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.

Phase 2

Completed

• Conditions: Down Syndrome
• Interventions: Drug: E2020-Donepezil hydrochloride; Drug: Placebo

• Registration Number: NCT02094053
• Lead Sponsor: Eisai Co., Ltd.

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.

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 Timeline

• Study Start: 2013-09-12
• Study First Submitted: 2014-03-19
• Study First Submitted QC: 2014-03-19
• Study First Posted: 2014-03-21
• Primary Completion: 2016-09-16
• Study Completion: 2017-04-21
• Status Verified: 2017-08
• Last Update Submitted: 2017-08-21
• Last Update Posted: 2017-08-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 36

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
E2020 3 mg	E2020-Donepezil hydrochloride	3 mg of E2020 (oral) once daily, for 24 weeks
E2020 5 mg	E2020-Donepezil hydrochloride	5 mg of E2020 (oral) once daily, for 24 weeks
Placebo	Placebo	placebo (oral) once daily, for 24 weeks

Primary Outcome Measures

Name	Time	Method
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.	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.

Secondary Outcome Measures

Name	Time	Method
Safety of E2020 and placebo in subjects with Down syndrome having regression and disabled ADL.	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.
Pharmacokinetics (PK) of E2020 and placebo in subjects with Down syndrome having regression and disabled ADL	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.