Trial Outcomes & Findings for An Efficacy and Safety Study of Osmotic Release Oral System (OROS) Methylphenidate in Participants With Attention Deficit Hyperactivity Disorder (ADHD) (NCT NCT01012622)

Last Updated: 2014-03-14

Results Overview

K-ARS measures the 18 symptoms based on Diagnostic and Statistical Manual of Mental Disorders-forth edition (DSM-IV 1994). Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often), whereas the rating of 2 points or more was regarded as abnormal. Total scores range from 0 (no symptoms) to 54 (highly symptomatic), higher score indicates worsening of condition.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

142 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2014-03-14

Participant Flow

Participant milestones

Participant milestones
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Overall Study STARTED	142
Overall Study COMPLETED	111
Overall Study NOT COMPLETED	31

Reasons for withdrawal

Reasons for withdrawal
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Overall Study Withdrawal by Subject	6
Overall Study Lost to Follow-up	5
Overall Study Adverse Event	7
Overall Study non-compliance with the drug	9
Overall Study Other	1
Overall Study screening failure	1
Overall Study withdrawal of consent by a parent	2

Baseline Characteristics

An Efficacy and Safety Study of Osmotic Release Oral System (OROS) Methylphenidate in Participants With Attention Deficit Hyperactivity Disorder (ADHD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=136 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Age, Continuous	8.4 years STANDARD_DEVIATION 1.5 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants
Sex: Female, Male Male	112 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Intention-to-treat (ITT) population included participants who received the study drug at least once and had the primary efficacy endpoint data available

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=134 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Korean Version of the Attention-Deficit Hyperactivity Disorder (K-ADHD) Rating Scale (K-ARS) Total Score at Week 12 Baseline	33.37 units on a scale Standard Deviation 8.67
Change From Baseline in Korean Version of the Attention-Deficit Hyperactivity Disorder (K-ADHD) Rating Scale (K-ARS) Total Score at Week 12 Change at Week 12	-20.43 units on a scale Standard Deviation 10.42

PRIMARY outcome

Timeframe: Week 12

Population: ITT population included participants who received the study drug at least once and had the primary efficacy endpoint data available. "N" (Number of Participants Analyzed) represents number of participants who were evaluable for this outcome measure.

Response is defined as at least 25 percent (%) decrease in total score of K-ARS compared to baseline. K-ARS measures the 18 symptoms based on DSM-IV (1994). Individual item scores range from 0 (none/never or rarely) to 3 (severe/very often), whereas the rating of 2 points or more was regarded as abnormal. Total scores range from 0 (no symptoms) to 54 (highly symptomatic), higher score indicates worsening of condition.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=127 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Number of Participants With Response Based on K-ARS Total Score at Week 12	118 participants

PRIMARY outcome

Timeframe: Week 12

Remission is defined by all of the following criteria; 1) K-ARS Total score of 18 or less. 2) "Very much improved" or "Much improved" in CGI-I. K-ARS total score ranges from 0 (no symptoms) to 54 (highly symptomatic), higher score indicates worsening of condition. CGI-I is a 7-point scale ranging from 1 to 7, where 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse, higher score indicates worsening of condition.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=127 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Number of Participants With Remission Based on K-ARS Total Score and Clinical Global Impression - Improvement (CGI-I) Scale Score at Week 12	99 participants

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included participants who took study drug at least once and had primary efficacy endpoint data available. Last Observation Carried Forward (LOCF) method was used. "n" signifies participants who were evaluated for each specified category for this measure.

CHIP was designed to assess the physical, psychological health conditions and functional well-being of children. The instrument has sub-domains such satisfaction (11 items) ranges from 0 to 44, stability (22 items) ranges from 0 to 88, elasticity (19 items) ranges from 0 to 76, risk aversion (14 items) ranges from 0 to 56, achievement (10 items) ranges from 0 to 40. Good health is in the range from 44 to 56 points for all sub-domains. A score of 43 or below indicates poor health in that domain. A score of 57 or higher indicates excellent health. The total score is an average of the scores for the 5 domains and ranges from 0 to 304. Higher total score indicates better health.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=134 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Risk aversion:Change at Week 12 (n=132)	5.73 units on a scale Standard Deviation 7.27
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Total Score:Baseline (n=126)	207.85 units on a scale Standard Deviation 26.62
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Total Score:Change at Week 12 (n=126)	18.08 units on a scale Standard Deviation 22.54
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Satisfaction:Baseline (n=132)	26.17 units on a scale Standard Deviation 7.20
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Satisfaction:Change at Week 12 (n=132)	2.27 units on a scale Standard Deviation 5.89
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Stability:Baseline (n=129)	82.13 units on a scale Standard Deviation 11.18
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Stability:Change at Week 12 (n=129)	4.47 units on a scale Standard Deviation 10.87
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Elasticity:Baseline (n=132)	38.30 units on a scale Standard Deviation 8.22
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Elasticity:Change at Week 12 (n=132)	2.53 units on a scale Standard Deviation 7.10
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Risk aversion:Baseline (n=132)	40.67 units on a scale Standard Deviation 7.91
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Achievement:Baseline (n=133)	21.00 units on a scale Standard Deviation 6.16
Change From Baseline in Child Health and Illness Profile-Child Edition (CHIP) Total Score and 5 Sub-domains Score at Week 12 Achievement:Change at Week 12 (n=133)	2.45 units on a scale Standard Deviation 5.07

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included participants who received the study drug at least once and had the primary efficacy endpoint data available. LOCF method was used. "N" (Number of Participants Analyzed) represents number of participants who were evaluable for this outcome measure.

CAT was developed to properly reflect brain function in childhood. It provided measurement of simple visual selective attention in terms of omission (number of missing response to target stimulus \[0-150\], higher score indicate greater omission), false alarm (number of response to non-target stimulus \[0-150\], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus \[200-1100, low score means faster response to target stimulus\]), Response (consistency of response time to target stimulus \[30-650, Low score means good consistency of response\]).

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=118 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Omission:Change at Week 12	-4.53 units on a scale Standard Deviation 17.94
Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 False alarm:Baseline	17.42 units on a scale Standard Deviation 18.48
Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response:Baseline	201.05 units on a scale Standard Deviation 105.78
Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response:Change at Week 12	-48.36 units on a scale Standard Deviation 111.02
Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Omission:Baseline	8.79 units on a scale Standard Deviation 15.77
Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 False alarm:Change at Week 12	-5.03 units on a scale Standard Deviation 13.43
Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response mean:Baseline	501.32 units on a scale Standard Deviation 130.80
Change From Baseline in Visual Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response mean:Change at Week 12	-37.41 units on a scale Standard Deviation 110.34

SECONDARY outcome

Timeframe: Baseline and Week 12

CAT was developed to properly reflect brain function in childhood. It provided measurement of simple auditory selective attention in terms of omission (number of missing response to target stimulus \[0-150\], higher score indicate greater omission), false alarm (number of response to non-target stimulus \[0-150\], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus \[200-1100, low score means faster response to target stimulus\]), Response (consistency of response time to target stimulus \[30-650, Low score means good consistency of response\]).

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=118 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Omission:Baseline	10.31 units on a scale Standard Deviation 16.52
Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Omission:Change at Week 12	-6.27 units on a scale Standard Deviation 15.88
Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 False alarm:Baseline	12.07 units on a scale Standard Deviation 14.41
Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 False alarm:Change at Week 12	-3.61 units on a scale Standard Deviation 11.86
Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response mean:Baseline	623.95 units on a scale Standard Deviation 188.38
Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response mean:Change at Week 12	-55.34 units on a scale Standard Deviation 155.36
Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response:Baseline	265.69 units on a scale Standard Deviation 108.76
Change From Baseline in Auditory Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response:Change at Week 12	-63.76 units on a scale Standard Deviation 114.15

SECONDARY outcome

Timeframe: Baseline and Week 12

CAT was developed to properly reflect brain function in childhood. It provided measurement of simple inhibition-sustained attention in terms of omission(number of missing response to target stimulus \[0-150\], higher score indicate greater omission), false alarm(number of response to non-target stimulus \[0-150\], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus \[200-1100, low score means faster response to target stimulus\]), Response (consistency of response time to target stimulus \[30-650, Low score means good consistency of response\]).

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=119 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 False alarm:Change at Week 12	-7.54 units on a scale Standard Deviation 14.19
Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Omission:Baseline	35.78 units on a scale Standard Deviation 46.91
Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Omission:Change at Week 12	-20.39 units on a scale Standard Deviation 45.40
Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 False alarm:Baseline	27.73 units on a scale Standard Deviation 15.58
Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response mean:Baseline	576.55 units on a scale Standard Deviation 147.13
Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response mean:Change at Week 12	-34.44 units on a scale Standard Deviation 140.43
Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response:Baseline	273.78 units on a scale Standard Deviation 121.94
Change From Baseline in Inhibition-Sustained Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response:Change at Week 12	-66.85 units on a scale Standard Deviation 127.13

SECONDARY outcome

Timeframe: Baseline and Week 12

CAT was developed to properly reflect brain function in childhood. It provided measurement of simple interference-selective attention in terms of omission(number of missing response to target stimulus\[0-150\], higher score indicate greater omission), false alarm(number of response to non-target stimulus\[0-150\], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus \[200-1100, low score means faster response to target stimulus\]), Response (consistency of response time to target stimulus \[30-650, Low score means good consistency of response\]).

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=119 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Omission:Baseline	20.39 units on a scale Standard Deviation 24.44
Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Omission:Change at Week 12	-10.83 units on a scale Standard Deviation 20.10
Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 False alarm:Baseline	26.03 units on a scale Standard Deviation 18.30
Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 False alarm:Change at Week 12	-6.14 units on a scale Standard Deviation 16.75
Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response mean:Baseline	648.48 units on a scale Standard Deviation 171.84
Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response mean:Change at Week 12	-54.35 units on a scale Standard Deviation 134.26
Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response:Baseline	276.74 units on a scale Standard Deviation 156.70
Change From Baseline in Interference-Selective Attention Subtest of Comprehensive Attention Test (CAT) Total Score at Week 12 Response:Change at Week 12	-72.18 units on a scale Standard Deviation 148.01

SECONDARY outcome

Timeframe: Baseline and Week 12

CAT was developed to properly reflect brain function in childhood. It provided measurement of simple divided attention in terms of omission(number of missing response to target stimulus\[0-150\], higher score indicate greater omission), false alarm(number of response to non-target stimulus\[0-150\], higher score indicate greater false alarm), response mean (average time spent to response to target stimulus \[200-1100, low score means faster response to target stimulus\]), Response (consistency of response time to target stimulus \[30-650, Low score means good consistency of response\]).

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=59 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 Omission:Baseline	16.05 units on a scale Standard Deviation 9.69
Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 Omission:Change at Week 12	-4.07 units on a scale Standard Deviation 10.18
Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 False alarm:Baseline	16.03 units on a scale Standard Deviation 12.36
Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 False alarm:Change at Week 12	-4.73 units on a scale Standard Deviation 9.44
Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 Response mean:Baseline	749.01 units on a scale Standard Deviation 196.66
Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 Response mean:Change at Week 12	-27.14 units on a scale Standard Deviation 186.70
Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 Response:Baseline	349.60 units on a scale Standard Deviation 130.41
Change From Baseline in Divided Attention Subtest of Comprehensive Attention Test (CAT) at Week 12 Response:Change at Week 12	-43.90 units on a scale Standard Deviation 118.84

SECONDARY outcome

Timeframe: Baseline and Week 12

CAT was developed to properly reflect brain function in childhood. The test battery provided a comprehensive measurement of simple visual auditory attention, interventional visual-auditory selective attention, divided attention, continuous attention, and operational memory. Working memory forward was measured in terms of width of space and number of correct responses ranging from 0 to 10. For width of space boxes were presented on the screen and participants remembered the order of presented box. Participants pressed the box using mouse in the forward order. Maximum number that participants correctly memorized box in the screen in the respective order was reported and overall number of times a participant responded correctly was also reported.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=59 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Working Memory Forward Subtest of Comprehensive Attention Test (CAT) at Week 12 Baseline:Width of space	4.46 correct responses Standard Deviation 1.53
Change From Baseline in Working Memory Forward Subtest of Comprehensive Attention Test (CAT) at Week 12 Baseline:Number of correct responses	5.76 correct responses Standard Deviation 2.34
Change From Baseline in Working Memory Forward Subtest of Comprehensive Attention Test (CAT) at Week 12 Change at Week 12:Number of correct responses	0.63 correct responses Standard Deviation 2.56
Change From Baseline in Working Memory Forward Subtest of Comprehensive Attention Test (CAT) at Week 12 Change at Week 12:Width of space	0.25 correct responses Standard Deviation 1.78

SECONDARY outcome

Timeframe: Baseline and Week 12

CAT was developed to properly reflect brain function in childhood. The test battery provided a comprehensive measurement of simple visual auditory attention, interventional visual-auditory selective attention, divided attention, continuous attention, and operational memory. Working memory forward was measured in terms of width of space and number of correct responses ranging from 0 to 10. For width of space boxes were presented on the screen and participants remembered the order of presented box. Participants pressed the box using mouse in the backward order. Maximum number that participants correctly memorized box in the screen in the respective order was reported and overall number of times a participant responded correctly was also reported.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=59 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Working Memory Backward Subtest of Comprehensive Attention Test (CAT) at Week 12 Baseline:Spatial span	3.63 correct responses Standard Deviation 2.06
Change From Baseline in Working Memory Backward Subtest of Comprehensive Attention Test (CAT) at Week 12 Change at Week 12:Spatial span	1.24 correct responses Standard Deviation 1.98
Change From Baseline in Working Memory Backward Subtest of Comprehensive Attention Test (CAT) at Week 12 Baseline:Number of correct responses	4.22 correct responses Standard Deviation 2.79
Change From Baseline in Working Memory Backward Subtest of Comprehensive Attention Test (CAT) at Week 12 Change at Week 12:Number of correct responses	1.86 correct responses Standard Deviation 3.02

SECONDARY outcome

Timeframe: Baseline and Week 12

APRS scale measures four factors in elementary school children such as learning ability, academic performance, impulse control, and social withdrawal. In particular, it is excellent in assessing drug effect on the academic performance not measured by other scales. Score ranges from 19 to 95, higher score means better academic performance.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=125 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Academic Performance Rating Scale (APRS) Score at Week 12 Baseline	55.46 units on a scale Standard Deviation 12.77
Change From Baseline in Academic Performance Rating Scale (APRS) Score at Week 12 Change at Week 12	7.40 units on a scale Standard Deviation 9.86

SECONDARY outcome

Timeframe: Baseline and Week 12

Beck Depression Inventory (BDI) consisted of 21 items for measuring the subjective severity of depression and emotional, cognitive, motivational, physiological symptoms of depression. Each question has a set of 4 possible answer choices, ranging in intensity, each answer being scored on a scale value of 0 (no symptom) to 3 (the most severe symptom). Accordingly, the total score ranges from 0 (no symptom) to 63 (the most severe symptom) for 21 questions.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=127 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Beck Depression Inventory (BDI) Score at Week 12 Change at Week 12	-1.89 units on a scale Standard Deviation 6.59
Change From Baseline in Beck Depression Inventory (BDI) Score at Week 12 Baseline	11.69 units on a scale Standard Deviation 7.79

SECONDARY outcome

Timeframe: Baseline and Week 12

Parenting Stress Index (PSI) was designed to assess parent or guardian child-rearing stress index on a 5-rating scale from "never" to "very truly". Out of 30 items, 20 items are scored, being consisted of 8 child characteristics-related stress items; 9 parent-child interaction-related stress items; and 3 achievement expectation-related stress items. A possible total score ranges from 20 to 100; Increase in score indicates higher stress perceived by the parent.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=123 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Parenting Stress Index (PSI) Total Score at Week 12 Baseline	58.20 units on a scale Standard Deviation 9.33
Change From Baseline in Parenting Stress Index (PSI) Total Score at Week 12 Change at Week 12	-5.25 units on a scale Standard Deviation 9.01

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: ITT population included participants who received the study drug at least once and had the primary efficacy endpoint data available. LOCF method was used.

The CGI-S rating scale is a 7 point global assessment that measures the clinician's impression of the severity of illness exhibited by a participant. A rating of 1 is equivalent to "Normal, not at all ill" and a rating of 7 is equivalent to "Among the most extremely ill participants". Higher change scores indicate worsening.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=134 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Change From Baseline in Clinical Global Impression-severity (CGI-S) Score at Week 12 Baseline	5.14 units on a scale Standard Deviation 0.90
Change From Baseline in Clinical Global Impression-severity (CGI-S) Score at Week 12 Change at Week 12	-2.51 units on a scale Standard Deviation 1.36

SECONDARY outcome

Timeframe: Week 12

The CGI-I is a 7-point scale that requires the clinician to assess how much the participant's illness has improved or worsened relative to a baseline state at the beginning of the intervention and rated as: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse. Improved very much, Improved much and Improved a little are defined as improvement and No change, Aggravated a little, Aggravated much and Aggravated very much were defined as aggravation.

Outcome measures

Outcome measures
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=129 Participants OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Clinical Global Impression - Improvement (CGI-I) Scale Score at Week 12 Improvement	122 participants
Clinical Global Impression - Improvement (CGI-I) Scale Score at Week 12 Aggravation	7 participants

Adverse Events

Osmotic Release Oral System (OROS) Methylphenidate HCL

Serious events: 0 serious events

Other events: 112 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Osmotic Release Oral System (OROS) Methylphenidate HCL n=136 participants at risk OROS methylphenidate hydrochloride (HCL) was given orally once daily at an initial dose of 18 milligram (mg) for participants below 30 Kilogram (kg) and 27 mg for those over 30 kg of body weight. The dose was increased by 9 mg or 18 mg every week for up to Week 8, followed by a maximum maintenance dose of 54 mg orally once daily up to Week 12 during which the dose can be decreased by 9 mg depending on tolerability.
Infections and infestations Otitis media	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Infections and infestations Otitis media chronic	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Infections and infestations Urinary tract infection	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Infections and infestations Varicella	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	2.9% 4/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis atopic	2.2% 3/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders Dermatitis contact	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders Hyperhidrosis	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders Rash	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders Excessive eye blinking	3.7% 5/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Skin and subcutaneous tissue disorders Eye pain	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Investigations Weight decreased	2.9% 4/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
General disorders Crying	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
General disorders Inflammation	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
General disorders Irritability	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Congenital, familial and genetic disorders Ear malformation	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Congenital, familial and genetic disorders Ventricular septal defect	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Renal and urinary disorders Enuresis	1.5% 2/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Sneezing	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Ear and labyrinth disorders Deafness neurosensory	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Injury, poisoning and procedural complications Scratch	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Surgical and medical procedures Depilation	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Insomnia	48.5% 66/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Anxiety	37.5% 51/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Decreased interest	30.1% 41/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Communication disorder	27.2% 37/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Onychophagia	27.2% 37/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Daydreaming	22.8% 31/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Nightmare	15.4% 21/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Depressed mood	13.2% 18/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Tic	8.1% 11/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Nervousness	6.6% 9/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Sleep disorder	2.9% 4/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Depression	2.2% 3/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Hostility	2.2% 3/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Agitation	1.5% 2/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Euphoric mood	1.5% 2/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Acute stress disorder	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Psychiatric disorders Logorrhoea	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	60.3% 82/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	31.6% 43/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Gastrointestinal disorders Nausea	12.5% 17/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Gastrointestinal disorders Dyspepsia	2.2% 3/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Gastrointestinal disorders Vomiting	2.2% 3/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Gastrointestinal disorders Constipation	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Gastrointestinal disorders Stomatitis	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Nervous system disorders Headache	30.1% 41/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Nervous system disorders Somnolence	23.5% 32/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Nervous system disorders Dizziness	14.0% 19/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Nervous system disorders Movement disorder	2.2% 3/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Nervous system disorders Hypersomnia	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Nervous system disorders Tremor	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Infections and infestations Nasopharyngitis	8.1% 11/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Infections and infestations Rhinitis	2.2% 3/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	1.5% 2/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.
Infections and infestations Gastroenteritis	0.74% 1/136 • From signing of informed consent form until 30 days from the completion of assessments after the administration of the last study medication (follow-up) or the point of time of dropout Safety Population included all participants who took at least one dose of study drug.

Additional Information

Clinical Research Associate

Janssen Korea MAF, Korea

Phone: 82-2-2094-4837

Results disclosure agreements

Principal investigator is a sponsor employee Principal Investigator cannot provide any trial related information to external parties' without mutual agreement with the sponsor. This is valid even after the contract is cancelled.
Publication restrictions are in place

Restriction type: OTHER