Trial Outcomes & Findings for Adult Study / OROS Methylphenidate Hydrochloride (HCL) (OROS MPH) in Adults With Attention Deficit Hyperactivity Disorder (ADHD) (NCT NCT00937040)

NCT ID: NCT00937040

Last Updated: 2013-07-30

Results Overview

The Adult ADHD Investigator Symptom Rating Score (AISRS) assesses 18 core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms for adult subjects based on the investigator's rating for each of the symptoms using a four point scale (0=None, 1=Mild, 2=Moderate, and 3=Severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The AISRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 357 participants
• Primary outcome timeframe: Baseline, endpoint (42 days or early discontinuation)
• Results posted on: 2013-07-30

Participant Flow

Participant milestones

Measure	PLACEBO Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Overall Study STARTED	179	178
Overall Study COMPLETED	138	141
Overall Study NOT COMPLETED	41	37

Reasons for withdrawal

Measure	PLACEBO Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Overall Study Adverse Event	5	8
Overall Study Lost to Follow-up	12	12
Overall Study Protocol Violation	3	0
Overall Study Withdrawal by Subject	13	7
Overall Study NONCOMPLIANCE WITH STUDY DRUG	3	2
Overall Study POST ENROLL EXCLUSIONARY LAB(S)/ECG FIND	5	8

Baseline Characteristics

Adult Study / OROS Methylphenidate Hydrochloride (HCL) (OROS MPH) in Adults With Attention Deficit Hyperactivity Disorder (ADHD)

Baseline characteristics by cohort

Measure	PLACEBO n=179 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=178 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA	Total n=357 Participants Total of all reporting groups
Age, Categorical <=18 years	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	175 Participants n=5 Participants	173 Participants n=7 Participants	348 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Age Continuous	34.6 years STANDARD_DEVIATION 11.53 • n=5 Participants	36.8 years STANDARD_DEVIATION 11.87 • n=7 Participants	35.7 years STANDARD_DEVIATION 11.73 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	86 Participants n=7 Participants	165 Participants n=5 Participants
Sex: Female, Male Male	100 Participants n=5 Participants	92 Participants n=7 Participants	192 Participants n=5 Participants
Region of Enrollment USA	179 participants n=5 Participants	178 participants n=7 Participants	357 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set was defined as all randomized subjects who have received at least one dose of the study medication and have any post-baseline efficacy data (not including ASRS).

The Adult ADHD Investigator Symptom Rating Score (AISRS) assesses 18 core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms for adult subjects based on the investigator's rating for each of the symptoms using a four point scale (0=None, 1=Mild, 2=Moderate, and 3=Severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The AISRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Score (AISRS) Over Time Using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Fourth Edition for Diagnosis Baseline	37.0 units on a scale Standard Deviation 7.51	37.8 units on a scale Standard Deviation 6.94
Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Score (AISRS) Over Time Using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Fourth Edition for Diagnosis Change from baseline at endpoint	-11.7 units on a scale Standard Deviation 13.30	-17.1 units on a scale Standard Deviation 12.44
Adult Attention Deficit Hyperactivity Disorder (ADHD) Investigator Symptom Rating Score (AISRS) Over Time Using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) Fourth Edition for Diagnosis Endpoint	25.2 units on a scale Standard Deviation 13.47	20.7 units on a scale Standard Deviation 12.76

SECONDARY outcome

Timeframe: Baseline, 4 hour timepoint for extended days or last non-missing value for non-extended days on day 42 or early discontinuation (endpoint)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The 1st part generates basic "reaction time" to colors. The 2nd part generates "complex reaction time score" to matching color names and font color. The 3rd part establishes a "Stroop reaction time" and an error score to unmatched color names/fonts. Reaction Time Domain Score = (Stroop Complex Reaction Time Correct + Stroop Reaction Time Correct)/2. Lower scores indicate better functioning (i.e. reaction time).

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Reaction Time Domain of the Stroop Test (Cognitive and Executive Function) Endpoint (N=108,114)	653.2 milliseconds (msec) Standard Deviation 108.68	645.2 milliseconds (msec) Standard Deviation 116.56
Reaction Time Domain of the Stroop Test (Cognitive and Executive Function) Baseline (N=140,132)	708.0 milliseconds (msec) Standard Deviation 134.36	700.3 milliseconds (msec) Standard Deviation 141.09
Reaction Time Domain of the Stroop Test (Cognitive and Executive Function) Change from baseline at endpoint (N=103,101)	-39.8 milliseconds (msec) Standard Deviation 118.16	-51.2 milliseconds (msec) Standard Deviation 123.45

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The Shifting Attention Test (SAT) a computerized measure of the ability to shift from one instruction set to another quickly and accurately. The Continuous Performance Test (CPT) is a computerized measure of vigilance or sustained attention/attention over time. Vigilance Domain (Complex Attention) Score = Stroop Commission Errors + SAT Errors + CPT Commission Errors + CPT Omission Errors. Lower scores indicate better functioning (i.e. sustained attention).

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Vigilance Domain (Complex Attention) of the Stroop Test/Shifting Attention Test (SAT)/Continuous Performance Test (CPT) (Cognitive and Executive Function) Baseline (N=140,132)	28.2 errors Standard Deviation 39.43	35.7 errors Standard Deviation 47.15
Vigilance Domain (Complex Attention) of the Stroop Test/Shifting Attention Test (SAT)/Continuous Performance Test (CPT) (Cognitive and Executive Function) Endpoint (N=108,114)	27.2 errors Standard Deviation 43.97	23.9 errors Standard Deviation 37.04
Vigilance Domain (Complex Attention) of the Stroop Test/Shifting Attention Test (SAT)/Continuous Performance Test (CPT) (Cognitive and Executive Function) Change from baseline at endpoint (N=103,101)	-0.2 errors Standard Deviation 47.98	-10.4 errors Standard Deviation 45.82

SECONDARY outcome

Timeframe: Baseline, 4 hour timepoint for extended days or last non-missing value for non-extended days on day 42 or early discontinuation (endpoint)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Stroop Test is a computerized measure of inhibition/disinhibition, executive function, reaction time, and information processing. The SAT is a computerized measure of the ability to shift from one instruction set to another quickly and accurately. The scores generated by the SAT are: correct matches, errors, and response time. The testing score is a measure of cognitive flexibility. Cognitive Flexibility Domain Score = SAT Correct Responses - SAT Errors - Stroop Commission Errors. Higher scores indicate better accuracy.

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Cognitive Flexibility Domain of the Stroop/SAT Tests (Cognitive and Executive Function) Endpoint (N=108,114)	45.9 correct responses Standard Deviation 17.40	46.6 correct responses Standard Deviation 17.67
Cognitive Flexibility Domain of the Stroop/SAT Tests (Cognitive and Executive Function) Baseline (N=140,132)	34.0 correct responses Standard Deviation 21.54	31.5 correct responses Standard Deviation 21.57
Cognitive Flexibility Domain of the Stroop/SAT Tests (Cognitive and Executive Function) Change from baseline at endpoint (N=103,101)	11.3 correct responses Standard Deviation 18.86	13.9 correct responses Standard Deviation 20.34

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Symbol Digit Modalities Test (SDMT) is a computerized variant of the Wechsler Digit Symbol Substitution Test (DSST), but the position of symbols and digits is reversed. Scoring is the number of correct responses generated in 2 minutes. Processing Speed Domain = SDMT correct responses - SDMT errors. Higher scores indicate better functioning (i.e. information processing).

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Processing Speed Domain of the Symbol Digit Modalities Test (SDTM) (Cognitive and Executive Function) Baseline (N=140,132)	53.9 acccurate responses per minute Standard Deviation 12.65	52.8 acccurate responses per minute Standard Deviation 13.17
Processing Speed Domain of the Symbol Digit Modalities Test (SDTM) (Cognitive and Executive Function) Endpoint (N=109,114)	59.7 acccurate responses per minute Standard Deviation 13.23	58.8 acccurate responses per minute Standard Deviation 25.68
Processing Speed Domain of the Symbol Digit Modalities Test (SDTM) (Cognitive and Executive Function) Change from baseline at endpoint (N=104,101)	5.9 acccurate responses per minute Standard Deviation 9.14	4.9 acccurate responses per minute Standard Deviation 23.88

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The BRIEF-A is a self-reported measure (low=61, high=225, lower scores indicate higher executive functioning) capturing views of the subject's own functioning in the everyday environment. The BRIEF-A contains 75 scored items (1=never, 2=sometimes, 3=often) in 9 non-overlapping clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). The Behavioral Regulation Index (BRI), Metacognition Index (MI), and GEC are then derived.

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Global Executive Composite (GEC) Score of the Brief Rating Inventory of Executive Function for Adults (BRIEF-A) Baseline (N=168,166)	153.3 units on a scale Standard Deviation 23.22	153.7 units on a scale Standard Deviation 19.73
Global Executive Composite (GEC) Score of the Brief Rating Inventory of Executive Function for Adults (BRIEF-A) Endpoint (N=157,155)	137.9 units on a scale Standard Deviation 32.19	128.4 units on a scale Standard Deviation 28.98
Global Executive Composite (GEC) Score of the Brief Rating Inventory of Executive Function for Adults (BRIEF-A) Change from baseline at endpoint (N=153,153)	-14.5 units on a scale Standard Deviation 29.18	-25.8 units on a scale Standard Deviation 26.97

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The AIM-A is a subject-reported measure (low=0, high=100, a higher score is more favorable) to assess the overall impact and role that ADHD may have in the conduct of tasks that are expected of adults. The AIM-A is comprised of four global quality of life items, five economic impact items, and five multi-item scales that describe important concepts. Items include: Living with ADHD; General Well-Being; Work, Home and School Performance and Daily Functioning; Relationships; and Communication; and Impact of Symptoms (emotional, degree of daily interference).

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Performance and Daily Functioning Scale of the Adult ADHD Impact Module (AIM-A) Baseline (N=168,166)	36.0 units on a scale Standard Deviation 18.34	31.9 units on a scale Standard Deviation 17.45
Performance and Daily Functioning Scale of the Adult ADHD Impact Module (AIM-A) Endpoint (N=157,155)	48.5 units on a scale Standard Deviation 26.11	59.4 units on a scale Standard Deviation 24.14
Performance and Daily Functioning Scale of the Adult ADHD Impact Module (AIM-A) Change from baseline at endpoint (N=153,153)	12.7 units on a scale Standard Deviation 24.00	27.5 units on a scale Standard Deviation 26.44

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The EWPS provides a measure of the subject's report of their overall productivity (low=0, high=100, a higher score indicates worsening work productivity and efficiency). There are 25 items (questions 15-39) on the scale that describe types of behaviors/ subjective feelings that are highly likely to reduce work productivity/efficiency. These 25 items are rated on a 5-point scale (0=never, 1=rarely, 2=sometimes, 3=often, to 4=almost always) indicating how often the behavior, feeling or attitude has been manifested in the past week. The total score is the sum of the 25 items.

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Subject's Rating of Endicott Work Productivity Scale (EWPS) Endpoint (N=126,124)	33.3 units on a scale Standard Deviation 21.70	27.6 units on a scale Standard Deviation 18.53
Subject's Rating of Endicott Work Productivity Scale (EWPS) Change from baseline at endpoint (N=104,115)	-9.7 units on a scale Standard Deviation 20.58	-18.0 units on a scale Standard Deviation 18.54
Subject's Rating of Endicott Work Productivity Scale (EWPS) Baseline (N=129,141)	44.7 units on a scale Standard Deviation 19.68	46.2 units on a scale Standard Deviation 17.07

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Dyadic Adjustment Scale (DAS) assesses the relationship satisfaction or adjustment of partners in committed couple relationships. The 32-question DAS includes 4 empirically validated subscales that measure: dyadic satisfaction, dyadic consensus, dyadic cohesion and affectional expression. The response format varies across the entire scale and includes 5-, 6-, and 7-point Likert-scale questions and two yes/no items. The 10-question subset of the DAS, the Dyadic Satisfaction Subscale, was used in this study (low=0, high=50, higher score means better relationship satisfaction).

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Subject's Rating of Dyadic Satisfaction Subscale (DSS) Change from baseline at endpoint (N=46,52)	0.0 units on a scale Standard Deviation 4.88	1.4 units on a scale Standard Deviation 4.66
Subject's Rating of Dyadic Satisfaction Subscale (DSS) Baseline (N=65,80)	32.3 units on a scale Standard Deviation 6.92	31.4 units on a scale Standard Deviation 6.62
Subject's Rating of Dyadic Satisfaction Subscale (DSS) Endpoint (N=66,68)	32.5 units on a scale Standard Deviation 7.57	33.3 units on a scale Standard Deviation 6.68

SECONDARY outcome

Timeframe: Endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set for non-missing response to this question

The satisfaction with treatment questionnaire (low=0, high=20, a lower score indicates lower satisfaction with treatment) requires subjects to answer 4 questions related to how much their ADHD symptoms have changed since starting the medication, how much benefit they received from the medication, the extent, if any, the advantages outweighed the disadvantages, and overall satisfaction with the medication. The responses for this question vary with range of satisfaction (e.g. extremely satisfied, very satisfied, satisfied, neutral, dissatisfied, very dissatisfied, or extremely dissatisfied).

Outcome measures

Measure	PLACEBO n=157 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=155 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Subject's Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication You Are Taking for ADHD? Very Dissatisfied	18 Participants	17 Participants
Subject's Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication You Are Taking for ADHD? Dissatisfied	24 Participants	7 Participants
Subject's Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication You Are Taking for ADHD? Satisfied	16 Participants	40 Participants
Subject's Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication You Are Taking for ADHD? Very Satisfied	15 Participants	28 Participants
Subject's Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication You Are Taking for ADHD? Extremely Dissatisfied	39 Participants	14 Participants
Subject's Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication You Are Taking for ADHD? Neither Dissatisfied or Satisfied	38 Participants	36 Participants
Subject's Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication You Are Taking for ADHD? Extremely Satisfied	7 Participants	13 Participants

SECONDARY outcome

Timeframe: Endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set

AISRS responder rate is defined as the percentage of subjects with AISRS < 18 at endpoint.

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Responder Rate Using AISRS Responder	30.8 Percent of participants	45.0 Percent of participants
Responder Rate Using AISRS Non-responder	69.2 Percent of participants	55.0 Percent of participants

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Clinical Global Impression - Severity of Illness (CGI-S) is a clinician-rated subscale (low=0, high=7, higher score indicates increasing illness). The clinician rates the severity of the ADHD symptoms in relation to the clinician's total experience with ADHD subjects using a 7-point scale (1=normal, not at all ill, 2= borderline ill, 3= mildly ill, 4=moderately ill, 5= markedly ill, 6= severely ill, 7= among the most extremely ill subjects) in response to the question "Considering your total clinical experience with this particular population, how ill is the subject at this time?".

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Clinical Global Impression - Severity of Illness Subscale (CGI-S) Baseline	4.6 units on a scale Standard Deviation 0.69	4.7 units on a scale Standard Deviation 0.75
Clinical Global Impression - Severity of Illness Subscale (CGI-S) Endpoint (N=160,158)	3.5 units on a scale Standard Deviation 1.28	3.0 units on a scale Standard Deviation 1.37
Clinical Global Impression - Severity of Illness Subscale (CGI-S) Change from baseline at endpoint (N=160,158)	-1.1 units on a scale Standard Deviation 1.33	-1.7 units on a scale Standard Deviation 1.46

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set and non-missing values at each timepoint. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The ADHD Rating Scale-IV (Significant Other) is an 18-item list of core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms. Each item is rated on a four point Likert type scale (0 = never or rarely, 1 = sometimes, 2 = often, and 3 = very often). The subject's designated observer will complete this scale, with baseline assessment based on the subject's usual functioning when not on medication. The total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).

Outcome measures

Measure	PLACEBO n=59 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=54 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Significant Other's (a Spouse, Significant Other or Other Adult in the Household, Described in This Study as the Designated Observer) Rating of Adult ADHD Rating Scale IV Change from baseline at endpoint (N=35,28)	-1.7 units on a scale Standard Deviation 9.77	-8.3 units on a scale Standard Deviation 10.90
Significant Other's (a Spouse, Significant Other or Other Adult in the Household, Described in This Study as the Designated Observer) Rating of Adult ADHD Rating Scale IV Baseline (N=51,40)	29.9 units on a scale Standard Deviation 12.19	29.2 units on a scale Standard Deviation 12.00
Significant Other's (a Spouse, Significant Other or Other Adult in the Household, Described in This Study as the Designated Observer) Rating of Adult ADHD Rating Scale IV Endpoint (N=40,35)	27.3 units on a scale Standard Deviation 12.01	21.7 units on a scale Standard Deviation 13.75

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The BRIEF-A, as completed by the DO, is a measure (low=61, high=225, lower scores indicate higher executive functioning) capturing views of an adult informant familiar with the subject's functioning. The BRIEF-A contains 75 scored items (1=never, 2=sometimes, 3=often) in nine non-overlapping clinical scales (Inhibit, Shift, Emotional Control, Self-Monitor, Initiate, Working Memory, Plan/Organize, Task Monitor, and Organization of Materials). The Behavioral Regulation Index (BRI), Metacognition Index (MI), and Global Executive Composite (GEC) are then derived.

Outcome measures

Measure	PLACEBO n=80 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=76 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Designated Observer's (DO) Global Executive Composite (GEC) Score of the Brief Rating Inventory of Executive Function for Adults (BRIEF-A) Baseline (N=66,58)	139.3 units on a scale Standard Deviation 27.08	144.1 units on a scale Standard Deviation 24.77
Designated Observer's (DO) Global Executive Composite (GEC) Score of the Brief Rating Inventory of Executive Function for Adults (BRIEF-A) Endpoint (N=55,52)	133.3 units on a scale Standard Deviation 26.54	127.3 units on a scale Standard Deviation 27.18
Designated Observer's (DO) Global Executive Composite (GEC) Score of the Brief Rating Inventory of Executive Function for Adults (BRIEF-A) Change from baseline at endpoint (N=44,39)	-10.3 units on a scale Standard Deviation 19.79	-20.1 units on a scale Standard Deviation 26.25

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Dyadic Adjustment Scale (DAS) completed by DOs who were spouses or significant others assesses the relationship satisfaction or adjustment of partners in committed couple relationships. The 32-question DAS includes 4 empirically validated subscales that measure: dyadic satisfaction, dyadic consensus, dyadic cohesion and affectional expression. Possible responses include 5-, 6-, and 7-point Likert-scale questions and two yes/no items. The 10-question DAS subset, the Dyadic Satisfaction Subscale, was used in this study (low=0, high=50, higher score means better relationship satisfaction).

Outcome measures

Measure	PLACEBO n=80 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=76 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Designated Observer's (DO) Rating of Dyadic Satisfaction Subscale Baseline (N=44,43)	36.2 units on a scale Standard Deviation 6.75	35.8 units on a scale Standard Deviation 8.29
Designated Observer's (DO) Rating of Dyadic Satisfaction Subscale Change from baseline at endpoint (N=31,31)	0.6 units on a scale Standard Deviation 4.32	1.5 units on a scale Standard Deviation 4.16
Designated Observer's (DO) Rating of Dyadic Satisfaction Subscale Endpoint (N=43,38)	37.5 units on a scale Standard Deviation 6.08	37.2 units on a scale Standard Deviation 8.38

SECONDARY outcome

Timeframe: Endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set for non-missing response to this question

The satisfaction with treatment questionnaire (low=0, high=20, a lower score indicates lower satisfaction with treatment) requires the subject's DO to answer 4 questions related to how much the subject's ADHD symptoms have changed since starting the medication, how much benefit was received from the medication, the extent, if any, the advantages outweighed the disadvantages, and overall satisfaction with the medication. Responses vary from extremely satisfied, very satisfied, satisfied, neutral, mildly dissatisfied, dissatisfied, very dissatisfied, or extremely dissatisfied.

Outcome measures

Measure	PLACEBO n=80 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=76 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? Extremely Dissatisfied	5 Participants	2 Participants
Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? Dissatisfied	8 Participants	6 Participants
Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? Satisfied	5 Participants	10 Participants
Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? Extremely Satisfied	0 Participants	0 Participants
Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? Missing/Unknown	33 Participants	44 Participants
Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? Very Dissatisfied	4 Participants	2 Participants
Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? Neither Dissatisfied or Satisfied	19 Participants	9 Participants
Designated Observer's (DO) Rating of Satisfaction With Treatment Questionnaire - Overall, How Satisfied or Dissatisfied Are You With the Medication for ADHD Your Partner is Taking? Very Satisfied	6 Participants	3 Participants

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Adult ADHD Self-Report Scale (ASRS) assesses 18 core ADHD symptoms corresponding to the DSM-IV diagnostic symptoms for adult subjects based on the subject's own rating for each of the symptoms using a four point scale (0=None, 1=Mild, 2=Moderate, and 3=Severe). If a single item is missing the score is imputed and if more than one item is missing, the total score is treated as missing. The ASRS total score is derived by summing the score assigned to each of the 18 symptoms (low=0, high=54, a higher score signifies a greater severity of symptoms).

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Adult ADHD Self-Report Scale (ASRS) Over Time Endpoint (N=171,167)	37.5 units on a scale Standard Deviation 16.33	32.6 units on a scale Standard Deviation 16.04
Adult ADHD Self-Report Scale (ASRS) Over Time Baseline (N=167, 166)	49.8 units on a scale Standard Deviation 10.11	51.6 units on a scale Standard Deviation 9.73
Adult ADHD Self-Report Scale (ASRS) Over Time Change from baseline at endpoint (N=166, 165)	-12.1 units on a scale Standard Deviation 15.86	-19.4 units on a scale Standard Deviation 15.86

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The PSQI discriminates between good and poor sleepers. The self-administered scale contains 15 multiple-choice items concerning frequency of sleep disturbances and subjective sleep quality and 4 write-in items that inquire about typical bedtime, wake-up time, sleep latency, and sleep duration over the past month. The PSQI generates 7 scores corresponding to the different sleep domains. Each component score ranges from 0 to 3. Total sleep index is calculated by adding up the 7 component scores (low=0, high=21, the lower the score, the better in sleep quality).

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Pittsburgh Sleep Quality Index (PSQI) Total Score Baseline (N=167, 166)	8.8 units on a scale Standard Deviation 3.47	9.1 units on a scale Standard Deviation 3.17
Pittsburgh Sleep Quality Index (PSQI) Total Score Change from baseline at endpoint (N=152, 153)	-0.4 units on a scale Standard Deviation 3.00	-0.8 units on a scale Standard Deviation 2.96
Pittsburgh Sleep Quality Index (PSQI) Total Score Endpoint (N=157, 155)	8.5 units on a scale Standard Deviation 3.25	8.4 units on a scale Standard Deviation 3.14

SECONDARY outcome

Timeframe: Baseline, endpoint (42 days or early discontinuation)

Population: Intent-to-Treat (ITT) analysis set. Only non-missing values are shown at each category (timepoint). Change from baseline to endpoint requires a non-missing value at both baseline and endpoint.

The Epworth Sleepiness Scale (ESS) is an 8-item self-rated questionnaire designed to assess the overall level of daytime sleepiness. Each item describes normal daily situations (i.e., watching TV, lying down in the afternoon, sitting inactive in a public place) and subjects rate the likelihood of dozing off or falling asleep in each situation. Responses use a 4-point rating scale (0=would never doze, 1=slight chance of dozing, 2=moderate chance of dozing, 3=high chance of dozing). Item scores are summed to produce a total score (range of 0-24) with lower score suggesting more alertness.

Outcome measures

Measure	PLACEBO n=172 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=169 Participants Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Epworth Sleepiness Scale (ESS) Baseline (N=167,166)	9.1 units on a scale Standard Deviation 5.01	9.5 units on a scale Standard Deviation 4.81
Epworth Sleepiness Scale (ESS) Endpoint (N=157,155)	8.0 units on a scale Standard Deviation 5.20	7.0 units on a scale Standard Deviation 4.86
Epworth Sleepiness Scale (ESS) Change from baseline at endpoint (N=152,153)	-1.0 units on a scale Standard Deviation 4.56	-2.5 units on a scale Standard Deviation 4.13

Adverse Events

PLACEBO

Serious events: 1 serious events

Other events: 49 other events

Deaths: 0 deaths

OROS MPH

Serious events: 0 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Measure	PLACEBO n=175 participants at risk Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=174 participants at risk Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Psychiatric disorders Suicidal Ideation	0.57% 1/175	0.00% 0/174

Other adverse events

Measure	PLACEBO n=175 participants at risk Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of placebo	OROS MPH n=174 participants at risk Once daily (morning) tablet(s) taken orally of 18, 36 , 54, or 72 mg of Osmotic Release Oral System (OROS) Extended Release Methylphenidate HCl (MPH) - CONCERTA
Nervous system disorders Headache	11.4% 20/175	19.0% 33/174
Gastrointestinal disorders Nausea	4.6% 8/175	5.2% 9/174
Gastrointestinal disorders Dry Mouth	1.7% 3/175	15.5% 27/174
Infections and infestations Upper Respiratory Tract Infection	5.1% 9/175	5.2% 9/174
General disorders Irritability	3.4% 6/175	6.3% 11/174
General disorders Feeling Jittery	1.1% 2/175	6.3% 11/174
Psychiatric disorders Insomnia	2.3% 4/175	6.9% 12/174
Psychiatric disorders Initial Insomnia	1.7% 3/175	9.8% 17/174
Psychiatric disorders Anxiety	1.1% 2/175	6.9% 12/174
Metabolism and nutrition disorders Decreased Appetite	4.0% 7/175	14.4% 25/174
Cardiac disorders Palpitations	0.00% 0/175	5.7% 10/174

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 PI has the right to publish results of research and background information provided by SPONSOR necessary to include in publication of research results or for others to verify results. PI shall include a statement that creation of data was supported by SPONSOR. Prior to submission for publication/presentation, the INSTITUTION shall provide SPONSOR at least sixty (60) days for review.
• Publication restrictions are in place

Restriction type: OTHER