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    Clinical Trial Results:
    Double-Blind, Randomized, Placebo-Controlled, Crossover Study Evaluating the Academic, Behavioral and Cognitive Effects of CONCERTA® on Older Children with ADHD. The ABC Study.

    Summary
    EudraCT number
    		 2015-001042-28
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    26 Jun 2009

    Results information
    Results version number
    		 v2(current)
    This version publication date
    10 Jul 2016
    First version publication date
    06 Aug 2015
    Other versions
    		 v1
    Version creation reason
    • Correction of full data set
    Review of data

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CONCERTA-ATT-4080
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00799487
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ortho-McNeil Janssen Scientific Affairs LLC
    Sponsor organisation address
    Archimedesweg 29, Leiden, Netherlands, 2333CM
    Public contact
    Clinical Registry Group-JB BV, Ortho-McNeil Janssen Scientific Affairs LLC, ClinicalTrialsEU@its.jnj.com
    Scientific contact
    Clinical Registry Group-JB BV, Ortho-McNeil Janssen Scientific Affairs LLC, ClinicalTrialsEU@its.jnj.com
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    26 Jun 2009
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    26 Jun 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this trial is to determine if the study medication, CONCERTA (methylphenidate HCl), is safe and effective in improving academic performance and behavior in children with Attention Deficit Hyperactivity Disorder (ADHD) when compared to placebo.
    Protection of trial subjects
    The safety assessments included the monitoring of adverse events (AEs), performing laboratory tests, measurement of vital signs, electrocardiogram (ECG) and performing physical examinations throughout the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    08 Dec 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
    United States: 89
    Worldwide total number of subjects
    89
    EEA total number of subjects
    0
    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)
    79
    Adolescents (12-17 years)
    10
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 A total of 89 participants were enrolled in the Open-Label Dose Adjustment Period and received at least 1 dose of study drug.

    Period 1
    Period 1 title
    Dose Adjustment Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Concerta
    Arm description
    		 Participants received Concerta in a dose of 18 milligram/day (mg/day) once daily orally. Concerta dose was increased as 18 mg/day every 3 to 7 days until an optimal individualized dose was achieved, up to a maximum dose of 54 mg/day.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Concerta
    Investigational medicinal product code
    Other name
    Methylphenidate hydrochloride
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Concerta capsule was administered in a dose of 18-54 (milligram per day) mg/day.

    Number of subjects in period 1
    		Concerta
    Started
    89
    Completed
    68
    Not completed
    21
         Consent withdrawn by subject
    3
         Adverse event, non-fatal
    2
         Not meet the optimal dose criteria
    8
         Withdrew for “other” reasons
    5
         Lost to follow-up
    1
         Withdrawn at the discretion of the investigator
    2
    Period 2
    Period 2 title
    Double-Blind Assessment Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    No

    Arm title
    		 Placebo/Concerta
    Arm description
    		 Children randomized to receive Placebo at lab school day 1 and Concerta lab school day 2
    Arm type
    		 Experimental

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matching with Concerta was administered.

    Investigational medicinal product name
    Concerta
    Investigational medicinal product code
    Other name
    Methylphenidate hydrochloride
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Concerta capsule was administered in a dose of 18-54 mg/day.

    Arm title
    		 Concerta/Placebo
    Arm description
    		 Children randomized to receive Concerta at lab school day 1 and Placebo at lab school day 2
    Arm type
    		 Experimental

    Investigational medicinal product name
    Concerta
    Investigational medicinal product code
    Other name
    Methylphenidate hydrochloride
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Concerta capsule was administered in a dose of 18-54 mg/day.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Capsule
    Routes of administration
    Oral use
    Dosage and administration details
    Placebo matching with Concerta was administered.

    Number of subjects in period 2
    		Placebo/Concerta Concerta/Placebo
    Started
    34
    34
    Completed
    33
    32
    Not completed
    1
    2
         Other
    1
    1
         Lost to follow-up
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Concerta
    Reporting group description
    		 Participants received Concerta in a dose of 18 milligram/day (mg/day) once daily orally. Concerta dose was increased as 18 mg/day every 3 to 7 days until an optimal individualized dose was achieved, up to a maximum dose of 54 mg/day.

    Reporting group values
    		 Concerta Total
    Number of subjects
    		 89 89
    Title for AgeCategorical
    Units: subjects
        Children (2-11 years)
    		 80 80
        Adolescents (12-17 years)
    		 9 9
        Adults (18-64 years)
    		 0 0
        From 65 to 84 years
    		 0 0
        85 years and over
    		 0 0
    Title for AgeContinuous
    Units: years
        arithmetic mean (standard deviation)
    		 10.2 ± 1.03 -
    Title for Gender
    Units: subjects
        Female
    		 29 29
        Male
    		 60 60

    End points

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    End points reporting groups
    Reporting group title
    Concerta
    Reporting group description
    		 Participants received Concerta in a dose of 18 milligram/day (mg/day) once daily orally. Concerta dose was increased as 18 mg/day every 3 to 7 days until an optimal individualized dose was achieved, up to a maximum dose of 54 mg/day.
    Reporting group title
    Placebo/Concerta
    Reporting group description
    		 Children randomized to receive Placebo at lab school day 1 and Concerta lab school day 2

    Reporting group title
    Concerta/Placebo
    Reporting group description
    		 Children randomized to receive Concerta at lab school day 1 and Placebo at lab school day 2

    Subject analysis set title
    Placebo
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants randomized to receive Placebo at lab school day 1 or lab school day 2

    Subject analysis set title
    Concerta
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    Participants randomized to receive Concerta at lab school day 1 or lab school day 2

    Primary: Hour 4 Permanent Product Math Test Attempted Score (PERMP-Attempted)

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    End point title
    		 Hour 4 Permanent Product Math Test Attempted Score (PERMP-Attempted)
    End point description
    PERMP (range: 0, 400) is a measure of academic productivity. These seatwork math tasks provide an objective measure of attention and accuracy in calculations. The level of difficulty is established on a screening math pretest. The subsequent laboratory school day assessments employed a series of 10-minute math tests (5 pages of 80 math problem each for a total of 400 problems available). Children were graded on the number of attempted problems. A higher number of problems attempted was indicative of greater attention to detail (higher score is preferable.)
    End point type
    Primary
    End point timeframe
    Hour 4 of the Double-Blind Assessment Period Lab School Day
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Problems attempted
        arithmetic mean (standard deviation)
    88 ± 39.79
    116.1 ± 38.99
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -27.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -34.4
         upper limit
    		 -20.2

    Primary: Hour 4 Permanent Product Math Test Correct Score (PERMP-Correct)

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    End point title
    		 Hour 4 Permanent Product Math Test Correct Score (PERMP-Correct)
    End point description
    PERMP (range: 0, 400) is a measure of academic productivity. These seatwork math tasks provide an objective measure of attention and accuracy in calculations. The level of difficulty is established on a screening math pretest. The subsequent laboratory school day assessments employed a series of 10-minute math tests (5 pages of 80 math problem each for a total of 400 problems available). Children were graded on the number of correct problems. A higher number of problems correct, of those attempted, was indicative of greater accuracy.
    End point type
    Primary
    End point timeframe
    Hour 4 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Problems correct
        arithmetic mean (standard deviation)
    84 ± 39.93
    112.8 ± 39.6
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.1
         upper limit
    		 -20.8

    Secondary: Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Deportment (SKAMP-Deportment)

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    End point title
    		 Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Deportment (SKAMP-Deportment)
    End point description
    The SKAMP scale measures the manifestations of ADHD using an independent observer (teacher) rating of children impairment in classroom behavior. The SKAMP-Deportment (SKAMP-D) (range: 0,36) is a sum of ratings on 6 deportment items (interacting with other children, interacting with adults, remaining quiet, staying seated, complying with the teacher’s directions, and following the classroom rules). Each item was rated on a 7-point impairment scale (0=normal, 6=maximum impairment), with higher scores indicating more severe symptoms.
    End point type
    Secondary
    End point timeframe
    Hour 4 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    8 ± 6.54
    3.1 ± 3.65
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.4
         upper limit
    		 6.6

    Secondary: Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Attention (SKAMP-Attention)

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    End point title
    		 Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Attention (SKAMP-Attention)
    End point description
    The SKAMP scale measures the manifestations of ADHD using an independent observer (teacher) rating of children impairment in classroom behavior. The SKAMP-Attention (SKAMP-A) (range: 0, 42) is a sum of the ratings on 7 attention items (getting started, sticking with tasks, attending to an activity, making activity transitions, completing assigned tasks, performing work accurately, and being neat and careful while writing or drawing). Each item was rated on a 7-point impairment scale (0=normal, 6=maximum impairment), with higher scores indicating more severe symptoms.
    End point type
    Secondary
    End point timeframe
    Hour 4 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    10.1 ± 5.51
    5.6 ± 3.69
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    4.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.2
         upper limit
    		 5.8

    Secondary: Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Composite (SKAMP-Composite)

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    End point title
    		 Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Composite (SKAMP-Composite)
    End point description
    The SKAMP scale measures the manifestations of ADHD using an independent observer (teacher) rating of child impairment in classroom behavior. A composite score (range: 0, 78) for the SKAMP variable (13 items total) was obtained by summing the SKAMP-D and SKAMP-A subscale scores. A lower score was preferable, as a higher score represented greater behavioral impairment.
    End point type
    Secondary
    End point timeframe
    Hour 4 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    18.1 ± 10.61
    8.7 ± 6.1
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    9.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.9
         upper limit
    		 12

    Secondary: Hour 5.5 Test of Variables of Attention (TOVA) ADHD Score

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    End point title
    		 Hour 5.5 Test of Variables of Attention (TOVA) ADHD Score
    End point description
    The TOVA is a computerized, visual continuous performance test which provides measures of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a non-target (observed range: -15.2, 5.2). An ADHD score of less than -1.80 is suggestive of ADHD.
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period.
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    -4.19 ± 3.563
    -0.68 ± 3.672
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -3.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.27
         upper limit
    		 -2.74

    Secondary: Hour 5.5 Test of Variables of Attention (TOVA) Reaction Time (Msec)

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    End point title
    		 Hour 5.5 Test of Variables of Attention (TOVA) Reaction Time (Msec)
    End point description
    The TOVA is a computerized, visual continuous performance test which provides measures of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a non-target. Mean response latency in msecs (observed range: -75.4, 129.5). Higher score indicates faster reaction time.
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Milliseconds (msecs)
        arithmetic mean (standard deviation)
    75.23 ± 26.74
    93.21 ± 32.619
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -17.58
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.72
         upper limit
    		 -11.45

    Secondary: Hour 5.5 Test of Variables of Attention(TOVA) Reaction Time Variability (Standard Deviation in Milliseconds (Msecs))

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    End point title
    		 Hour 5.5 Test of Variables of Attention(TOVA) Reaction Time Variability (Standard Deviation in Milliseconds (Msecs))
    End point description
    The TOVA is a computerized, visual continuous performance test which provides measures of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a non-target. SD of response times (msecs) (observed range: -177.6, 132.9). Higher score indicates less variability.
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: milliseconds
        arithmetic mean (standard deviation)
    56.58 ± 54.478
    87.22 ± 45.643
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 < 0.0001
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -30.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -39.29
         upper limit
    		 -21.37

    Secondary: Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Backwards

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    End point title
    		 Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Backwards
    End point description
    WRAML-2 (range: 0, 28) is designed to evaluate a child’s ability to learn and to memorize information, consists of 9 subtests from which 4 summary indexes can be calculated: verbal memory index, visual memory index, learning index, and general memory index. During this test the investigator pointed to a longer and longer series of windows on a card at the rate of 1 location per second, and then the child was asked to reproduce the sequence exactly in reverse order. One point was given for each correctly recalled sequence, and the test was discontinued after 3 consecutive errors.
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Correct Sequences
        arithmetic mean (standard deviation)
    9.8 ± 4.95
    10.9 ± 4.5
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0297
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -1.13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.15
         upper limit
    		 -0.12

    Secondary: Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Forwards

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    End point title
    		 Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Forwards
    End point description
    WRAML-2 (range: 0, 28) is designed to evaluate a child’s ability to learn and to memorize information, consists of 9 subtests from which 4 summary indexes can be calculated: verbal memory index, visual memory index, learning index, and general memory index. During this test the investigator pointed to a longer and longer series of windows on a card at the rate of 1 location per second, and then the child was asked to reproduce the sequence exactly. One point was given for each correctly recalled sequence, and the test was discontinued after 3 consecutive errors.
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Correct Sequences
        arithmetic mean (standard deviation)
    12.3 ± 4.94
    13.2 ± 4.85
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0955
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.84
         upper limit
    		 0.15

    Secondary: Hour 5.5 Test of Variables of Attention (TOVA) Commissions

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    End point title
    		 Hour 5.5 Test of Variables of Attention (TOVA) Commissions
    End point description
    The TOVA is a computerized, visual continuous performance test which provides measures of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a non-target. Responses to non-targets. Higher score is preferable (observed range: -82.4, 128.9).
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Responses to non-targets
        arithmetic mean (standard deviation)
    78.35 ± 47.39
    90.54 ± 36.132
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0002
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -14.37
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.52
         upper limit
    		 -7.23

    Secondary: Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Backwards

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    End point title
    		 Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Backwards
    End point description
    Each child individually was given a sequence of numbers with the sequence becoming progressively longer. The child was then asked to repeat the digits in the same sequence, either forwards or backwards. Each sequence length was attempted twice. The test was complete after failure on both trials of any sequence length. One point was awarded if the participant passed only 1 trial of a sequence length. Zero points were given if the participant failed both trials. The maximum raw scores were 16 forwards and 14 backwards. A higher score was indicative of better recall and attention (range: 0, 14).
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Correct Sequences
        arithmetic mean (standard deviation)
    4.8 ± 1.85
    5.1 ± 1.87
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.2335
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.7
         upper limit
    		 0.17

    Secondary: Hour 8.75 Gray Silent Reading Test (GSRT)

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    End point title
    		 Hour 8.75 Gray Silent Reading Test (GSRT)
    End point description
    Gray Silent Reading Test (GSRT) is a reliable, validated measure of reading comprehension administered in the group setting during the first half hour of the homework session (observed range: 0, 141). A higher score is preferable as it means more questions were answered correctly.
    End point type
    Secondary
    End point timeframe
    Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    89.1 ± 19.44
    92.1 ± 19.03
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.2321
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -2.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.67
         upper limit
    		 1.65

    Secondary: Hour 7.5 Test of Handwriting Skills (Revised) (THS-R)

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    End point title
    		 Hour 7.5 Test of Handwriting Skills (Revised) (THS-R)
    End point description
    The THS-R is a standardized, untimed assessment designed to evaluate neurosensory integration manifested in manuscript and cursive writing. The test includes the 10 subtests: writing from memory the upper- and lower-case letters of the alphabet in order, writing from dictation the upper and lower-case letters of the alphabet out of order, single digit-numbers out of order, selected words, and copying selected letters, words, and sentences. Each subtest was scored from zero (poorly formed letters) to 3 (perfectly formed letters). A higher score was preferable (observed range: 0, 118).
    End point type
    Secondary
    End point timeframe
    Hour 7.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    79.1 ± 13.86
    82.7 ± 13.34
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0015
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Differenc
    Point estimate
    -3.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -5.64
         upper limit
    		 -1.4

    Secondary: Hour 3.5 Dynamic Indicators of Basic Early Literacy Skills (DIBELS)

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    End point title
    		 Hour 3.5 Dynamic Indicators of Basic Early Literacy Skills (DIBELS)
    End point description
    The DIBELS (observed range: 0, 212), used to assess reading fluency, consists of standardized, individually administered measures of early literacy development. These short (1 minute) fluency measures were developed based upon essential early literacy domains to assess development of phonological awareness, alphabetic understanding, and automaticity and fluency. Only the paragraph fluency component of an age/grade-appropriate DIBELS was used. Children read 3 stories and completed the forms. A higher score was preferable and indicated a greater number of words read correctly in the time allowed.
    End point type
    Secondary
    End point timeframe
    Hour 3.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    110.8 ± 39.21
    117.8 ± 39.38
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0101
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -5.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -9.43
         upper limit
    		 -1.33

    Secondary: Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Forwards

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    End point title
    		 Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Forwards
    End point description
    Each child individually was given a sequence of numbers with the sequence becoming progressively longer. The child was then asked to repeat the digits in the same sequence, either forwards or backwards. Each sequence length was attempted twice. The test was complete after failure on both trials of any sequence length. One point was awarded if the participant passed only 1 trial of a sequence length. Zero points were given if the participant failed both trials. The maximum raw scores were 16 forwards and 14 backwards. A higher score was indicative of better recall and attention (range: 0, 16).
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Correct Sequences
        arithmetic mean (standard deviation)
    8.4 ± 1.6
    8.5 ± 1.56
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.6642
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.09
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.53
         upper limit
    		 0.34

    Secondary: Hour 5.5 Test of Variables of Attention (TOVA) Omissions

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    End point title
    		 Hour 5.5 Test of Variables of Attention (TOVA) Omissions
    End point description
    The TOVA is a computerized, visual continuous performance test which provides measures of attention. The stimulus, presented for 100 milliseconds (ms) at the rate of 30 per minute, is a computer-presented square containing a square hole near the top (target) or bottom (non-target) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a non-target. Number of targets missed. Higher score is preferable (observed range: -419.4, 108.9).
    End point type
    Secondary
    End point timeframe
    Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Targets missed
        arithmetic mean (standard deviation)
    36.34 ± 103.888
    71.49 ± 82.508
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.004
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -35.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -58.89
         upper limit
    		 -11.71

    Secondary: Hour 3.0 Grammar Task

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    End point title
    		 Hour 3.0 Grammar Task
    End point description
    This task, presented once during a laboratory school day, was designed to index “attention to detail” by determining how many grammatical mistakes each child could identify and circle in a brief paragraph. The errors were not difficult to identify and were designed to show attention to task, not comprehension. A higher number of errors identified, of those possible, was indicative of better attention - identification of grammatical errors (range: 0, 1 represents correct responses divided by the number of possible responses).
    End point type
    Secondary
    End point timeframe
    Hour 3.0 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.252 ± 0.1894
    0.34 ± 0.2195
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0012
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.14
         upper limit
    		 -0.03

    Secondary: Hour 8.75 Packet Activity - Short Story With Questions for Comprehension

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    End point title
    		 Hour 8.75 Packet Activity - Short Story With Questions for Comprehension
    End point description
    Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order)(range: 0, 1 represents correct responses divided by the number of possible responses).
    End point type
    Secondary
    End point timeframe
    Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.619 ± 0.2435
    0.699 ± 0.2239
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.0051
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 -0.02

    Secondary: Hour 8.75 Packet Activity - Identiy Root Word

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    End point title
    		 Hour 8.75 Packet Activity - Identiy Root Word
    End point description
    Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses).
    End point type
    Secondary
    End point timeframe
    Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.58 ± 0.3478
    0.638 ± 0.323
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.1768
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.05
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.13
         upper limit
    		 0.02

    Secondary: Hour 8.75 Packet Activity - Alphabetize List of Words

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    End point title
    		 Hour 8.75 Packet Activity - Alphabetize List of Words
    End point description
    Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses).
    End point type
    Secondary
    End point timeframe
    Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.638 ± 0.3269
    0.66 ± 0.3396
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Concerta v Placebo
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.4245
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.04

    Secondary: Hour 8.75 Packet Activity - Identify Multiple Meanings for Words

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    End point title
    		 Hour 8.75 Packet Activity - Identify Multiple Meanings for Words
    End point description
    Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses).
    End point type
    Secondary
    End point timeframe
    Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.814 ± 0.2936
    0.821 ± 0.2839
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.9729
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean DIfference
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.09
         upper limit
    		 0.09

    Secondary: Hour 8.75 Packet Activity - Complete Sentences Using Words Provided

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    End point title
    		 Hour 8.75 Packet Activity - Complete Sentences Using Words Provided
    End point description
    Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses).
    End point type
    Secondary
    End point timeframe
    Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.73 ± 0.3101
    0.781 ± 0.2926
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.3486
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 0.04

    Secondary: Hour 8.75 Packet Activity - Word Search

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    End point title
    		 Hour 8.75 Packet Activity - Word Search
    End point description
    Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses).
    End point type
    Secondary
    End point timeframe
    Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.955 ± 0.1272
    0.984 ± 0.0862
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.1466
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    -0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.07
         upper limit
    		 0.01

    Secondary: Hour 8.75 Packet Activity - Decode the Mystery Sentence

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    End point title
    		 Hour 8.75 Packet Activity - Decode the Mystery Sentence
    End point description
    Packet Activities: Assessment of ability to organize, listen to instructions, initiate task, complete task, and distractibility, by completing a word search, reading a short story for comprehension on a multiple choice test, reading a longer story for comprehension on a true/false test, decoding a mystery sentence, and completing various vocabulary assessments (word choice, homophones; base/root words, alphabetic order) (range: 0, 1 represents correct responses divided by the number of possible responses).
    End point type
    Secondary
    End point timeframe
    Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period
    End point values
    		 Placebo Concerta
    Number of subjects analysed
    64
    67
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.989 ± 0.0278
    0.955 ± 0.1661
    Statistical analysis title
    		 Placebo vs. Concerta
    Comparison groups
    Placebo v Concerta
    Number of subjects included in analysis
    131
    Analysis specification
    Post-hoc
    Analysis type
    		 non-inferiority
    P-value
    		 = 0.1368
    Method
    		 Mixed models analysis
    Parameter type
    		 LS Mean Difference
    Point estimate
    0.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.01
         upper limit
    		 0.08

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    The sponsor collects adverse events for 14 weeks starting with the signing of the informed consent (up to 4 weeks prior to treatment) continuing until the final visit at early discontinuation or study completion (up to 10 weeks after start of treatment).
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    11.1
    Reporting groups
    Reporting group title
    CONCERTA
    Reporting group description
    		 Concerta was received during the lab school day

    Reporting group title
    CONCERTA/PLACEBO
    Reporting group description
    		 Children randomized to receive Concerta at lab school day 1 and Placebo at lab school day 2

    Reporting group title
    PLACEBO/CONCERTA
    Reporting group description
    		 Children randomized to receive Placebo at lab school day 1 and Concerta lab school day 2

    Serious adverse events
    		 CONCERTA CONCERTA/PLACEBO PLACEBO/CONCERTA
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    0 / 34 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    Frequency threshold for reporting non-serious adverse events: 2%
    Non-serious adverse events
    		 CONCERTA CONCERTA/PLACEBO PLACEBO/CONCERTA
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 21 (0.00%)
    32 / 34 (94.12%)
    31 / 34 (91.18%)
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    0 / 21 (0.00%)
    3 / 34 (8.82%)
    2 / 34 (5.88%)
         occurrences all number
    0
    3
    2
    Irritability
         subjects affected / exposed
    0 / 21 (0.00%)
    5 / 34 (14.71%)
    3 / 34 (8.82%)
         occurrences all number
    0
    5
    4
    Pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Thirst
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 34 (5.88%)
    1 / 34 (2.94%)
         occurrences all number
    0
    3
    1
    Epistaxis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Dyspnoea
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Nasal Congestion
         subjects affected / exposed
    0 / 21 (0.00%)
    4 / 34 (11.76%)
    3 / 34 (8.82%)
         occurrences all number
    0
    5
    3
    Oropharyngeal Pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Rhinorrhoea
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Psychiatric disorders
    Abnormal Behaviour
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 34 (5.88%)
    1 / 34 (2.94%)
         occurrences all number
    0
    2
    1
    Aggression
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Affect Lability
         subjects affected / exposed
    0 / 21 (0.00%)
    5 / 34 (14.71%)
    6 / 34 (17.65%)
         occurrences all number
    0
    5
    6
    Anxiety
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Emotional Disorder
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 34 (5.88%)
    0 / 34 (0.00%)
         occurrences all number
    0
    4
    0
    Impulsive Behaviour
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    3
    0
    Initial Insomnia
         subjects affected / exposed
    0 / 21 (0.00%)
    11 / 34 (32.35%)
    9 / 34 (26.47%)
         occurrences all number
    0
    12
    9
    Insomnia
         subjects affected / exposed
    0 / 21 (0.00%)
    3 / 34 (8.82%)
    0 / 34 (0.00%)
         occurrences all number
    0
    4
    0
    Mood Swings
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    3
    Onychophagia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Social Avoidant Behaviour
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Tic
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Investigations
    Blood Pressure Increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Heart Rate Increased
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    2
    Weight Decreased
         subjects affected / exposed
    0 / 21 (0.00%)
    4 / 34 (11.76%)
    3 / 34 (8.82%)
         occurrences all number
    0
    4
    3
    Injury, poisoning and procedural complications
    Excoriation
         subjects affected / exposed
    0 / 21 (0.00%)
    3 / 34 (8.82%)
    1 / 34 (2.94%)
         occurrences all number
    0
    3
    1
    Facial Bones Fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Fracture
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Joint Sprain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    2
    Limb Injury
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle Strain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    1
    Skin Laceration
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 34 (5.88%)
    0 / 34 (0.00%)
         occurrences all number
    0
    2
    0
    Dizziness Postural
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Headache
         subjects affected / exposed
    0 / 21 (0.00%)
    12 / 34 (35.29%)
    14 / 34 (41.18%)
         occurrences all number
    0
    16
    26
    Lethargy
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Psychomotor Hyperactivity
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 34 (5.88%)
    0 / 34 (0.00%)
         occurrences all number
    0
    4
    0
    Ear and labyrinth disorders
    Ear Pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    2 / 34 (5.88%)
         occurrences all number
    0
    1
    2
    Eye disorders
    Conjunctivitis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal disorders
    Abdominal Pain Upper
         subjects affected / exposed
    0 / 21 (0.00%)
    13 / 34 (38.24%)
    9 / 34 (26.47%)
         occurrences all number
    0
    15
    11
    Diarrhoea
         subjects affected / exposed
    0 / 21 (0.00%)
    3 / 34 (8.82%)
    3 / 34 (8.82%)
         occurrences all number
    0
    4
    4
    Constipation
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Gastritis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Dry Mouth
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    0
    0
    2
    Nausea
         subjects affected / exposed
    0 / 21 (0.00%)
    3 / 34 (8.82%)
    1 / 34 (2.94%)
         occurrences all number
    0
    5
    1
    Toothache
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    3 / 34 (8.82%)
         occurrences all number
    0
    1
    3
    Vomiting
         subjects affected / exposed
    0 / 21 (0.00%)
    4 / 34 (11.76%)
    2 / 34 (5.88%)
         occurrences all number
    0
    6
    3
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Renal and urinary disorders
    Pollakiuria
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    1 / 34 (2.94%)
         occurrences all number
    0
    1
    1
    Back Pain
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Muscle Spasms
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Myalgia
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Neck Pain
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Pain in Extremity
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Gastroenteritis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 34 (5.88%)
    0 / 34 (0.00%)
         occurrences all number
    0
    2
    0
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 21 (0.00%)
    2 / 34 (5.88%)
    6 / 34 (17.65%)
         occurrences all number
    0
    2
    6
    Pharyngitis Streptococcal
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 21 (0.00%)
    1 / 34 (2.94%)
    0 / 34 (0.00%)
         occurrences all number
    0
    1
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 21 (0.00%)
    5 / 34 (14.71%)
    6 / 34 (17.65%)
         occurrences all number
    0
    5
    6
    Viral Infection
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Viral Pharyngitis
         subjects affected / exposed
    0 / 21 (0.00%)
    0 / 34 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    0
    0
    1
    Metabolism and nutrition disorders
    Anorexia
         subjects affected / exposed
    0 / 21 (0.00%)
    4 / 34 (11.76%)
    4 / 34 (11.76%)
         occurrences all number
    0
    4
    6
    Decreased Appetite
         subjects affected / exposed
    0 / 21 (0.00%)
    8 / 34 (23.53%)
    7 / 34 (20.59%)
         occurrences all number
    0
    8
    7

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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.
    None reported
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    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.

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