Trial Outcomes & Findings for CONCERTA Lab School Study (NCT NCT00799487)

NCT ID: NCT00799487

Last Updated: 2020-03-12

Results Overview

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.)

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 89 participants
• Primary outcome timeframe: Hour 4 of the Double-Blind Assessment Period Lab School Day
• Results posted on: 2020-03-12

Participant Flow

Participant milestones

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo/Concerta 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	Concerta/Placebo 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
Dose Adjustment Period STARTED	21	34	34
Dose Adjustment Period COMPLETED	0	34	34
Dose Adjustment Period NOT COMPLETED	21	0	0
Double-Blind Assessment Period STARTED	0	34	34
Double-Blind Assessment Period COMPLETED	0	33	32
Double-Blind Assessment Period NOT COMPLETED	0	1	2

Reasons for withdrawal

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo/Concerta 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	Concerta/Placebo 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
Dose Adjustment Period Lost to Follow-up	1	0	0
Dose Adjustment Period Adverse Event	2	0	0
Dose Adjustment Period Optimal Dose Not Achieved	8	0	0
Dose Adjustment Period Investigator Discretion	2	0	0
Dose Adjustment Period Withdrawal by Subject	3	0	0
Dose Adjustment Period Parent to home school child (exclusion)	1	0	0
Dose Adjustment Period Child too young (exclusion)	1	0	0
Dose Adjustment Period Missed laboratory day 1	1	0	0
Dose Adjustment Period ADHD RS-IV rating scale >85th percentile	2	0	0
Double-Blind Assessment Period Lost to Follow-up	0	0	1
Double-Blind Assessment Period Subject was out of the state	0	0	1
Double-Blind Assessment Period Overslept and missed lab day 2	0	1	0

Baseline Characteristics

CONCERTA Lab School Study

Baseline characteristics by cohort

Measure	Not Randomized n=21 Participants Children who started dose adjustment period, but were not randomized	Placebo/Concerta n=34 Participants Children randomized to receive Placebo at lab school day 1 and Concerta lab school day 2	Concerta/Placebo n=34 Participants Children randomized to receive Concerta at lab school day 1 and Placebo at lab school day 2	Total n=89 Participants Total of all reporting groups
Age, Continuous	10.0 years STANDARD_DEVIATION 1.00 • n=5 Participants	10.1 years STANDARD_DEVIATION 1.07 • n=7 Participants	10.4 years STANDARD_DEVIATION 0.99 • n=5 Participants	10.2 years STANDARD_DEVIATION 1.03 • n=4 Participants
Sex: Female, Male Female	6 Participants n=5 Participants	14 Participants n=7 Participants	9 Participants n=5 Participants	29 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	20 Participants n=7 Participants	25 Participants n=5 Participants	60 Participants n=4 Participants
Region of Enrollment USA	21 participants n=5 Participants	34 participants n=7 Participants	34 participants n=5 Participants	89 participants n=4 Participants

PRIMARY outcome

Timeframe: Hour 4 of the Double-Blind Assessment Period Lab School Day

Population: 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.

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.)

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 4 Permanent Product Math Test Attempted Score (PERMP-Attempted)	—	88.0 Problems attempted Standard Deviation 39.79	116.1 Problems attempted Standard Deviation 38.99

PRIMARY outcome

Timeframe: Hour 4 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 4 Permanent Product Math Test Correct Score (PERMP-Correct)	—	84.0 Problems correct Standard Deviation 39.93	112.8 Problems correct Standard Deviation 39.60

SECONDARY outcome

Timeframe: Hour 4 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Deportment (SKAMP-Deportment)	—	8.0 Units on a scale Standard Deviation 6.54	3.1 Units on a scale Standard Deviation 3.65

SECONDARY outcome

Timeframe: Hour 4 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Attention (SKAMP-Attention)	—	10.1 Units on a scale Standard Deviation 5.51	5.6 Units on a scale Standard Deviation 3.69

SECONDARY outcome

Timeframe: Hour 4 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 4 Swanson, Kotkin, Alger, M-Flynn and Pelham Scale for Composite (SKAMP-Composite)	—	18.1 Units on a scale Standard Deviation 10.61	8.7 Units on a scale Standard Deviation 6.10

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Test of Variables of Attention (TOVA) ADHD Score	—	-4.19 Units on a scale Standard Deviation 3.563	-0.68 Units on a scale Standard Deviation 3.672

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Test of Variables of Attention (TOVA) Reaction Time (Msec)	—	75.23 Milliseconds (msecs) Standard Deviation 26.740	93.21 Milliseconds (msecs) Standard Deviation 32.619

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Test of Variables of Attention(TOVA) Reaction Time Variability (Standard Deviation in Milliseconds (Msecs))	—	56.58 milliseconds Standard Deviation 54.478	87.22 milliseconds Standard Deviation 45.643

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Backwards	—	9.8 Correct Sequences Standard Deviation 4.95	10.9 Correct Sequences Standard Deviation 4.5

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Wide Range Assessment of Memory and Learning (WRAML-2) Finger Windows Forwards	—	12.3 Correct Sequences Standard Deviation 4.94	13.2 Correct Sequences Standard Deviation 4.85

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Test of Variables of Attention (TOVA) Commissions	—	78.35 Responses to non-targets Standard Deviation 47.390	90.54 Responses to non-targets Standard Deviation 36.132

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Backwards	—	4.8 Correct Sequences Standard Deviation 1.85	5.1 Correct Sequences Standard Deviation 1.87

SECONDARY outcome

Timeframe: Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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.

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 8.75 Gray Silent Reading Test (GSRT)	—	89.1 Units on a scale Standard Deviation 19.44	92.1 Units on a scale Standard Deviation 19.03

SECONDARY outcome

Timeframe: Hour 7.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 7.5 Test of Handwriting Skills (Revised) (THS-R)	—	79.1 Units on a scale Standard Deviation 13.86	82.7 Units on a scale Standard Deviation 13.34

SECONDARY outcome

Timeframe: Hour 3.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 3.5 Dynamic Indicators of Basic Early Literacy Skills (DIBELS)	—	110.8 Units on a scale Standard Deviation 39.21	117.8 Units on a scale Standard Deviation 39.38

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Wechsler Intelligence Scale for Children - 3rd ed. (WISC-III-PI) Digit Span Forwards	—	8.4 Correct Sequences Standard Deviation 1.60	8.5 Correct Sequences Standard Deviation 1.56

SECONDARY outcome

Timeframe: Hour 5.5 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 5.5 Test of Variables of Attention (TOVA) Omissions	—	36.34 Targets missed Standard Deviation 103.888	71.49 Targets missed Standard Deviation 82.508

SECONDARY outcome

Timeframe: Hour 3.0 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 3.0 Grammar Task	—	0.252 Units on a scale Standard Deviation 0.1894	0.340 Units on a scale Standard Deviation 0.2195

SECONDARY outcome

Timeframe: Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 8.75 Packet Activity - Short Story With Questions for Comprehension	—	0.619 Units on a scale Standard Deviation 0.2435	0.699 Units on a scale Standard Deviation 0.2239

SECONDARY outcome

Timeframe: Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 8.75 Packet Activity - Identiy Root Word	—	0.580 Units on a scale Standard Deviation 0.3478	0.638 Units on a scale Standard Deviation 0.3230

SECONDARY outcome

Timeframe: Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 8.75 Packet Activity - Alphabetize List of Words	—	0.638 Units on a scale Standard Deviation 0.3269	0.660 Units on a scale Standard Deviation 0.3396

SECONDARY outcome

Timeframe: Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 8.75 Packet Activity - Identify Multiple Meanings for Words	—	0.814 Units on a scale Standard Deviation 0.2936	0.821 Units on a scale Standard Deviation 0.2839

SECONDARY outcome

Timeframe: Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 8.75 Packet Activity - Complete Sentences Using Words Provided	—	0.730 Units on a scale Standard Deviation 0.3101	0.781 Units on a scale Standard Deviation 0.2926

SECONDARY outcome

Timeframe: Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 8.75 Packet Activity - Word Search	—	0.955 Units on a scale Standard Deviation 0.1272	0.984 Units on a scale Standard Deviation 0.0862

SECONDARY outcome

Timeframe: Hour 8.75 of the Lab School Day During the Double-Blind Assessment Period

Population: 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.

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).

Outcome measures

Measure	Not Randomized Children who started dose adjustment period, but were not randomized	Placebo n=64 Participants Children randomized to receive Placebo at lab school day 1 or lab school day 2	Concerta n=67 Participants Children randomized to receive Concerta at lab school day 1 or lab school day 2
Hour 8.75 Packet Activity - Decode the Mystery Sentence	—	0.989 Units on a scale Standard Deviation 0.0278	0.955 Units on a scale Standard Deviation 0.1661

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Concerta

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Open Label

Serious events: 0 serious events

Other events: 75 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=67 participants at risk Placebo was received during the lab school day	Concerta n=67 participants at risk Concerta was received during the lab school day	Open Label n=89 participants at risk dose adjustment period and double blind period other than lab school day
Gastrointestinal disorders Nausea	0.00% 0/67 • 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).	0.00% 0/67 • 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).	6.7% 6/89 • 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).
Metabolism and nutrition disorders Decreased appetite	0.00% 0/67 • 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).	0.00% 0/67 • 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).	22.5% 20/89 • 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).
Metabolism and nutrition disorders Anorexia	0.00% 0/67 • 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).	0.00% 0/67 • 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).	13.5% 12/89 • 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).
Nervous system disorders Headache	3.0% 2/67 • 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).	6.0% 4/67 • 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).	32.6% 29/89 • 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).
General disorders Irritability	0.00% 0/67 • 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).	0.00% 0/67 • 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).	12.4% 11/89 • 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).
Psychiatric disorders Initial insomnia	0.00% 0/67 • 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).	0.00% 0/67 • 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).	29.2% 26/89 • 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).
Psychiatric disorders Affect lability	0.00% 0/67 • 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).	0.00% 0/67 • 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).	15.7% 14/89 • 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).
Gastrointestinal disorders Abdominal pain upper	3.0% 2/67 • 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).	6.0% 4/67 • 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).	28.1% 25/89 • 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).
Gastrointestinal disorders Vomiting	0.00% 0/67 • 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).	0.00% 0/67 • 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).	7.9% 7/89 • 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).
General disorders Fatigue	0.00% 0/67 • 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).	0.00% 0/67 • 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).	7.9% 7/89 • 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).
Infections and infestations Upper respiratory tract infection	1.5% 1/67 • 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).	1.5% 1/67 • 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).	10.1% 9/89 • 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).
Infections and infestations Pharyngitis	0.00% 0/67 • 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).	0.00% 0/67 • 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).	9.0% 8/89 • 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).
Respiratory, thoracic and mediastinal disorders Nasal congestion	0.00% 0/67 • 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).	0.00% 0/67 • 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).	10.1% 9/89 • 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).
Investigations Weight decreased	0.00% 0/67 • 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).	1.5% 1/67 • 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).	6.7% 6/89 • 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).

Additional Information

VP Medical Affairs, CNS

Ortho-McNeil Janssen Scientific Affairs, LLC

Phone: 609-730-2136

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place