Clinical Trial Results:
A 10-Week, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Donepezil Hydrochloride (Aricept) in the Treatment of the Cognitive Dysfunction Exhibited by Children with Down Syndrome, Aged 6 to 10
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Summary
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EudraCT number |
2016-004949-92 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
10 Dec 2008
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Results information
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Results version number |
v1(current) |
This version publication date |
07 Apr 2019
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First version publication date |
07 Apr 2019
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Other versions |
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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-A001-336
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00754013 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Eisai Medical Services Inc.
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Sponsor organisation address |
100 Tice Boulevard, Woodcliff Lake, United States,
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Public contact |
Eisai Medical Information, Eisai Inc., 011 888247-2378, esi-medinfo@eisai.com
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Scientific contact |
Eisai Medical Information, Eisai Inc., 011 888247-2378, 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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
10 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 |
10 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 was to determine the efficacy and safety of donepezil hydrochloride (Aricept) in the treatment of cognitive dysfunction shown by children with Down syndrome, aged 6 to 10 years.
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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 |
06 Oct 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: 9
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Worldwide total number of subjects |
9
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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) |
9
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
0
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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 planned to recruit subjects at 26 centers in the United States. However, the study was terminated early and only 5 centers enrolled subjects during the period of 06 Oct 2008 to 10 Dec 2008. | ||||||||||||||||||
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Pre-assignment
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Screening details |
Due to early termination of the study by the Sponsor, only 9 participants were enrolled into the study. | ||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Donepezil HCl | ||||||||||||||||||
Arm description |
Donepezil was titrated to a dose of approximately 0.1-0.2 mg/kg/day as liquid containing 1 mg/1 mL of donepezil. | ||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||
Investigational medicinal product name |
Donepezil HCl
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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 |
Blinded oral donepezil hydrochloride (HCl), was started at 1.25 mL daily, followed by 2-week titration intervals over a period of 6 weeks until a maximum dose of 5 mg/kg/day or 10 mg/kg/day was reached. Due to early termination of the study, no participant reached either targeted maximum.
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Arm title
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Placebo | ||||||||||||||||||
Arm description |
Donepezil matched placebo was titrated in the similar way as the donepezil arm. | ||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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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 |
Participants received matching placebo in a 1:1:1 ratio.
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Baseline characteristics reporting groups
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Reporting group title |
Donepezil HCl
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Reporting group description |
Donepezil was titrated to a dose of approximately 0.1-0.2 mg/kg/day as liquid containing 1 mg/1 mL of donepezil. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Donepezil matched placebo was titrated in the similar way as the donepezil arm. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Donepezil HCl
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Reporting group description |
Donepezil was titrated to a dose of approximately 0.1-0.2 mg/kg/day as liquid containing 1 mg/1 mL of donepezil. | ||
Reporting group title |
Placebo
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Reporting group description |
Donepezil matched placebo was titrated in the similar way as the donepezil arm. | ||
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End point title |
Vineland-II Adaptive Behavior Scales (VABS-II) Parent/Caregiver Rating Form (PCRF) Sum of the 9 Sub-domain V-Scores (3 Scores for Each of the Communication, Daily Living Skills, And Socialization Domains) Using Last Observation Carried Forward [1] | ||||||||||||
End point description |
The primary objective of the study was evaluation of the efficacy and safety of donepezil hydrochloride in the treatment of the cognitive dysfunction exhibited by children with Down syndrome (DS), aged 6 to 10, as assessed by analysis of VABS-II/PCRF in the domains of communication, daily living skills, and socialization, and as assessed by standard safety measurements. The planned efficacy analysis was on the intent-to-treat (ITT) population. This study was terminated early. Primary efficacy data were not analyzed since only 9 of the 140 planned subjects had been enrolled.
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End point type |
Primary
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End point timeframe |
Visit 0 (Screen), Visits 1 (Baseline), 2, and 3 (or Early Termination)
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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: Due to early termination of the study, no analyses were performed. |
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| Notes [2] - This study was terminated early. Analyses were not performed. [3] - This study was terminated early. Analyses were not performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Mean Change From (Baseline) to Visit 3 (Week 10 or Early Termination) in VABS-II/PCRF Sum of The 9 Sub-domain V-Scores (3 Scores for Each of The Communication, Daily Living Skills, And Socialization Domains) Using Last Observation Carried Forward | ||||||||||||
End point description |
The planned secondary objectives of the study included further evaluation of efficacy as assessed by additional analyses of the VABS-II/PCRF, by analyses of the Test of Verbal Expression and Reasoning (TOVER), a subject-performance-based measure of expressive language function, and by the Forward Memory and Attention Sustained sub-tests of the Leiter International Performance Scale - Revised (Leiter-R), a cognitive assessment instrument for children and adolescents that is not language dependent. In addition, observed case analyses of these assessments at Week 4 and Week 10 were planned. This study was terminated early. Secondary efficacy data were not analyzed since only 9 of the 140 planned subjects had been enrolled.
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End point type |
Secondary
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End point timeframe |
Visit 1 (Baseline) to Visit 3 (Week 10 or early termination)
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| Notes [4] - This study was terminated early. Analyses were not performed. [5] - This study was terminated early. Analyses were not performed. |
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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 |
From date of first dose until 30 days after the last dose of study treatment, up to approximately 3 months.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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 |
Donepezil HCl
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Reporting group description |
Donepezil was titrated to a dose of approximately 0.1-0.2 mg/kg/day as liquid containing 1 mg/1 mL of donepezil. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Donepezil matched placebo was titrated in the similar way as the donepezil arm. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? No | |||
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. | |||
| Due to the study terminating early, only 9 subjects were enrolled and these subjects receive only limited exposure to study medications with no subject reaching his/her maximum targeted dose. Therefore, the planned efficacy criteria was not analyzed. | |||
