Clinical Trial Results:
DoubleBlind, Randomized, PlaceboControlled, Crossover Study Evaluating the Academic, Behavioral and Cognitive Effects of CONCERTA® on Older Children with ADHD. The ABC Study.
Summary


EudraCT number 
201500104228 
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 

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information


Trial identification


Sponsor protocol code 
CONCERTAATT4080


Additional study identifiers


ISRCTN number 
  
US NCT number 
NCT00799487  
WHO universal trial number (UTN) 
  
Sponsors


Sponsor organisation name 
OrthoMcNeil Janssen Scientific Affairs LLC


Sponsor organisation address 
Archimedesweg 29, Leiden, Netherlands, 2333CM


Public contact 
Clinical Registry GroupJB BV, OrthoMcNeil Janssen Scientific Affairs LLC, ClinicalTrialsEU@its.jnj.com


Scientific contact 
Clinical Registry GroupJB BV, OrthoMcNeil 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 followup 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 (027 days) 
0


Infants and toddlers (28 days23 months) 
0


Children (211 years) 
79


Adolescents (1217 years) 
10


Adults (1864 years) 
0


From 65 to 84 years 
0


85 years and over 
0



Recruitment


Recruitment details 
  
Preassignment


Screening details 
A total of 89 participants were enrolled in the OpenLabel 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 
Nonrandomised  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 1854 (milligram per day) mg/day.




Period 2


Period 2 title 
DoubleBlind 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 1854 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 1854 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.





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.  



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 
Intentiontotreat  
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 
Intentiontotreat  
Subject analysis set description 
Participants randomized to receive Concerta at lab school day 1 or lab school day 2



End point title 
Hour 4 Permanent Product Math Test Attempted Score (PERMPAttempted)  
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 10minute 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 DoubleBlind Assessment Period Lab School Day




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
27.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
34.4  
upper limit 
20.2 


End point title 
Hour 4 Permanent Product Math Test Correct Score (PERMPCorrect)  
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 10minute 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
28


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
35.1  
upper limit 
20.8 


End point title 
Hour 4 Swanson, Kotkin, Alger, MFlynn and Pelham Scale for Deportment (SKAMPDeportment)  
End point description 
The SKAMP scale measures the manifestations of ADHD using an independent observer (teacher) rating of children impairment in classroom behavior. The SKAMPDeportment (SKAMPD) (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 7point 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.4  
upper limit 
6.6 


End point title 
Hour 4 Swanson, Kotkin, Alger, MFlynn and Pelham Scale for Attention (SKAMPAttention)  
End point description 
The SKAMP scale measures the manifestations of ADHD using an independent observer (teacher) rating of children impairment in classroom behavior. The SKAMPAttention (SKAMPA) (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 7point 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
4.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
3.2  
upper limit 
5.8 


End point title 
Hour 4 Swanson, Kotkin, Alger, MFlynn and Pelham Scale for Composite (SKAMPComposite)  
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 SKAMPD and SKAMPA 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
9.5


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.9  
upper limit 
12 


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 computerpresented square containing a square hole near the top (target) or bottom (nontarget) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a nontarget (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 DoubleBlind Assessment Period.




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
3.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
4.27  
upper limit 
2.74 


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 computerpresented square containing a square hole near the top (target) or bottom (nontarget) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a nontarget. 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
17.58


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
23.72  
upper limit 
11.45 


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 computerpresented square containing a square hole near the top (target) or bottom (nontarget) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a nontarget. 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
< 0.0001  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
30.33


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
39.29  
upper limit 
21.37 


End point title 
Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML2) Finger Windows Backwards  
End point description 
WRAML2 (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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.0297  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
1.13


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
2.15  
upper limit 
0.12 


End point title 
Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML2) Finger Windows Forwards  
End point description 
WRAML2 (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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.0955  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.84


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
1.84  
upper limit 
0.15 


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 computerpresented square containing a square hole near the top (target) or bottom (nontarget) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a nontarget. Responses to nontargets. 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.0002  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
14.37


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
21.52  
upper limit 
7.23 


End point title 
Hour 5.5 Wechsler Intelligence Scale for Children  3rd ed. (WISCIIIPI) 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.2335  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.26


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.7  
upper limit 
0.17 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.2321  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
2.51


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
6.67  
upper limit 
1.65 


End point title 
Hour 7.5 Test of Handwriting Skills (Revised) (THSR)  
End point description 
The THSR 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 lowercase letters of the alphabet in order, writing from dictation the upper and lowercase letters of the alphabet out of order, single digitnumbers 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.0015  
Method 
Mixed models analysis  
Parameter type 
LS Mean Differenc  
Point estimate 
3.52


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
5.64  
upper limit 
1.4 


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/gradeappropriate 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.0101  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
5.38


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
9.43  
upper limit 
1.33 


End point title 
Hour 5.5 Wechsler Intelligence Scale for Children  3rd ed. (WISCIIIPI) 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.6642  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.09


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.53  
upper limit 
0.34 


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 computerpresented square containing a square hole near the top (target) or bottom (nontarget) edge. The first half of the TOVA requires that the child sustain attention while the second half requires inhibition of response to a nontarget. 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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.004  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
35.3


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
58.89  
upper limit 
11.71 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.0012  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.08


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.14  
upper limit 
0.03 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.0051  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.07


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.12  
upper limit 
0.02 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.1768  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.05


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.13  
upper limit 
0.02 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Concerta v Placebo


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.4245  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.02


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.09  
upper limit 
0.04 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.9729  
Method 
Mixed models analysis  
Parameter type 
LS Mean DIfference  
Point estimate 
0


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.09  
upper limit 
0.09 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.3486  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.04


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.12  
upper limit 
0.04 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.1466  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.07  
upper limit 
0.01 


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 DoubleBlind Assessment Period




Statistical analysis title 
Placebo vs. Concerta  
Comparison groups 
Placebo v Concerta


Number of subjects included in analysis 
131


Analysis specification 
Posthoc


Analysis type 
noninferiority  
Pvalue 
= 0.1368  
Method 
Mixed models analysis  
Parameter type 
LS Mean Difference  
Point estimate 
0.03


Confidence interval 

level 
95%  
sides 
2sided


lower limit 
0.01  
upper limit 
0.08 


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 
Nonsystematic  
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  


Frequency threshold for reporting nonserious adverse events: 2%  



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 