CONCERTA Lab School Study

• Sponsor: Ortho-McNeil Janssen Scientific Affairs, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00799487
• Collaborator: (none)
• Enrollment: 89
• Locations: 3
• Arms: 2
• Actual Duration (Months): 5.7
• Patients Per Site: 29.7
• Patients Per Site Per Month: 5.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Attention Deficit Hyperactivity Disorder	Drug: CONCERTA (methylphenidate HCl) or placebo; Drug: CONCERTA (methylphenidate HCl) or placebo	Phase 4

Detailed Description

The hypothesis is that CONCERTA (methylphenidate HCl) is safe and effective in improving academic performance and behavior in children with ADHD when compared to placebo as demonstrated using specified study measures. This is a double-blind (neither participant nor investigator knows the name of the assigned study drug), randomized (study drug assigned by chance), placebo-controlled, crossover study evaluating the academic, behavioral and cognitive effects of CONCERTA (methylphenidate HCl) on older children with ADHD This means that all eligible children will receive treatment with methylphenidate HCl throughout the study (the titration and assessment periods) and inactive pill (placebo) on 1 of the 2 laboratory classroom days. On the other laboratory classroom day they will receive their regular dose of CONCERTA (methylphenidate HCl). The primary efficacy variable in this study is the Permanent Product Math Test (PERMP) attempted score. Secondary Measures include: SKAMP (Swanson, Kotkin, Agler, M-Flynn, and Pelham), tests of inattention, reading fluency and comprehension, and memory. Assessments will be completed during each of the laboratory assessment days (12.5 hours). Participants will be assessed for adverse events throughout the study. Patients will initiate treatment with oral CONCERTA (methylphenidate HCl) 18 mg at baseline and continue morning dosing with increases every 3 to 7 days until an optimal dose is achieved, up to the maximum of 54 mg/day. Eligible patients will remain in the study for a maximum of 8 weeks.

Study Design

• Study Type: Interventional
• Actual Enrollment: 89 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Double-Blind, Randomized, Placebo-Controlled, Crossover Study Evaluating the Academic, Behavioral and Cognitive Effects of CONCERTA on Older Children With ADHD (The ABC Study)
• Actual Study Start Date: Jan 2, 2009
• Actual Primary Completion Date: Jun 26, 2009
• Actual Study Completion Date: Jun 26, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 CONCERTA (methylphenidate HCl) or placebo Optimal Subject Dose (18mg-54mg) once daily during Lab School Day #1 with placebo on Day #2	Drug: CONCERTA (methylphenidate HCl) or placebo; Optimal Subject Dose (18mg-54mg) once daily during Lab School Day #1 with placebo on Day #2
Experimental: 2 CONCERTA (methylphenidate HCl) or placebo Optimal Subject Dose (18mg-54mg) once daily during Lab School Day #2 with placebo on Day #1	Drug: CONCERTA (methylphenidate HCl) or placebo; Optimal Subject Dose (18mg-54mg) once daily during Lab School Day #2 with placebo on Day #1

Outcome Measures

Primary Outcome Measures

1. Hour 4 Permanent Product Math Test Attempted Score (PERMP-Attempted) [Hour 4 of the Double-Blind Assessment Period Lab School Day]

   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.)

2. Hour 4 Permanent Product Math Test Correct Score (PERMP-Correct) [Hour 4 of the Lab School Day During the Double-Blind Assessment Period]

   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.

Secondary Outcome Measures

1. Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Deportment (SKAMP-Deportment) [Hour 4 of the Lab School Day During the Double-Blind Assessment Period]

   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.

2. Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Attention (SKAMP-Attention) [Hour 4 of the Lab School Day During the Double-Blind Assessment Period]

   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.

3. Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Composite (SKAMP-Composite) [Hour 4 of the Lab School Day During the Double-Blind Assessment Period]

   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.

4. Hour 5.5 Test of Variables of Attention (TOVA) ADHD Score [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

   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.

5. Hour 5.5 Test of Variables of Attention (TOVA) Reaction Time (Msec) [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

   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.

6. Hour 5.5 Test of Variables of Attention(TOVA) Reaction Time Variability (Standard Deviation in Milliseconds (Msecs)) [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

   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.

7. Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Backwards [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

   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.

8. Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Forwards [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

   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.

9. Hour 5.5 Test of Variables of Attention (TOVA) Commissions [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

   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).

10. Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Backwards [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

    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).

11. Hour 8.75 Gray Silent Reading Test (GSRT) [Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period]

    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.

12. Hour 7.5 Test of Handwriting Skills (Revised) (THS-R) [Hour 7.5 of the Lab School Day During the Double-Blind Assessment Period]

    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).

13. Hour 3.5 Dynamic Indicators of Basic Early Literacy Skills (DIBELS) [Hour 3.5 of the Lab School Day During the Double-Blind Assessment Period]

    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

14. Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Forwards [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

    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).

15. Hour 5.5 Test of Variables of Attention (TOVA) Omissions [Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period]

    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).

16. Hour 3.0 Grammar Task [Hour 3.0 of the Lab School Day During the Double-Blind Assessment Period]

    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).

17. Hour 8.75 Packet Activity - Short Story With Questions for Comprehension [Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period]

    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).

18. Hour 8.75 Packet Activity - Identiy Root Word [Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period]

    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).

19. Hour 8.75 Packet Activity - Alphabetize List of Words [Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period]

    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).

20. Hour 8.75 Packet Activity - Identify Multiple Meanings for Words [Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period]

    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).

21. Hour 8.75 Packet Activity - Complete Sentences Using Words Provided [Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period]

    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).

22. Hour 8.75 Packet Activity - Word Search [Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period]

    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).

23. Hour 8.75 Packet Activity - Decode the Mystery Sentence [Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period]

    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).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Years to 12 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• ADHD diagnosis of all subtypes (except Not Otherwise Specified)

• Patients with total or subscale Attention Deficit Hyperactivity Disorder Rating Scale (ADHD RS-IV) scores > =90th percentile relative to the general population of children by age and gender

• Patients currently receiving ADHD medication must be inadequately managed on their current stimulant dose and meet this criteria at the screening visit

• Ability to read and understand English

• Ability to attend school regularly

Exclusion Criteria:

• Estimated Full Scale IQ score of 80 or below, Severe Learning Disability

• History of or current, primary diagnosis of: severe anxiety disorder, conduct disorder, psychotic disorders, Pervasive Developmental Disorder, Eating Disorder, Obsessive-Compulsive Disorder, Sleep Disorder, Major Depressive Disorder, Bipolar Disorder, Substance Use Disorder, Chronic Tic Disorder, personal or family history of Tourette's Syndrome

• Weight < 3rd percentile for age

• History of hospitalization for treatment of a mood, anxiety, or psychotic disorder

• History of failed response to methylphenidate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Little Rock	Arkansas	United States
2		Las Vegas	Nevada	United States
3		Durham	North Carolina	United States

Sponsors and Collaborators

• Ortho-McNeil Janssen Scientific Affairs, LLC

Investigators

• Study Director: Ortho-McNeil Janssen Scientific Affairs, LLC Clinical Trial, Ortho-McNeil Janssen Scientific Affairs, LLC

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Double-Blind, Randomized, Placebo-Controlled, Crossover Study Evaluating the Academic, Behavioral and Cognitive Effects of CONCERTA on Older Children with ADHD

Publications

None provided.

• Responsible Party: Ortho-McNeil Janssen Scientific Affairs, LLC
• ClinicalTrials.gov Identifier: NCT00799487
• Other Study ID Numbers: CR015118; 2015-001042-28
• First Posted: Dec 1, 2008
• Last Update Posted: Mar 12, 2020
• Last Verified: Feb 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Keywords provided by Ortho-McNeil Janssen Scientific Affairs, LLC: ADHD; Attention Deficit Hyperactivity Disorder
• Additional relevant MeSH terms: Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Methylphenidate

Study Results

Participant Flow

Arm/Group Title	Not Randomized	Placebo/Concerta	Concerta/Placebo
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 and an individualized, optimal dose of Concerta (18mg, 36mg, or 54mg tablet) once daily at lab school day 2	Children randomized to receive an individualized, optimal dose of Concerta (18mg, 36mg, or 54mg tablet) once daily at lab school day 1 and Placebo at lab school day 2
Period Title: Dose Adjustment Period
STARTED	21	34	34
COMPLETED	0	34	34
NOT COMPLETED	21	0	0
Period Title: Dose Adjustment Period
STARTED	0	34	34
COMPLETED	0	33	32
NOT COMPLETED	0	1	2

Baseline Characteristics

Arm/Group Title	Not Randomized	Placebo/Concerta	Concerta/Placebo	Total
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 and Concerta lab school day 2	Children randomized to receive Concerta at lab school day 1 and Placebo at lab school day 2	Total of all reporting groups
Overall Participants	21	34	34	89
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.0 (1.00)	10.1 (1.07)	10.4 (0.99)	10.2 (1.03)
Sex: Female, Male (Count of Participants)
Female	6 28.6%	14 41.2%	9 26.5%	29 32.6%
Male	15 71.4%	20 58.8%	25 73.5%	60 67.4%
Region of Enrollment (participants) [Number]
USA	21 100%	34 100%	34 100%	89 100%

Outcome Measures

1. Primary Outcome

Title	Hour 4 Permanent Product Math Test Attempted Score (PERMP-Attempted)
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.)
Time Frame	Hour 4 of the Double-Blind Assessment Period Lab School Day

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Problems attempted]	88.0 (39.79)	116.1 (38.99)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were determined by using a repeated measures mixed model with actual value as the dependent variable with terms for treatment, time, treatment by time interaction, period, sequence, and baseline score.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-27.3
	Confidence Interval	(2-Sided) 95%; -34.4 to -20.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

2. Primary Outcome

Title	Hour 4 Permanent Product Math Test Correct Score (PERMP-Correct)
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.
Time Frame	Hour 4 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Problems correct]	84.0 (39.93)	112.8 (39.60)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were determined by using a repeated measures mixed model with actual value as the dependent variable with terms for treatment, time, treatment by time interaction, period, sequence, and baseline score.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-28.0
	Confidence Interval	(2-Sided) 95%; -35.1 to -20.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

3. Secondary Outcome

Title	Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Deportment (SKAMP-Deportment)
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.
Time Frame	Hour 4 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	8.0 (6.54)	3.1 (3.65)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were determined by using a repeated measures mixed model with actual value as the dependent variable with terms for treatment, time, treatment by time interaction, period, sequence, and baseline score.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	5.0
	Confidence Interval	(2-Sided) 95%; 3.4 to 6.6
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

4. Secondary Outcome

Title	Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Attention (SKAMP-Attention)
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.
Time Frame	Hour 4 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	10.1 (5.51)	5.6 (3.69)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were determined by using a repeated measures mixed model with actual value as the dependent variable with terms for treatment, time, treatment by time interaction, period, sequence, and baseline score.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	4.5
	Confidence Interval	(2-Sided) 95%; 3.2 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

5. Secondary Outcome

Title	Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Composite (SKAMP-Composite)
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.
Time Frame	Hour 4 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Chidren randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	18.1 (10.61)	8.7 (6.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were determined by using a repeated measures mixed model with actual value as the dependent variable with terms for treatment, time, treatment by time interaction, period, sequence, and baseline score.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	9.5
	Confidence Interval	(2-Sided) 95%; 6.9 to 12.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

6. Secondary Outcome

Title	Hour 5.5 Test of Variables of Attention (TOVA) ADHD Score
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.
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	-4.19 (3.563)	-0.68 (3.672)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.51
	Confidence Interval	(2-Sided) 95%; -4.27 to -2.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

7. Secondary Outcome

Title	Hour 5.5 Test of Variables of Attention (TOVA) Reaction Time (Msec)
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.
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Milliseconds (msecs)]	75.23 (26.740)	93.21 (32.619)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-17.58
	Confidence Interval	(2-Sided) 95%; -23.72 to -11.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

8. Secondary Outcome

Title	Hour 5.5 Test of Variables of Attention(TOVA) Reaction Time Variability (Standard Deviation in Milliseconds (Msecs))
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.
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or at lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [milliseconds]	56.58 (54.478)	87.22 (45.643)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-30.33
	Confidence Interval	(2-Sided) 95%; -39.29 to -21.37
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

9. Secondary Outcome

Title	Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Backwards
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.
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Correct Sequences]	9.8 (4.95)	10.9 (4.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0297
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-1.13
	Confidence Interval	(2-Sided) 95%; -2.15 to -0.12
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

10. Secondary Outcome

Title	Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Forwards
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.
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Correct Sequences]	12.3 (4.94)	13.2 (4.85)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0955
	Comments	P-values were determined by using a general linear mixed model. Finger Windows Forwards was the first non-significant p-value in the gatekeeper sequence.
	Method	Mixed Models Analysis
	Comments	Testing of additional endpoints in the sequence was still performed without any unqualified statements about the individual statistical significance.
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.84
	Confidence Interval	(2-Sided) 95%; -1.84 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

11. Secondary Outcome

Title	Hour 5.5 Test of Variables of Attention (TOVA) Commissions
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).
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Responses to non-targets]	78.35 (47.390)	90.54 (36.132)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0002
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-14.37
	Confidence Interval	(2-Sided) 95%; -21.52 to -7.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

12. Secondary Outcome

Title	Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Backwards
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).
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Correct Sequences]	4.8 (1.85)	5.1 (1.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2335
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 95%; -0.70 to 0.17
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

13. Secondary Outcome

Title	Hour 8.75 Gray Silent Reading Test (GSRT)
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.
Time Frame	Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	89.1 (19.44)	92.1 (19.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.2321
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-2.51
	Confidence Interval	(2-Sided) 95%; -6.67 to 1.65
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

14. Secondary Outcome

Title	Hour 7.5 Test of Handwriting Skills (Revised) (THS-R)
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).
Time Frame	Hour 7.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	79.1 (13.86)	82.7 (13.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0015
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-3.52
	Confidence Interval	(2-Sided) 95%; -5.64 to -1.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

15. Secondary Outcome

Title	Hour 3.5 Dynamic Indicators of Basic Early Literacy Skills (DIBELS)
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
Time Frame	Hour 3.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	110.8 (39.21)	117.8 (39.38)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0101
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-5.38
	Confidence Interval	(2-Sided) 95%; -9.43 to -1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

16. Secondary Outcome

Title	Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Forwards
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).
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Correct Sequences]	8.4 (1.60)	8.5 (1.56)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.6642
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 95%; -0.53 to 0.34
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

17. Secondary Outcome

Title	Hour 5.5 Test of Variables of Attention (TOVA) Omissions
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).
Time Frame	Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Targets missed]	36.34 (103.888)	71.49 (82.508)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0040
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-35.30
	Confidence Interval	(2-Sided) 95%; -58.89 to -11.71
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

18. Secondary Outcome

Title	Hour 3.0 Grammar Task
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).
Time Frame	Hour 3.0 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	0.252 (0.1894)	0.340 (0.2195)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0012
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.08
	Confidence Interval	(2-Sided) 95%; -0.14 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

19. Secondary Outcome

Title	Hour 8.75 Packet Activity - Short Story With Questions for Comprehension
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).
Time Frame	Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	0.619 (0.2435)	0.699 (0.2239)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.0051
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.12 to -0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

20. Secondary Outcome

Title	Hour 8.75 Packet Activity - Identiy Root Word
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).
Time Frame	Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	0.580 (0.3478)	0.638 (0.3230)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1768
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.13 to 0.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

21. Secondary Outcome

Title	Hour 8.75 Packet Activity - Alphabetize List of Words
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).
Time Frame	Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	0.638 (0.3269)	0.660 (0.3396)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.4245
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.02
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

22. Secondary Outcome

Title	Hour 8.75 Packet Activity - Identify Multiple Meanings for Words
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).
Time Frame	Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	0.814 (0.2936)	0.821 (0.2839)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.9729
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean DIfference
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 95%; -0.09 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

23. Secondary Outcome

Title	Hour 8.75 Packet Activity - Complete Sentences Using Words Provided
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).
Time Frame	Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	0.730 (0.3101)	0.781 (0.2926)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.3486
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.04
	Confidence Interval	(2-Sided) 95%; -0.12 to 0.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

24. Secondary Outcome

Title	Hour 8.75 Packet Activity - Word Search
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).
Time Frame	Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Children randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	0.955 (0.1272)	0.984 (0.0862)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1466
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95%; -0.07 to 0.01
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

25. Secondary Outcome

Title	Hour 8.75 Packet Activity - Decode the Mystery Sentence
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).
Time Frame	Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Outcome Measure Data

Analysis Population Description

No randomized children were included at this time point. The number of children treated with placebo is based on 68 children minus 3 children who did not crossover and minus 1 child who dropped out before laboratory day 2. The number of children treated with CONCERTA is based on 68 children minus 1 child who dropped out before laboratory day 2.

Arm/Group Title	Not Randomized	Placebo	Concerta
Arm/Group Description	Children who started dose adjustment period, but were not randomized	Children randomized to receive Placebo at lab school day 1 or lab school day 2	Chilfdren randomized to receive Concerta at lab school day 1 or lab school day 2
Measure Participants	0	64	67
Mean (Standard Deviation) [Units on a scale]	0.989 (0.0278)	0.955 (0.1661)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Concerta
	Comments
	Type of Statistical Test	Superiority or Other (legacy)
	Comments
Statistical Test of Hypothesis	p-Value	0.1368
	Comments	P-values were determined by using a general linear mixed model.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference
	Estimated Value	0.03
	Confidence Interval	(2-Sided) 95%; -0.01 to 0.08
	Parameter Dispersion	Type: Value:
	Estimation Comments	Placebo minus Concerta

Adverse Events

Time Frame	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).
Arm/Group Title	Placebo		Concerta		Open Label
Arm/Group Description	Placebo was received during the lab school day		Concerta was received during the lab school day		dose adjustment period and double blind period other than lab school day
All Cause Mortality
	Placebo		Concerta		Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Concerta		Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/67 (0%)		0/67 (0%)		0/89 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Concerta		Open Label
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/67 (7.5%)		9/67 (13.4%)		75/89 (84.3%)
Gastrointestinal disorders
Abdominal pain upper	2/67 (3%)		4/67 (6%)		25/89 (28.1%)
Vomiting	0/67 (0%)		0/67 (0%)		7/89 (7.9%)
Nausea	0/67 (0%)		0/67 (0%)		6/89 (6.7%)
General disorders
Irritability	0/67 (0%)		0/67 (0%)		11/89 (12.4%)
Fatigue	0/67 (0%)		0/67 (0%)		7/89 (7.9%)
Infections and infestations
Upper respiratory tract infection	1/67 (1.5%)		1/67 (1.5%)		9/89 (10.1%)
Pharyngitis	0/67 (0%)		0/67 (0%)		8/89 (9%)
Investigations
Weight decreased	0/67 (0%)		1/67 (1.5%)		6/89 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	0/67 (0%)		0/67 (0%)		20/89 (22.5%)
Anorexia	0/67 (0%)		0/67 (0%)		12/89 (13.5%)
Nervous system disorders
Headache	2/67 (3%)		4/67 (6%)		29/89 (32.6%)
Psychiatric disorders
Initial insomnia	0/67 (0%)		0/67 (0%)		26/89 (29.2%)
Affect lability	0/67 (0%)		0/67 (0%)		14/89 (15.7%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	0/67 (0%)		0/67 (0%)		9/89 (10.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.