Clinical Trial Results:
An Open-Label Study To Evaluate The Safety Of Donepezil Hydrochloride (Aricept) For Up To 1 Year In The Treatment Of The Cognitive Dysfunction Exhibited By Children With Down Syndrome - Follow-Up To A 10-Week, Double-Blind, Placebo-Controlled Trial
Summary
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EudraCT number |
2016-004947-35 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
15 Dec 2008
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Results information
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Results version number |
v1(current) |
This version publication date |
23 May 2021
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First version publication date |
23 May 2021
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
E2020-A001-220
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00675025 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Eisai Medical Research Inc.
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Sponsor organisation address |
100 Tice Boulevard, Woodcliff Lake, New Jersey, United States, 07677
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Public contact |
Eisai Medical Information, Eisai Inc., 888 274-2378, esi-medinfo@eisai.com
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Scientific contact |
Eisai Medical Information, Eisai Inc., 888 274-2378, esi-medinfo@eisai.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
15 Dec 2008
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
15 Dec 2008
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
The purpose of this study is to determine the safety of donepezil hydrochloride (Aricept) in children with Down syndrome who have finished the preceding 10-week, double-blind study of donepezil hydrochloride. Medical tests for drug safety will be conducted at each clinic visit.
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Protection of trial subjects |
This study was conducted in accordance with standard operating procedures (SOPs) of the sponsor (or designee), which are designed to ensure adherence to Good Clinical Practice (GCP) guidelines as required by the following: - Principles of the World Medical Association Declaration of Helsinki (World Medical Association, 2008) - International Council on Harmonisation (ICH) E6 Guideline for GCP (CPMP/ICH/135/95) of the European Agency for the Evaluation of Medicinal Products, Committee for Proprietary Medicinal Products, International Council for Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use - Title 21 of the United States (US) Code of Federal Regulations (US 21 CFR) regarding clinical studies, including Part 50 and Part 56 concerning informed subject consent and Institutional Review Board (IRB) regulations and applicable sections of US 21 CFR Part 312 - European Good Clinical Practice Directive 2005/28/EC and Clinical Trial Directive 2001/20/EC for studies conducted within any European Union (EU) country. All suspected unexpected serious adverse reactions were reported, as required, to the Competent Authorities of all involved EU member states. - Article 14, Paragraph 3, and Article 80-2 of the Pharmaceutical Affairs Law (Law No. 145, 1960) for studies conducted in Japan, in addition to Japan’s GCP Subject Information and Informed Consent.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
04 Apr 2008
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United States: 117
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Worldwide total number of subjects |
117
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
113
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Adults (18-64 years) |
4
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was recruited at 24 centers in the United States during the period of 04 Apr 2008 to 15 Dec 2008. All subjects who completed the double-blind (DB) placebo-controlled, 10 week study (Study 2020-A001-219 [NCT00570128]) were offered enrollment in this study. | ||||||||||||||||||||||||
Pre-assignment
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Screening details |
The Screening and baseline activities for this study took place on the same day as the Week 10 final visit of the double-blind (DB) study (2020-A001-219 [NCT00570128]). | ||||||||||||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Prior Donepezil-DB | ||||||||||||||||||||||||
Arm description |
Subjects who received donepezil in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Donepezil Hydrochloride
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Investigational medicinal product code |
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Other name |
Aricept
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Pharmaceutical forms |
Oral liquid
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received donepezil titrated to a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL.
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Arm title
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Prior Placebo-DB | ||||||||||||||||||||||||
Arm description |
Subjects who received matched placebo in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Donepezil Hydrochloride
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Investigational medicinal product code |
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Other name |
Aricept
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Pharmaceutical forms |
Oral liquid
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Routes of administration |
Oral use
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Dosage and administration details |
Subjects received donepezil titrated to a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL.
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Baseline characteristics reporting groups
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Reporting group title |
Prior Donepezil-DB
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Reporting group description |
Subjects who received donepezil in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prior Placebo-DB
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Reporting group description |
Subjects who received matched placebo in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Prior Donepezil-DB
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Reporting group description |
Subjects who received donepezil in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42. | ||
Reporting group title |
Prior Placebo-DB
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Reporting group description |
Subjects who received matched placebo in the double-blind study E2020-A001-219 (NCT00570128) were continued in this OLE study to be treated with donepezil titrated to achieve a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL for up to approximately Week 42. |
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End point title |
Change From Visit 1 (Baseline) to Visit 4 (or Early Termination) in the Vineland Adaptive Behavior Scales, 2nd Edition, Parent/Caregiver Rating Form (VABS-II/PCRF) Sum of the 9 Sub-domain V-scores [1] | ||||||||||||||||||
End point description |
VABS-II/PCRF assessed subject's adaptive behaviors on 3 domains (each has 3 sub-domains): Communication (receptive, expressive, written), Daily Living Skills (personal, domestic, community), Socialization (interpersonal relationships, play a leisure time, coping skills). Parent/caregiver rated subject's behavior for sub-domains from 0 (never present) to 2 (always present). Raw scores from sub-domains converted into standardized score(V-scale scores) ranged:1-24 for each sub-domain, mean=15,standard deviation(SD)=3,higher scores=higher level of adaptive functioning and were summed to obtain V-scale composite score ranged 9-216, mean=100,SD=15,higher scores=higher level of adaptive functioning, positive change=improvement in adaptive functioning. Composite and individual analyses, both raw and standardized scores, were not performed due to lack of significant differences between donepezil and placebo in parent study. Analyses was performed on the Intent-to-treat population.
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End point type |
Primary
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End point timeframe |
Visit 1 (Baseline); Visit 4 (Week 42)
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data were planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
Baseline up to early termination visit (Week 36)
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Adverse event reporting additional description |
Individual counts of non-serious adverse events (SAEs) were not available for this study, so the minimum number of events (i.e. the number of subject's experiencing an event) has been reported. Occurrences of non-SAEs may potentially have been higher than reported if one subject experienced the same event more than once.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
11.1
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Reporting groups
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Reporting group title |
Prior Donepezil-DB
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Reporting group description |
Subjects received donepezil titrated to a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Prior Placebo-DB
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Reporting group description |
Subjects received donepezil titrated to a final dose of 0.1 - 0.2 mg/kg/day using liquid formulated at 5 mg/5 mL. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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23 Jun 2008 |
The following administrative changes were identified and were made to the Protocol 111 Amendment 01 after the original (19 Dec 2007) protocol was finalized: 1. Header, footer, and title page changed to reflect new amendment date and version. 2. Pfizer Study Manager was changed (Protocol Sections 1.3 and 15). 3. Person's title was changed (Protocol Sections 1.3 and 15). 4. Typographic error in second paragraph corrected; changed from "will be given in a final protocol appendix" to "is in Appendix II" (Protocol Section 9.7). 5. Typographic error in last bullet point corrected; changed from "16 weeks" to "18 weeks" (Protocol Section 10.3 .5). 6. Concomitant medication list revised to reflect changes in concomitant medication allowed and not allowed during the study (Protocol Appendix II). |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
This was an open-label trial that was terminated early by the Sponsor. Sufficient evidence of efficacy not met. Discontinuation was not based on any safety concerns. |