Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Randomized, Double-Blind, Placebo-Controlled Study of Efficacy and Safety of Donepezil Hydrochloride in Preadolescent and Adolescent Children with Attention Impairment Following Cancer Treatment

    Summary
    EudraCT number
    		 2007-005435-28
    Trial protocol
    		 GB   ES   NL   FR   DE  
    Global end of trial date
    18 Sep 2009

    Results information
    Results version number
    		 v1
    This version publication date
    29 Jul 2016
    First version publication date
    29 Jul 2016
    Other versions
    		 v2

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    E2020-G000-333
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00688376
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Eisai
    Sponsor organisation address
    100 Tice Boulevard, Woodcliff Lake, United States, 07677
    Public contact
    Eisai Call Center, Eisai Inc., 888 422-4743,
    Scientific contact
    Eisai Call Center, Eisai Inc., 888 422-4743,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    18 Sep 2009
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    26 May 2009
    Global end of trial reached?
    Yes
    Global end of trial date
    18 Sep 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to evaluate the efficacy, safety and tolerability of donepezil in children with persistent attention impairment that is present at least 12 months after the completion of cancer treatment.
    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 Conference 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 Conference on Harmonisation 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.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Aug 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Spain: 4
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    France: 11
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Argentina: 1
    Country: Number of subjects enrolled
    Australia: 2
    Country: Number of subjects enrolled
    Chile: 4
    Country: Number of subjects enrolled
    United States: 33
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Canada: 1
    Country: Number of subjects enrolled
    South Africa: 9
    Worldwide total number of subjects
    71
    EEA total number of subjects
    21
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    22
    Adolescents (12-17 years)
    49
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Out of 59 participants who entered the blinded extension phase, 49 participants completed and 10 participants discontinued the extension phase. Reasons for participant discontinuation was as follows: adverse event (7); withdrawal of consent (1); physician decision (1); and not specified (1).

    Pre-assignment
    Screening details
    		 This trial had three phases: (1) pre-randomization to establish eligibility; (2) a 12-week, double-blind, placebo-controlled, parallel-group phase with dose escalation based on body weight; (3) a 12-week, blinded extension phase during which all subjects received active drug. Eligible subjects were randomized to receive placebo or donepezil.

    Period 1
    Period 1 title
    Double-Blind Phase (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator
    Blinding implementation details
    During the Blinded Extension Phase, study personnel, participants, and parents/legal guardians continued to be blinded to the treatment that each participant received during the preceding Double-Blind Phase.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Donepezil
    Arm description
    		 Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily
    Arm type
    		 Experimental

    Investigational medicinal product name
    Donepezil
    Investigational medicinal product code
    Other name
    Aricept, E2020
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    During the Double-Blind Phase, all participants randomized to receive donepezil started on 3 mg/day. Participants who weighed 35 to 49.9 kg were titrated up to 5 mg/day final dose three weeks later. Participants weighing 50.0 kg or more were titrated up after three weeks to 5 mg/day, then to a final dose of 10 mg/day three week later. No down-titrations were allowed. At Week 12, the Double-Blind Phase ended, and the Blinded Extension Phase began. Participants who were randomized to receive active treatment during the Double-Blind Phase remained at the same dose level during the entire Blinded Extension Phase.

    Arm title
    		 Placebo
    Arm description
    		 Placebo, matching 3 mg, 5 mg, or 10 mg placebo tablets administered orally, once daily
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    During the Double-Blind Phase, matching 3 mg, 5 mg, and 10 mg placebo tablets were administered orally, once daily, to participants receiving placebo. At Week 12, the Double-Blind Phase ended, and the Blinded Extension Phase began. Participants who had been on placebo during the Double-Blind Phase began receiving active treatment during the Blinded Extension Phase. Dose titration was applied for those participants on final doses of 5 mg and 10 mg donepezil, according to the dose increment (titration) schedule that was applied to active treatment participants during the Double-Blind Phase.

    Number of subjects in period 1
    		Donepezil Placebo
    Started
    40
    31
    Completed
    34
    25
    Not completed
    6
    6
         Consent withdrawn by subject
    1
    -
         Adverse event, non-fatal
    4
    4
         Protocol violation
    1
    2

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Donepezil
    Reporting group description
    		 Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo, matching 3 mg, 5 mg, or 10 mg placebo tablets administered orally, once daily

    Reporting group values
    		 Donepezil Placebo Total
    Number of subjects
    		 40 31 71
    Age categorical
    Units: Subjects
        In utero
    		 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0
        Newborns (0-27 days)
    		 0
        Infants and toddlers (28 days-23 months)
    		 0
        Children (2-11 years)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 12.1 ± 3.06 11.6 ± 2.83 -
    Gender categorical
    Units: Subjects
        Female
    		 15 21 36
        Male
    		 25 10 35

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Donepezil
    Reporting group description
    		 Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily

    Reporting group title
    Placebo
    Reporting group description
    		 Placebo, matching 3 mg, 5 mg, or 10 mg placebo tablets administered orally, once daily

    Primary: Change From Baseline in the Test of Variables in Attention-Continuous Performance Test (TOVA-CPT) "d-prime" Standard Score (SS) at Week 12

    		 Close Top of page
    End point title
    		 Change From Baseline in the Test of Variables in Attention-Continuous Performance Test (TOVA-CPT) "d-prime" Standard Score (SS) at Week 12
    End point description
    The TOVA-CPT test has a standardized computer game-like format that tests attention and simple impulse control. It precisely measures a person’s reaction time to clicking on correct targets versus incorrect targets. Scores are based on the number of "Hits" (correct responses), omission errors (failure to respond), commission errors/”False Alarms” (incorrect responses), response time, and sensitivity ("d-prime"). “D-prime” is a measure of distractibility and reflects how well a person reacts correctly versus incorrectly. A higher value of "d-prime" is reached by having more "Hits" (correct response) and fewer "False Alarms" (incorrect response). Analysis was based on three factors: the “d-prime” standard score, the reaction time variability standard score, and the response time standard score. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.
    End point type
    Primary
    End point timeframe
    Visit 0 (Screening) and Week 12 (Visit 4)
    End point values
    		 Donepezil Placebo
    Number of subjects analysed
    39
    30
    Units: "d-prime"
        arithmetic mean (standard deviation)
    5.2 ± 8.77
    4.5 ± 7.39
    Statistical analysis title
    		 Change from Baseline in "d-prime" SS at Week 12
    Statistical analysis description
    P-values, least squares (LS) mean, and 95% confidence interval (CI) were obtained from Analysis of Covariance (ANCOVA) model with treatment group as a factor and Baseline value as covariate.
    Comparison groups
    Placebo v Donepezil
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.694
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.22
         upper limit
    		 4.8

    Secondary: Change From Baseline at Week 6 or Week 12 in the TOVA-CPT "d-prime" Standard Score (SS)

    		 Close Top of page
    End point title
    		 Change From Baseline at Week 6 or Week 12 in the TOVA-CPT "d-prime" Standard Score (SS)
    End point description
    The TOVA-CPT test has a standardized computer game-like format that tests attention and simple impulse control. It precisely measures a person’s reaction time to clicking on correct targets versus incorrect targets. Scores are based on the number of "Hits" (correct responses), omission errors (failure to respond), commission errors/”False Alarms” (incorrect responses), response time, and sensitivity ("d-prime"). “D-prime” is a measure of distractibility and reflects how well a person reacts correctly versus incorrectly. A higher value of "d-prime" is reached by having more "Hits" (correct response) and fewer "False Alarms" (incorrect response). Analysis was based on three factors: the “d-prime” standard score, the reaction time variability standard score, and the response time standard score. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.
    End point type
    Secondary
    End point timeframe
    Screening (Visit 0) and Week 6, and Week 12
    End point values
    		 Donepezil Placebo
    Number of subjects analysed
    39
    30
    Units: "d-prime"
        arithmetic mean (standard deviation)
    5.7 ± 8.41
    6.2 ± 9.49
    Statistical analysis title
    		 Change from Baseline at Week 6 or Week 12
    Statistical analysis description
    P-values, LS mean, and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9458
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.38
         upper limit
    		 4.09

    Secondary: Change From Baseline at Week 6 or Week 12 in the Reaction Time Variability Standard Score (RTVSS) and Response Time Standard Score (RTSS)

    		 Close Top of page
    End point title
    		 Change From Baseline at Week 6 or Week 12 in the Reaction Time Variability Standard Score (RTVSS) and Response Time Standard Score (RTSS)
    End point description
    The Reaction Time Variability is defined as the time measurement of how consistently the switch is pressed. The Response Time is the measurement of how fast or slow information is processed and responded to by the participant. The testing process was as described in a previous outcome measure. Standard scores less than or equal to 80 were significant for an attention deficit disorder. Standard scores greater than 80 were not significant for an attention deficit disorder.
    End point type
    Secondary
    End point timeframe
    Screening (Visit 0) and Week 6, and Week 12
    End point values
    		 Donepezil Placebo
    Number of subjects analysed
    39
    30
    Units: Milliseconds
    arithmetic mean (standard deviation)
        RTVSS (Week 6)
    -3.4 ± 18.44
    -3.2 ± 15.75
        RTVSS (Week 12)
    -3.9 ± 15.21
    -5 ± 17
        RTSS (Week 6)
    -6.9 ± 13.17
    -9.6 ± 13.25
        RTSS (Week 12)
    -9 ± 13.15
    -9.1 ± 12.79
    Statistical analysis title
    		 RTVSS Change from Baseline to Week 6 (LOCF)
    Statistical analysis description
    P-values, LS mean, and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.743
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.56
         upper limit
    		 6.85
    Statistical analysis title
    		 RTVSS Change from Baseline to Week 12 (LOCF)
    Statistical analysis description
    P-values, LS mean, and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9561
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.42
         upper limit
    		 7.84
    Statistical analysis title
    		 RTSS Change from Baseline to Week 6 (LOCF)
    Statistical analysis description
    P-values, LS means, and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4385
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.97
         upper limit
    		 9.04
    Statistical analysis title
    		 RTSS Change from Baseline to Week 12 (LOCF)
    Statistical analysis description
    P-values, LS mean, and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9088
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    -0.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.74
         upper limit
    		 6

    Secondary: Change From Baseline in the Global Executive Composite Score, Behavioral Regulation Index, Metacognition Index, and Working Memory Subscale

    		 Close Top of page
    End point title
    		 Change From Baseline in the Global Executive Composite Score, Behavioral Regulation Index, Metacognition Index, and Working Memory Subscale
    End point description
    The Behavioral Rating Inventory of Executive Functioning (BRIEF) test evaluates impairment of executive function (planning and organization), memory, and sustained attention in children aged 5-18 years with a wide range of developmental and acquired neurological conditions. The survey is designed to assess the parent/guardian’s perception of their child’s executive functioning in home and school environments, which relate to daily function (as judged by the parent). Each survey contains 86 items that are scored as; 1 (the behavior is never a problem), 2 (the behavior is sometimes a problem), or 3 (the behavior is often a problem). Data was presented as the Global Executive Composite Score (range 72-216), Behavioral Regulation Index (range 28-84; inhibit, shift, and emotional control), Metacognition Index (range 44-132; initiate, working memory, plan/organize, organization of materials, and monitor), and Working Memory Subscale. Higher BRIEF scores indicate a decline in performance.
    End point type
    Secondary
    End point timeframe
    Baseline (Visit 1), Week 12 (Visit 4)
    End point values
    		 Donepezil Placebo
    Number of subjects analysed
    39
    30
    Units: Scores on a scale
    arithmetic mean (standard deviation)
        Global Executive Composite Score
    -1.3 ± 6.73
    -3.8 ± 6.78
        Behavioral Regulation Index
    0.8 ± 7.54
    -1.9 ± 6.91
        Metacognition Index
    -2.3 ± 7.29
    -4.9 ± 6.99
        Working Memory Scale
    -3.6 ± 7.45
    -3.3 ± 6.59
    Statistical analysis title
    		 Global Executive Composite Score Analysis
    Statistical analysis description
    P-values, LS mean, and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2886
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 4.96
    Statistical analysis title
    		 Behavioral Regulation Index Analysis
    Statistical analysis description
    P-values, LS mean, and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2555
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.54
         upper limit
    		 5.69
    Statistical analysis title
    		 Metacognition Index Analysis
    Statistical analysis description
    P-values and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3155
    Method
    		 ANCOVA
    Parameter type
    		 LS mean difference
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.63
         upper limit
    		 4.99
    Statistical analysis title
    		 Working Memory Scale Analysis
    Statistical analysis description
    P-values, LS mean, and 95% confidence intervals were obtained from ANCOVA model with treatment group as a factor and baseline value as covariate.
    Comparison groups
    Donepezil v Placebo
    Number of subjects included in analysis
    69
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9075
    Method
    		 ANCOVA
    Parameter type
    		 Least squares mean difference
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.55
         upper limit
    		 3.16

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    For each participant, adverse events were collected from the time the participant signed the informed consent form up to 30 days after discontinuation, or approximately 212 days.
    Adverse event reporting additional description
    Safety population included randomized participants who received at least one dose of study medication and who had at least one post-Baseline safety assessment. Treatment-emergent adverse events (TEAEs), defined as an adverse event that started/increased in severity on/after the first dose of study medication are presented in this section.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    11.0
    Reporting groups
    Reporting group title
    Donepezil Double-Blind Phase
    Reporting group description
    		 Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily

    Reporting group title
    Placebo Double-Blind Phase
    Reporting group description
    		 Placebo, matching 3 mg, 5 mg, or 10 mg placebo tablets administered orally, once daily

    Reporting group title
    Donepezil Blinded Extension Phase
    Reporting group description
    		 Donepezil 3 mg, 5 mg, or 10 mg donepezil Immediate Release (IR) orally, once daily

    Reporting group title
    Placebo Blinded Extension Phase
    Reporting group description
    		 Placebo, matching 3 mg, 5 mg, or 10 mg placebo tablets administered orally, once daily

    Serious adverse events
    		 Donepezil Double-Blind Phase Placebo Double-Blind Phase Donepezil Blinded Extension Phase Placebo Blinded Extension Phase
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
    1 / 25 (4.00%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Rhabdomyosarcoma
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Neutropenia
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 31 (0.00%)
    0 / 34 (0.00%)
    0 / 25 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 40 (0.00%)
    0 / 31 (0.00%)
    0 / 34 (0.00%)
    1 / 25 (4.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Donepezil Double-Blind Phase Placebo Double-Blind Phase Donepezil Blinded Extension Phase Placebo Blinded Extension Phase
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    25 / 40 (62.50%)
    17 / 31 (54.84%)
    11 / 34 (32.35%)
    13 / 25 (52.00%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    1 / 40 (2.50%)
    0 / 31 (0.00%)
    0 / 34 (0.00%)
    4 / 25 (16.00%)
         occurrences all number
    1
    0
    0
    4
    Headache
         subjects affected / exposed
    10 / 40 (25.00%)
    7 / 31 (22.58%)
    2 / 34 (5.88%)
    6 / 25 (24.00%)
         occurrences all number
    11
    11
    2
    10
    Memory impairment
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 31 (0.00%)
    0 / 34 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    0
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    2 / 40 (5.00%)
    3 / 31 (9.68%)
    2 / 34 (5.88%)
    0 / 25 (0.00%)
         occurrences all number
    2
    3
    2
    0
    Pyrexia
         subjects affected / exposed
    1 / 40 (2.50%)
    2 / 31 (6.45%)
    0 / 34 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    1
    2
    0
    0
    Asthenia
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 31 (6.45%)
    1 / 34 (2.94%)
    1 / 25 (4.00%)
         occurrences all number
    0
    2
    1
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    3 / 40 (7.50%)
    3 / 31 (9.68%)
    1 / 34 (2.94%)
    2 / 25 (8.00%)
         occurrences all number
    4
    3
    1
    4
    Abdominal pain upper
         subjects affected / exposed
    2 / 40 (5.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
    1 / 25 (4.00%)
         occurrences all number
    2
    2
    2
    1
    Diarrhoea
         subjects affected / exposed
    3 / 40 (7.50%)
    1 / 31 (3.23%)
    2 / 34 (5.88%)
    0 / 25 (0.00%)
         occurrences all number
    3
    1
    2
    0
    Nausea
         subjects affected / exposed
    7 / 40 (17.50%)
    2 / 31 (6.45%)
    1 / 34 (2.94%)
    3 / 25 (12.00%)
         occurrences all number
    9
    2
    1
    5
    Stomach discomfort
         subjects affected / exposed
    0 / 40 (0.00%)
    2 / 31 (6.45%)
    0 / 34 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    0
    2
    0
    0
    Vomiting
         subjects affected / exposed
    2 / 40 (5.00%)
    1 / 31 (3.23%)
    2 / 34 (5.88%)
    3 / 25 (12.00%)
         occurrences all number
    2
    1
    2
    3
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    4 / 40 (10.00%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    4
    1
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 40 (0.00%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    0
    1
    0
    3
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    3 / 40 (7.50%)
    2 / 31 (6.45%)
    0 / 34 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    3
    2
    0
    0
    Musculoskeletal and connective tissue disorders
    Muscle spasms
         subjects affected / exposed
    4 / 40 (10.00%)
    1 / 31 (3.23%)
    0 / 34 (0.00%)
    2 / 25 (8.00%)
         occurrences all number
    4
    1
    0
    3
    Pain in extremity
         subjects affected / exposed
    2 / 40 (5.00%)
    0 / 31 (0.00%)
    0 / 34 (0.00%)
    0 / 25 (0.00%)
         occurrences all number
    2
    0
    0
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    4 / 40 (10.00%)
    3 / 31 (9.68%)
    2 / 34 (5.88%)
    0 / 25 (0.00%)
         occurrences all number
    4
    3
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 40 (2.50%)
    1 / 31 (3.23%)
    2 / 34 (5.88%)
    1 / 25 (4.00%)
         occurrences all number
    1
    1
    2
    1

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Mar 2008
    Changes to the study design and conduct included: • Updated the number of centers to be approximately 40. • Updated the list of abbreviations and definition of terms. • Added information pertaining to pharmacokinetics and safety of donepezil in pediatric subjects. • Revised the secondary objectives of the study. • Revised inclusion criteria #2, #3, #7 and #14. • Renumbered the exclusion criteria and revised criteria #3, #6, #7 and #10. • Added exclusion criteria #4 stating exclusion of subjects scoring higher than the t-score of 75 on oppositional scale of CPRS-R(S). • Added exclusion criteria #17 stating exclusion of subjects diagnosed with Attention Deficit Hyperactivity Disorder (DSM IV criteria) before or after cancer therapy. • Added that the dose to be received by each subject was to be based on body weight at Screening. • Added Conners’ Parent Rating Scale – Revised (S). • Added section pertaining to warnings and precautions. Administrative changes included changes in Eisai contact information, and information about contract research organizations.
    25 Feb 2009
    Changes to the study design and conduct included: • Updated the number of centers to be approximately 50, and eliminated the use of centers in East Asia. • Revised the number of subjects from 300 to 70 and noted that data from studies E2020-G000-333 and E2020-G000-334 would be pooled. • Revised the TOVA-CPT measure to be used as the primary efficacy parameter (d’ standard score) • Revised the definitions of the Safety and the ITT populations • Eliminated the category of efficacy assessments for simplification, since the information is contained in the SAP • Eliminated the stratification of inferential analyses by study center and/or geographic region • Revised exclusion criterion #8 to also exclude subjects with rare heredity disorders and exclusion criterion #9 to also exclude subjects with hypersensitivity to other excipients in study medication • Revised inclusion criterion #7 to allow the use of IQ scores available prior to Screening • Clarified the allowable interval between Screening and Baseline visits • Added a provision that the CPRS-R(S) may also be used as a safety assessment • Changed wording to clarify that glucose is to be assessed at other visits in addition to Screening Administrative changes included changes in the Eisai UK address and in contact information regarding reporting SAEs, pregnancies, deaths and life-threatening events.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Limitations of the study, such as early termination leading to small numbers of subjects analyzed and technical problems with measurement leading to unreliable or uninterpretable data.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Mon Apr 29 16:00:21 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA