Evaluate the Efficacy &Safety of Methylphenidate Transdermal System (MTS) in Adolescents Aged 13-17 Years With ADHD

To assess the efficacy and safety of efficacy of MTS compared to placebo, as determined by the change in the clinician completed ADHD Rating Scale - Version 4th Edition (ADHD-RS-IV), in the symptomatic treatment of adolescents (aged 13-17 years) diagnosed with ADHD.

• methylphenidate transdermal system (Drug), also known as DAYTRANA: dose optimization of 4 doses of the MTS transdermal patch over the same duration of wear
• Placebo (Drug), also known as Sham treatment: Placebo patch

Primary outcomes

• Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Endpoint [baseline and endpoint (up to 7 weeks)]: The Attention Deficit Hyperactivity Disorder Rating Scale-fourth edition (ADHD-RS-IV) consists of 18 items scored on a 4-point scale ranging from 0 (no symptoms) to 3 (severe symptoms) with total score ranging from 0 to 54.

Secondary outcomes

• Change From Baseline in the Conner's Parent Rating Scale-Revised (CPRS-R) Total Score at Endpoint [Baseline and endpoint (up to 7 weeks)]: The Conner's Parent rating Scale-revised short version (CPRS-R) consists of 27 questions graded on a scale from 0 (not true at all) to 3 (very much true).
• Improvement in Clinical Global Impressions-Improvement (CGI-I) Score [up to 7 weeks]: Clinical Global Impression-Improvement (CGI-I) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement includes a score of 1 (very much improved) or 2 (much improved) on the scale.
• Improvement in Parent Global Assessment (PGA) Score [up to 7 weeks]: Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement includes a score of 1 (very much improved) or 2 (much improved) on the scale.
• Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at Endpoint [Baseline and endpoint (up to 7 weeks)]: The Youth Quality of Life Instrument-research version (YQOL-R) is a validated 56-item generic instrument for comparing quality of life of adolescents across condition groups that scores each question on a scale from 0 (never) to 4 (very often).
• Dermal Response Scale (DRS) Scores [up to 7 weeks]: Mean dermal reaction scores were graded on a scale ranging from 0 (no irritation) to 7 (strong reaction) for observed findings of erythema, edema, papules, and vesicles.
• Change From Baseline in Electrocardiogram Results(QTcF Interval) at Endpoint [Baseline and endpoint (up to 7 weeks)]: QTcF is the QT interval using Fridericia's correction formula. QT interval is a measure of time between the start of the Q wave and the end of the T wave and is dependent on the heart rate(e.g., the faster the heart rate, the shorter the QT interval). The QT interval has to be corrected in order to aid interpretation.
• Change From Baseline in Pulse Rate at Endpoint [Baseline and endpoint (up to 7 weeks)]
• Change From Baseline in Systolic Blood Pressure at Endpoint [Baseline and endpoint (up to 7 weeks)]
• Change From Baseline in Diastolic Blood Pressure at Endpoint [Baseline and endpoint (up to 7 weeks)]
• Change From Baseline in Weight at Endpoint [Baseline and endpoint (up to 7 weeks)]

Other outcomes

• Post Sleep Questionnaire (PSQ) Quality of Sleep [up to 7 weeks]: Post Sleep Questionnaire (PSQ) overall rating of quality of sleep. There are 5 rating responses ranging from very poor to very good. No numbers are associated with the rating responses.

Sex: All, ages: 13 Years to 17 Years

Inclusion Criteria:

1. Subject must meet criteria for a primary diagnosis of ADHD based on a detailed psychiatric evaluation.
2. Subject must have a total score of ≥26 on the ADHD-RS-IV at the Baseline Visit (Visit 2).
3. Subject must have a minimum level of intellectual functioning, as determined by an IQ (based on Kaufman Brief Intelligence Test \[KBIT\]) score of 80 or above.
4. Subject has blood pressure measurements within the 95th percentile for age, gender, and height at Screening and Baseline.
5. Subject is a male or female aged 13 17 years.
6. Females must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test at Screening and a negative urine pregnancy test at Baseline and agree to use acceptable contraceptives throughout the study period and for 30 days after the last dose of IP.

Exclusion Criteria:

1. Subject has a current, controlled (requiring a restricted medication) or uncontrolled, with significant symptoms such as Post Traumatic Stress Disorder, psychosis, bipolar illness, pervasive developmental disorder, severe obsessive compulsive disorder, severe depressive or severe anxiety disorder.
2. Subjects who, in the opinion of the Investigator, are acutely at risk for suicidal or violent behavior towards him/herself or others, or a history of a suicide attempt requiring medical intervention.
3. Subject is overweight.
4. Subject has a history of seizures during the last 2 years, a tic disorder, a current diagnosis and/or family history of Tourette's Disorder.
5. Subject has Conduct Disorder.
6. Subject has a positive urine drug or alcohol result at Screening (with the exception of subject's current stimulant therapy, if any).
7. Subject has a history of alcohol or other substance abuse or dependence.
8. Subject has taken an investigational drug within 30 days prior to screening.
9. Subject has any abnormal thyroid function.
10. Subject has any clinically significant laboratory abnormalities.
11. Subject has severe allergic rhinitis, disability, or other condition that might confound the results of safety assessments administered in the study or that might increase risk to the subject. Mild, stable asthma is not exclusionary.
12. The female subject is pregnant or lactating.
13. Subject has any skin disease, or history of any chronic skin disease, skin cancer, skin manifestations of allergic disease, or other dermatologic conditions which would interfere with trial assessments or compromise subject safety (e.g. dermatitis, eczema or psoriasis).
14. Subject has sensitive-skin syndrome (definition: subjects who often develop nonspecific skin irritancy reactions to bland materials) or has sensitivities to the ingredients in soaps, lotions, cosmetics or adhesives.
15. Subject has clinical signs and symptoms of skin irritation (i.e., pruritus, burning, erythema) or scars or tattoos.

Participant flow

Outcome results

• Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Endpoint (Primary), Least squares mean, scores on a scale: Methylphenidate Transdermal System -18.8 +/- 1.01; Placebo (PTS) -8.8 +/- 1.42 (p < 0.001)
• Change From Baseline in the Conner's Parent Rating Scale-Revised (CPRS-R) Total Score at Endpoint (Secondary), Least squares mean, scores on a scale: Methylphenidate Transdermal System -20.9 +/- 1.45; Placebo (PTS) -7.5 +/- 2.08 (p < 0.001)
• Improvement in Clinical Global Impressions-Improvement (CGI-I) Score (Secondary), Number, Participants: Methylphenidate Transdermal System 93; Placebo (PTS) 22 (p < 0.001)
• Improvement in Parent Global Assessment (PGA) Score (Secondary), Number, Participants: Methylphenidate Transdermal System 76; Placebo (PTS) 15 (p < 0.001)
• Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at Endpoint (Secondary), Least squares mean, scores on a scale: Methylphenidate Transdermal System 3.3 +/- 1.06; Placebo (PTS) 1.3 +/- 1.55 (p 0.288)
• Post Sleep Questionnaire (PSQ) Quality of Sleep (Other pre specified), Number, Participants: Methylphenidate Transdermal System 2; Placebo (PTS) 2
• Dermal Response Scale (DRS) Scores (Secondary), Mean, scores on a scale: Methylphenidate Transdermal System 0.6 +/- 0.75; Placebo (PTS) 0.2 +/- 0.66
• Change From Baseline in Electrocardiogram Results(QTcF Interval) at Endpoint (Secondary), Mean, msec: Methylphenidate Transdermal System -1.3 +/- 16.70; Placebo (PTS) -0.8 +/- 13.35
• Change From Baseline in Pulse Rate at Endpoint (Secondary), Mean, bpm: Methylphenidate Transdermal System 6.5 +/- 11.65; Placebo (PTS) -1.4 +/- 9.84
• Change From Baseline in Systolic Blood Pressure at Endpoint (Secondary), Mean, mmHg: Methylphenidate Transdermal System 2.0 +/- 9.44; Placebo (PTS) -0.4 +/- 11.04
• Change From Baseline in Diastolic Blood Pressure at Endpoint (Secondary), Mean, mmHg: Methylphenidate Transdermal System 1.9 +/- 8.00; Placebo (PTS) 1.1 +/- 8.55
• Change From Baseline in Weight at Endpoint (Secondary), Mean, lbs: Methylphenidate Transdermal System -1.9 +/- 3.87; Placebo (PTS) 1.77 +/- 4.38

Adverse events

Serious adverse events by term

Other adverse events by term

• Results publication: Findling RL, Turnbow J, Burnside J, Melmed R, Civil R, Li Y. A randomized, double-blind, multicenter, parallel-group, placebo-controlled, dose-optimization study of the methylphenidate transdermal system for the treatment of ADHD in adolescents. CNS Spectr. 2010 Jul;15(7):419-30. doi: 10.1017/s1092852900000353. PMID 20625364

• Robert L Finding, MD, Principal investigator, University Hospitals Cleveland Medical Center