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

A Phase IIIb, Randomized, Double-Blind, Multi-Center, Parallel-Group, Placebo-Controlled, Dose Optimization Study, Designed to Evaluate the Efficacy and Safety of MTS in Adolescents Aged 13-17 Years With ADHD

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00499863

Enrollment

217

Registered

2007-07-12

Start date

2007-07-31

Completion date

2008-05-31

Last updated

2017-04-26

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

ADHD

Brief summary

To assess the efficacy and safety of efficacy of MTS compared to placebo

Detailed description

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.

Interventions

DRUGmethylphenidate transdermal system

dose optimization of 4 doses of the MTS transdermal patch over the same duration of wear

DRUGPlacebo

Placebo patch

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

13 Years to 17 Years

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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 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)	—
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.

Other

Measure	Time frame	Description
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.

Countries

United States

Participant flow

Pre-assignment details

217 subjects were enrolled and randomized. The study included a screening/washout period, a 5 week dose optimization period, a 2 week maintenance period, and a follow-up period.

Participants by arm

Arm	Count
Methylphenidate Transdermal System Methylphenidate Transdermal System Patch	145
Placebo (PTS) Placebo Transdermal System	72
Total	217

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	8	2
Overall Study	Lack of Efficacy	21	27
Overall Study	Lost to Follow-up	1	1
Overall Study	Protocol Violation	12	7
Overall Study	Sponsor decision	2	2
Overall Study	Withdrawal by Subject	6	4

Baseline characteristics

Characteristic	Placebo (PTS)	Methylphenidate Transdermal System	Total
Age, Categorical <=18 years	72 Participants	145 Participants	217 Participants
Age, Categorical >=65 years	0 Participants	0 Participants	0 Participants
Age, Categorical Between 18 and 65 years	0 Participants	0 Participants	0 Participants
Age, Continuous	14.6 years STANDARD_DEVIATION 1.42	14.5 years STANDARD_DEVIATION 1.25	14.6 years STANDARD_DEVIATION 1.31
Region of Enrollment United States	72 participants	145 participants	217 participants
Sex: Female, Male Female	19 Participants	36 Participants	55 Participants
Sex: Female, Male Male	53 Participants	109 Participants	162 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	125 / 145	28 / 72
serious Total, serious adverse events	1 / 145	1 / 72

Outcome results

Primary

Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Endpoint

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.

Time frame: baseline and endpoint (up to 7 weeks)

Population: Intent-to-treat (ITT) which included all randomized subjects who received at least one dose of MTS or PTS, and had one Baseline and at least one post-Baseline assessment.

Arm	Measure	Value (LEAST_SQUARES_MEAN)	Dispersion
Methylphenidate Transdermal System	Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Endpoint	-18.8 scores on a scale	Standard Error 1.01
Placebo (PTS)	Change From Baseline in the Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Total Score at Endpoint	-8.8 scores on a scale	Standard Error 1.42

Comparison: The null hypothesis was that there is no difference between MTS and placebo.p-value: <0.001ANCOVA

Secondary