- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02094053
A Double-blind, Placebo-controlled Comparative Study and Open-label Extension Study to Confirm the Efficacy and Safety of E2020 in Subjects With Down Syndrome Having Regression Symptoms and Disabled Activities of Daily Living.
August 21, 2017 updated by: Eisai Co., Ltd.
The purpose of this double-blind, placebo-controlled, comparative study and open-label extension study is to confirm the efficacy and safety of E2020 in subjects with Down syndrome having regression symptoms and disabled activities of daily living.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
This is a multicenter, randomized, double-blind, multiple-dose (two doses), placebo-controlled, parallel-group comparative study followed by an open-label extension study of E2020 in subjects with Down syndrome having regression and disabled ADL.
A total of 60 subjects will be randomized to one of three dosing groups (at 1:1:1) to receive 3 mg of E2020, 5 mg of E2020, or placebo for 24 weeks based on their total scores of Body Functionality Checklist, sex, and study site as the allocation factors.
This study consists of Pre-randomization Phase (4 weeks), Double-blind Phase (28 weeks), and Extension Phase (24 weeks).
The Double-blind Phase includes a 24-week treatment period plus a 4-week transition period.
Study Type
Interventional
Enrollment (Actual)
36
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Fukuoka
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Fukuoka-shi, Fukuoka, Japan
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Hokkaido
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Sapporo-shi, Hokkaido, Japan
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Kanagawa
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Yokohama-shi, Kanagawa, Japan
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Kyoto
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Takatsuki-shi, Kyoto, Japan
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Nagano
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Matsumoto-shi, Nagano, Japan
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Nagasaki
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Nagasaki-shi, Nagasaki, Japan
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Osaka
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Izumi-shi, Osaka, Japan
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Saitama
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Saitama-shi, Saitama, Japan
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Tokyo
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Chiyoda-ku, Tokyo, Japan
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Setagaya-ku, Tokyo, Japan
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
13 years to 37 years (Child, Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria
At enrollment in Pre-randomization Phase
- With definitive diagnosis of Down syndrome
- Have greater than or equal to 3 of the following 4 symptoms among 9 items according to the diagnostic criteria issued by the Intractable Diseases Treatment Research Program 2010 (Research paper on Intractable Diseases Treatment Research Program; Survey on Sudden Regression (21 trisomy) and Preparation of Diagnostic Criteria.) Motor retardation, mutism, social withdrawal (homeboundness), sleep disorder
- Insufficiently improved with environmental adjustment and psychotherapies including counseling for greater than or equal to 8 weeks before enrollment
- Have a suspected diagnosis with neuropsychiatric disorder without sufficient effect on a disease even after medical treatment for greater than or equal to 8 weeks before enrollment.
- A total score of Body Functionality Checklist (51 items) is lesser than or equal to 210 at enrollment
- Aged 15 to 39 years inclusive
- Males and females
- Must have a family member or a caregiver who will provide written informed consent and will be able to spend 3 days a week with the subject (at least 4 hours per day) and will be able to support the subject during the study by providing necessary study information to the subject, assisting treatment compliance, and accompanying the subject to all scheduled visits, supporting study-related tests for the efficacy and safety assessments throughout the study period
- Males and females of childbearing potential must practice highly effective contraception
- Able to comply with scheduled study visits according to the investigator's instruction
- Able to visit for scheduled assessments (except for walking difficulty due to development of regression)
- Submitted written informed consent for study entry (to obtain from subjects as much as possible; mandatory from their legal guardian)
Exclusion Criteria
At enrollment in Pre-randomization Phase
- Suspected to have progressive neuropsychiatric disease (e.g., neurodegenerative disorder and progressive tumor) evidenced by MRI or CT within 1 year before the Pre-randomization Phase (if not tested within 1 year before the Pre-randomization Phase, reconfirm during the Pre-randomization Phase).
- Have a history of significant neurological disorders such as stroke, brain tumor, encephalitis, meningitis, normal pressure hydrocephalus, brain trauma accompanying unconsciousness, and experience of brain surgery causing unsolved deficiency
- Previously diagnosed with autism
- With evidence of atlantoaxial subluxation, or underwent surgical operation for atlantoaxial subluxation within 2 years
- Have seizure symptoms within 2 years or used antiepileptic drug within 1 year before enrollment of Pre-randomization Phase.
- With severe hearing or visual impairment which may affect regression
- Have a complication of cardiac disease (angina pectoris, congestive heart failure, bundle branch block, arrythmia) or peripheral vascular disease with unstable condition in 3 months before enrollment of Pre-randomization Phase
- Have a complication of clinically significant active and unstable diseases in the gastrointestinal, hepatic, renal, respiratory, or cardiovascular system
- Have a history of clinically significant gastrointestinal ulcer, bronchial asthma, or obstructive pulmonary disease
- Have a complication of disease affecting absorption, distribution, and metabolism of study drug (e.g., inflammatory colon disease, gastric ulcer, duodenal ulcer, hepatic disorder, serious lactose intolerance)
- With a present or past history of malignant tumor within 5 years before informed consent (except for basal cell carcinoma, squamous cell carcinoma)
- With a complication or history of drug or alcohol dependency within recent 10 years
- Have a known hypersensitivity to ingredient(s) of donepezil hydrochloride or peperidine derivatives
- Not meet the criteria of prohibited and restricted concomitant medications, or anticipated to deviate from the above criteria of prohibited and restricted concomitant medications/therapies during the study
- Pregnant or lactating women
- Have participated in another clinical study and received the study drug within 12 weeks before the enrollment of this study
- Have used donepezil hydrochloride or have participated in a clinical study of E2020 and received E2020 in the past
- With a history of a treatment for Alzheimer's type dementia
With severe extrapyramidal disorder
At enrollment in the Double-blind Phase
- Suspected to have a complication of severe disease considering from the laboratory parameters at enrollment in the Pre-randomization Phase (visit 1) and the safety is not protected in the opinion of the principal investigator or subinvestigator
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
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 |
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Experimental: E2020 3 mg
3 mg of E2020 (oral) once daily, for 24 weeks
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3 mg of E2020 (oral) once daily, for 24 weeks
5 mg of E2020 (oral) once daily, for 24 weeks
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Experimental: E2020 5 mg
5 mg of E2020 (oral) once daily, for 24 weeks
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3 mg of E2020 (oral) once daily, for 24 weeks
5 mg of E2020 (oral) once daily, for 24 weeks
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Placebo Comparator: Placebo
placebo (oral) once daily, for 24 weeks
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placebo (oral) once daily, for 24 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in total scores from baseline using Body Functionality Checklist (psychosomatic function questionnaire) in subjects with Down syndrome having regression symptoms and disabled activities of daily living (ADL), relative to placebo.
Time Frame: Baseline to Week 12 and Week 24
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For the changes in a total score of Body Functionality Checklist (51 items) from Week 0 of the treatment period, Kruskal-Wallis test will be performed in the 3 mg group, the 5 mg group and placebo group to represent statistical significance.
Summary statistics of the total score of Body Functionality Checklist (51 items) at each evaluation time and changes from before study drug administration in the treatment period will be calculated by dose group.
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Baseline to Week 12 and Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety of E2020 and placebo in subjects with Down syndrome having regression and disabled ADL.
Time Frame: Up to Week 28
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The safety will be measured by frequencies of treatment-emergent adverse events (TEAEs) in the treatment period, statistics of laboratory parameters, blood pressure, and pulse rate at each evaluation time and changes from before study drug administration, and 12-lead ECG assessment, frequency distribution (yes/no) at each evaluation time will be collected and the percent (%) will be calculated by dose group.
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Up to Week 28
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Pharmacokinetics (PK) of E2020 and placebo in subjects with Down syndrome having regression and disabled ADL
Time Frame: Up to Week 28
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Population PK analysis will be performed to build PK models to explain plasma donepezil hydrochloride concentration data.
In addition, the models may be used to explore relationship of PK data with demographics, efficacy, and AEs.
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Up to Week 28
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
September 12, 2013
Primary Completion (Actual)
September 16, 2016
Study Completion (Actual)
April 21, 2017
Study Registration Dates
First Submitted
March 19, 2014
First Submitted That Met QC Criteria
March 19, 2014
First Posted (Estimate)
March 21, 2014
Study Record Updates
Last Update Posted (Actual)
August 22, 2017
Last Update Submitted That Met QC Criteria
August 21, 2017
Last Verified
August 1, 2017
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Nervous System Diseases
- Neurologic Manifestations
- Neurobehavioral Manifestations
- Disease
- Congenital Abnormalities
- Genetic Diseases, Inborn
- Intellectual Disability
- Abnormalities, Multiple
- Chromosome Disorders
- Syndrome
- 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-J081-345
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.
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