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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
36

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

  • Japan
    • Fukuoka
      • Fukuoka-shi, Fukuoka, Japan
    • Hokkaido
      • Sapporo-shi, Hokkaido, Japan
    • Kanagawa
      • Yokohama-shi, Kanagawa, Japan
    • Kyoto
      • Takatsuki-shi, Kyoto, Japan
    • Nagano
      • Matsumoto-shi, Nagano, Japan
    • Nagasaki
      • Nagasaki-shi, Nagasaki, Japan
    • Osaka
      • Izumi-shi, Osaka, Japan
    • Saitama
      • Saitama-shi, Saitama, Japan
    • Tokyo
      • Chiyoda-ku, Tokyo, Japan
      • Setagaya-ku, Tokyo, Japan

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

11 years to 35 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

At enrollment in Pre-randomization Phase

  1. With definitive diagnosis of Down syndrome
  2. 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
  3. Insufficiently improved with environmental adjustment and psychotherapies including counseling for greater than or equal to 8 weeks before enrollment
  4. 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.
  5. A total score of Body Functionality Checklist (51 items) is lesser than or equal to 210 at enrollment
  6. Aged 15 to 39 years inclusive
  7. Males and females
  8. 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
  9. Males and females of childbearing potential must practice highly effective contraception
  10. Able to comply with scheduled study visits according to the investigator's instruction
  11. Able to visit for scheduled assessments (except for walking difficulty due to development of regression)
  12. 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

  1. 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).
  2. 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
  3. Previously diagnosed with autism
  4. With evidence of atlantoaxial subluxation, or underwent surgical operation for atlantoaxial subluxation within 2 years
  5. Have seizure symptoms within 2 years or used antiepileptic drug within 1 year before enrollment of Pre-randomization Phase.
  6. With severe hearing or visual impairment which may affect regression
  7. 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
  8. Have a complication of clinically significant active and unstable diseases in the gastrointestinal, hepatic, renal, respiratory, or cardiovascular system
  9. Have a history of clinically significant gastrointestinal ulcer, bronchial asthma, or obstructive pulmonary disease
  10. 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)
  11. With a present or past history of malignant tumor within 5 years before informed consent (except for basal cell carcinoma, squamous cell carcinoma)
  12. With a complication or history of drug or alcohol dependency within recent 10 years
  13. Have a known hypersensitivity to ingredient(s) of donepezil hydrochloride or peperidine derivatives
  14. 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
  15. Pregnant or lactating women
  16. Have participated in another clinical study and received the study drug within 12 weeks before the enrollment of this study
  17. Have used donepezil hydrochloride or have participated in a clinical study of E2020 and received E2020 in the past
  18. With a history of a treatment for Alzheimer's type dementia

  19. With severe extrapyramidal disorder

    At enrollment in the Double-blind Phase

  20. 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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: E2020 3 mg
3 mg of E2020 (oral) once daily, for 24 weeks
Drug: E2020-Donepezil hydrochloride
3 mg of E2020 (oral) once daily, for 24 weeks
Drug: E2020-Donepezil hydrochloride
5 mg of E2020 (oral) once daily, for 24 weeks
Experimental: E2020 5 mg
5 mg of E2020 (oral) once daily, for 24 weeks
Drug: E2020-Donepezil hydrochloride
3 mg of E2020 (oral) once daily, for 24 weeks
Drug: E2020-Donepezil hydrochloride
5 mg of E2020 (oral) once daily, for 24 weeks
Placebo Comparator: Placebo
placebo (oral) once daily, for 24 weeks
Drug: Placebo
placebo (oral) once daily, for 24 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
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.
Baseline to Week 12 and Week 24

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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
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.
Up to Week 28
Pharmacokinetics (PK) of E2020 and placebo in subjects with Down syndrome having regression and disabled ADL
Time Frame: Up to Week 28
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.
Up to Week 28

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eisai Co., Ltd.

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 12, 2013

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 16, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 21, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 19, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 19, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 21, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
August 22, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 21, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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