with a known hypersensitivity to piperidine derivatives or cholinesterase inhibitors.
Participants 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 participant in this study. Also excluded are participants who participated in the Phase II study E2020-A001-219 (A2501059). In addition, participants may not have taken any other investigational medications (including memantine) within 3 months prior to screening.
Participants 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.

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
Aricept (donepezil hydrochloride)Also: Donepezil hydrochlorideAll participants will start with a dose of 2.5 mg/day (2.5 ml) donepezil ; dose escalation will occur every 2 weeks to a maximum of 5 mg/day (5 ml) donepezil. All doses will be administered orally.	Drug	1
Aricept (donepezil hydrochloride)Also: Donepezil hydrochlorideAll participants 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.	Drug	2
PlaceboAll participants 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.	Drug	3

Primary outcome

Mean Change From Baseline in Vineland-II Adaptive Behavior Scale (VABS-II) Parent/Caregiver Rating Form (PCRF) Score Using Last Observation Carried Forward (LOCF)
Time frame: Baseline (Day 0) to Visit 3 (Week 10) or at early termination
Mean change from Baseline from Visit 1 (baseline) to Visit 3 (Week 10 or early termination) in VABS-11/PCRF, a 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 was planned.

3 secondary outcomes

Mean Change From Baseline in Additional Analyses of the VABS-11/PCRF
Time frame: Baseline (Day 0) to Visit 3 (Week 10) or early termination
Mean Change From Baseline in Test of Verbal Expression and Reasoning (TOVER)
Time frame: Baseline (Day 0) to Visit 3 (Week 10) or early termination
Mean Change From Baseline if the Forward Memory and Attention Sustained Sub-tests of the Leiter International Performance Scale - Revised (Leiter-R)
Time frame: Baseline (Day 0) to Visit 3 (Week 10) or early termination

Results and safety

Results posted to the registry on 23 Apr 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Donepezil Hydrochloride	5	0
Placebo	3	0

Primary outcome: Mean Change From Baseline in Vineland-II Adaptive Behavior Scale (VABS-II) Parent/Caregiver Rating Form (PCRF) Score Using Last Observation Carried Forward (LOCF)

Time frame: Baseline (Day 0) to Visit 3 (Week 10) or at early termination

Population analysed: Because the study was terminated early, only 8 subjects were enrolled. Analyses were not performed due to study medication exposure being limited and variable, limited efficacy data were collected, and no participant reached their maximum targeted dose.

3 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse events (AEs) and treatment emergent AEs (TEAEs) were collected from the time of screening (prior to start of study medication) until termination of the study.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Donepezil Hydrochloride	0 of 5 (0%)	2 of 5 (40%)	0 of 5
Placebo	0 of 3 (0%)	1 of 3 (33.3%)	0 of 3

Limitations and caveats (from the sponsor): This was a 10-week double blind placebo-controlled trial that was terminated early due to the results of a similarly-designed study showing it would be futile to continue this study.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Thomas McRae, MD study director

Pfizer

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Aricept (donepezil hydrochloride) in people with Down Syndrome and Cognitive Dysfunction, run by Eisai Inc. at 2 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 10 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: stopped early, as of the sponsor's last update on 23 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

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 23 Apr 2018). 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 Vineland-II Adaptive Behavior Scale (VABS-II) Parent/Caregiver Rating Form (PCRF) Score Using Last Observation Carried Forward (LOCF) (time frame: Baseline (Day 0) to Visit 3 (Week 10) or at early termination). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00754052.

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 23 Apr 2018.