Trial Outcomes & Findings for Evaluate the Efficacy &Safety of Methylphenidate Transdermal System (MTS) in Adolescents Aged 13-17 Years With ADHD (NCT NCT00499863)

NCT ID: NCT00499863

Last Updated: 2017-04-26

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 217 participants
• Primary outcome timeframe: baseline and endpoint (up to 7 weeks)
• Results posted on: 2017-04-26

Participant Flow

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.

Participant milestones

Measure	Methylphenidate Transdermal System Methylphenidate Transdermal System Patch	Placebo (PTS) Placebo Transdermal System
Overall Study STARTED	145	72
Overall Study COMPLETED	95	29
Overall Study NOT COMPLETED	50	43

Reasons for withdrawal

Measure	Methylphenidate Transdermal System Methylphenidate Transdermal System Patch	Placebo (PTS) Placebo Transdermal System
Overall Study Lack of Efficacy	21	27
Overall Study Protocol Violation	12	7
Overall Study Withdrawal by Subject	6	4
Overall Study Adverse Event	8	2
Overall Study Sponsor decision	2	2
Overall Study Lost to Follow-up	1	1

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Methylphenidate Transdermal System n=145 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System	Total n=217 Participants Total of all reporting groups
Age, Categorical <=18 years	145 Participants n=5 Participants	72 Participants n=7 Participants	217 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	14.5 years STANDARD_DEVIATION 1.25 • n=5 Participants	14.6 years STANDARD_DEVIATION 1.42 • n=7 Participants	14.6 years STANDARD_DEVIATION 1.31 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	19 Participants n=7 Participants	55 Participants n=5 Participants
Sex: Female, Male Male	109 Participants n=5 Participants	53 Participants n=7 Participants	162 Participants n=5 Participants
Region of Enrollment United States	145 participants n=5 Participants	72 participants n=7 Participants	217 participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Measure	Methylphenidate Transdermal System n=143 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo 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	-8.8 scores on a scale Standard Error 1.42

SECONDARY outcome

Timeframe: Baseline and endpoint (up to 7 weeks)

Population: ITT

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).

Outcome measures

Measure	Methylphenidate Transdermal System n=143 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Change From Baseline in the Conner's Parent Rating Scale-Revised (CPRS-R) Total Score at Endpoint	-20.9 scores on a scale Standard Error 1.45	-7.5 scores on a scale Standard Error 2.08

SECONDARY outcome

Timeframe: up to 7 weeks

Population: ITT

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.

Outcome measures

Measure	Methylphenidate Transdermal System n=143 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Improvement in Clinical Global Impressions-Improvement (CGI-I) Score	93 Participants	22 Participants

SECONDARY outcome

Timeframe: up to 7 weeks

Population: ITT

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.

Outcome measures

Measure	Methylphenidate Transdermal System n=143 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Improvement in Parent Global Assessment (PGA) Score	76 Participants	15 Participants

SECONDARY outcome

Timeframe: Baseline and endpoint (up to 7 weeks)

Population: ITT

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).

Outcome measures

Measure	Methylphenidate Transdermal System n=143 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at Endpoint	3.3 scores on a scale Standard Error 1.06	1.3 scores on a scale Standard Error 1.55

SECONDARY outcome

Timeframe: up to 7 weeks

Population: Safety population which included all randomized subjects that received at least one dose of MTS or PTS.

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.

Outcome measures

Measure	Methylphenidate Transdermal System n=145 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Dermal Response Scale (DRS) Scores	0.6 scores on a scale Standard Deviation 0.75	0.2 scores on a scale Standard Deviation 0.66

SECONDARY outcome

Timeframe: Baseline and endpoint (up to 7 weeks)

Population: Safety population

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.

Outcome measures

Measure	Methylphenidate Transdermal System n=145 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Change From Baseline in Electrocardiogram Results(QTcF Interval) at Endpoint	-1.3 msec Standard Deviation 16.70	-0.8 msec Standard Deviation 13.35

SECONDARY outcome

Timeframe: Baseline and endpoint (up to 7 weeks)

Population: Safety population

Outcome measures

Measure	Methylphenidate Transdermal System n=145 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Change From Baseline in Pulse Rate at Endpoint	6.5 bpm Standard Deviation 11.65	-1.4 bpm Standard Deviation 9.84

SECONDARY outcome

Timeframe: Baseline and endpoint (up to 7 weeks)

Population: Safety population

Outcome measures

Measure	Methylphenidate Transdermal System n=145 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Change From Baseline in Systolic Blood Pressure at Endpoint	2.0 mmHg Standard Deviation 9.44	-0.4 mmHg Standard Deviation 11.04

SECONDARY outcome

Timeframe: Baseline and endpoint (up to 7 weeks)

Outcome measures

Measure	Methylphenidate Transdermal System n=143 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Change From Baseline in Diastolic Blood Pressure at Endpoint	1.9 mmHg Standard Deviation 8.00	1.1 mmHg Standard Deviation 8.55

SECONDARY outcome

Timeframe: Baseline and endpoint (up to 7 weeks)

Population: Safety population

Outcome measures

Measure	Methylphenidate Transdermal System n=145 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Change From Baseline in Weight at Endpoint	-1.9 lbs Standard Deviation 3.87	1.77 lbs Standard Deviation 4.38

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 7 weeks

Population: Safety population (Note: not everyone in the safety population completed a sleep questionnaire)

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.

Outcome measures

Measure	Methylphenidate Transdermal System n=145 Participants Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 Participants Placebo Transdermal System
Post Sleep Questionnaire (PSQ) Quality of Sleep Average	27 Participants	13 Participants
Post Sleep Questionnaire (PSQ) Quality of Sleep Good	47 Participants	18 Participants
Post Sleep Questionnaire (PSQ) Quality of Sleep Very good	31 Participants	18 Participants
Post Sleep Questionnaire (PSQ) Quality of Sleep Very poor	2 Participants	2 Participants
Post Sleep Questionnaire (PSQ) Quality of Sleep Poor	14 Participants	7 Participants

Adverse Events

Methylphenidate Transdermal System

Serious events: 1 serious events

Other events: 125 other events

Deaths: 0 deaths

Placebo (PTS)

Serious events: 1 serious events

Other events: 28 other events

Deaths: 0 deaths

Serious adverse events

Measure	Methylphenidate Transdermal System n=145 participants at risk Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 participants at risk Placebo Transdermal System
Nervous system disorders syncope	0.69% 1/145 • Number of events 2	0.00% 0/72
Psychiatric disorders negativism	0.00% 0/145	1.4% 1/72 • Number of events 1

Other adverse events

Measure	Methylphenidate Transdermal System n=145 participants at risk Methylphenidate Transdermal System Patch	Placebo (PTS) n=72 participants at risk Placebo Transdermal System
Gastrointestinal disorders Nausea	9.7% 14/145 • Number of events 14	2.8% 2/72 • Number of events 3
Infections and infestations Upper respiratory tract infection	10.3% 15/145 • Number of events 15	9.7% 7/72 • Number of events 7
Investigations Weight decreased	5.5% 8/145 • Number of events 9	1.4% 1/72 • Number of events 1
Metabolism and nutrition disorders Decreased appetite	25.5% 37/145 • Number of events 41	1.4% 1/72 • Number of events 1
Nervous system disorders Dizziness	5.5% 8/145 • Number of events 8	1.4% 1/72 • Number of events 1
Nervous system disorders Headache	12.4% 18/145 • Number of events 20	12.5% 9/72 • Number of events 9
Psychiatric disorders Insomnia	6.2% 9/145 • Number of events 11	2.8% 2/72 • Number of events 2
Psychiatric disorders Irritability	11.0% 16/145 • Number of events 16	6.9% 5/72 • Number of events 5

Additional Information

Amaury Sanchez, Sr. Manager, Regulatory Affairs

Noven Pharmaceuticals, Inc.

Email: asanchez@noven.com

Results disclosure agreements

• Principal investigator is a sponsor employee If a multicenter publication is not submitted within twelve (12) months after conclusion, abandonment or termination of the Study at all sites, or after Sponsor confirms there shall be no multicenter Study publication, the Institution and/or such Principal Investigator may publish the results from the Institution site individually.
• Publication restrictions are in place

Restriction type: OTHER