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.

NCT02094053 | Completed Phase 2

• 1 other identifier: E2020-J081-345
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 10

Brief Summary

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.

Conditions

Down Syndrome

Keywords

Down syndrome; regression symptoms; disabled activities of daily living

Outcome Measures

Primary Outcomes (1)

• 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.

  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 Outcomes (2)

• Safety of E2020 and placebo in subjects with Down syndrome having regression and disabled ADL.

  Up to Week 28

• Pharmacokinetics (PK) of E2020 and placebo in subjects with Down syndrome having regression and disabled ADL

  Up to Week 28

Study Arms (3)

E2020 3 mg

EXPERIMENTAL

3 mg of E2020 (oral) once daily, for 24 weeks

Drug: E2020-Donepezil hydrochloride

E2020 5 mg

EXPERIMENTAL

5 mg of E2020 (oral) once daily, for 24 weeks

Drug: E2020-Donepezil hydrochloride

Placebo

PLACEBO COMPARATOR

placebo (oral) once daily, for 24 weeks

Drug: Placebo

Interventions

E2020-Donepezil hydrochloride DRUG

3 mg of E2020 (oral) once daily, for 24 weeks

E2020 3 mg

Placebo DRUG

placebo (oral) once daily, for 24 weeks

Placebo

Eligibility Criteria

• Age: 15 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (10)

Unknown Facility

Fukuoka, Fukuoka, Japan

Location

Unknown Facility

Sapporo, Hokkaido, Japan

Location

Unknown Facility

Yokohama, Kanagawa, Japan

Location

Unknown Facility

Takatsuki-shi, Kyoto, Japan

Location

Unknown Facility

Matsumoto-shi, Nagano, Japan

Location

Unknown Facility

Nagasaki, Nagasaki, Japan

Location

Unknown Facility

Izumi-shi, Osaka, Japan

Location

Unknown Facility

Saitama-shi, Saitama, Japan

Location

Unknown Facility

Chiyoda-ku, Tokyo, Japan

Location

Unknown Facility

Setagaya-ku, Tokyo, Japan

Location

MeSH Terms

Conditions

Down Syndrome

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2014
• First Posted: March 21, 2014
• Study Start: September 12, 2013
• Primary Completion: September 16, 2016
• Study Completion: April 21, 2017
• Last Updated: August 22, 2017

Record last verified: 2017-08

Locations

JP (10)