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 11 To 17
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Summary
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EudraCT number |
2016-004948-11 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
11 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-A001-335
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00754052 | ||
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 |
11 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 |
11 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 the cognitive dysfunction shown by children with Down syndrome, aged 11 to 17.
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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 |
30 Sep 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: 8
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Worldwide total number of subjects |
8
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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) |
8
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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 |
- | |||||||||||||||
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Pre-assignment
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Screening details |
Due to early termination of the study by the Sponsor, only 8 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 |
Blinded oral donepezil HCl, was started at 2.5 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. | |||||||||||||||
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 2.5 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 |
Participants received matching placebo in a 1:1:1 ratio. | |||||||||||||||
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 |
Blinded oral donepezil HCl, was started at 2.5 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. | ||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received matching placebo in a 1:1:1 ratio. | ||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Donepezil HCl
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Reporting group description |
Blinded oral donepezil HCl, was started at 2.5 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. | ||
Reporting group title |
Placebo
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Reporting group description |
Participants received matching placebo in a 1:1:1 ratio. | ||
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End point title |
Mean Change from Baseline in Vineland-II Adaptive Behavior Scale (VABS-II) Parent/Caregiver Rating Form (PCRF) Score Using Last Observation Carried Forward (LOCF) [1] | ||||||||||||
End point description |
VABS-II/PCRF assesses the social abilities of an individual in the age range of preschool to 18 years old. The test measures 5 main domains; (Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior (optional)), each with 2-3 subdomains. It is in the form of a questionnaire and administered as a semi-structured interview. Each item is rated on a scale of 0 to 2, along with the codes ("N") for instances when the child has never had the opportunity to perform the activity, and a code ("DK") when the caregiver does not know if the child performed the activity. Sum-domain raw scores are obtained by summing the numerical values of the responses then compared to a table in the manual to obtain a standard score (with a mean of 100 and standard deviation of 15), percentile ranks, stanines, and age equivalents. The plan for this trial was to include 3 scores for each of the domains, communication, daily living skills, and socialization domains.
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End point type |
Primary
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End point timeframe |
Baseline (Day 0) to Visit 3 (Week 10) or at 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, analyses were not 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 in Additional Analyses of the VABS-11/PCRF Sustained sub-tests of the Leiter-R | ||||||||||||
End point description |
Additional analyses were to be performed using the VABS-II/PCRF test, (as described in the primary outcome section of this document). In addition, observed cases analyses of these assessments at Week 4 and Week 10 were planned. Efficacy data were collected on the 8 participants already enrolled in the study at the time of early termination. Analyses were not performed due to study medication exposure being limited and variable, limited efficacy data were collected, and no participant reached their maximum targeted dose.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) 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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End point title |
Mean Change from Baseline in Test of Verbal Expression and Reasoning (TOVER) | ||||||||||||
End point description |
Additional analyses were to be performed using the TOVER test. In addition, observed cases analyses of these assessments at Week 4 and Week 10 were planned. Efficacy data were collected on the 8 participants already enrolled in the study at the time of early termination. Analyses were not performed due to study medication exposure being limited and variable, limited efficacy data were collected, and no participant reached their maximum targeted dose.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) to Visit 3 (Week 10) or early termination
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| Notes [6] - This study was terminated early. Analyses were not performed. [7] - 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 if the Forward Memory and Attention Sustained Sub-tests of the Leiter-R | ||||||||||||
End point description |
Additional analyses were to be performed using the Forward Memory and Attention Sustained sub-tests of the Leiter-R (revised scale). In addition, observed cases analyses of these assessments at Week 4 and Week 10 were planned. Efficacy data were collected on the 8 participants already enrolled in the study at the time of early termination. Analyses were not performed due to study medication exposure being limited and variable, limited efficacy data were collected, and no participant reached their maximum targeted dose.
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End point type |
Secondary
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End point timeframe |
Baseline (Day 0) to Visit 3 (Week 10) or early termination
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| Notes [8] - This study was terminated early. Analyses were not performed. [9] - 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 |
Adverse events (AEs) and treatment emergent AEs (TEAEs) were collected from the time of screening (prior to start of study medication) until termination of the study.
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Adverse event reporting additional description |
The Safety Population included all 8 participants who received at least 1 dose of study medication.
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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 |
Blinded oral donepezil HCl, was started at 2.5 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. | ||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Participants received matching placebo in a 1:1:1 ratio. | ||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||
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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. | |||
| This 10-week double blind placebo-controlled trial was terminated early after the results of a similarly-designed study showing lack of effect and therefore there was no benefit to continue this study. | |||
