Trial Outcomes & Findings for Evaluate the Safety and Efficacy of Methylphenidate Transdermal System (MTS) in Adolescents Aged 13-17 Years With ADHD (NCT NCT00501293)

NCT ID: NCT00501293

Last Updated: 2017-04-26

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 163 participants
• Primary outcome timeframe: Baseline and 6 months
• Results posted on: 2017-04-26

Participant Flow

Open-label, extension study of Methylphenidate Transdermal System (MTS) in subjects who had previously received study medication (MTS or placebo) in the antecedent study, SPD485-409 (NCT00499863). Upon entry into this study (SPD485-410), all subjects received MTS treatment regardless of the study treatment they had received in study SPD485-409.

The study consisted of a dose optimization period (approx. 5 weeks) and a maintenance period (5 months). Methylphenidate Transdermal System (MTS)(10, 15, 20 or 30 mg / 9 hour dose patch) was applied once-daily on the alternating hip for a 9-hour wear time. One subject in the MTS group was enrolled in error and was removed prior to receiving drug.

Participant milestones

Measure	Antecedent Methylphenidate Transdermal System (MTS) Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Optimization Period STARTED	110	53
Optimization Period COMPLETED	109	53
Optimization Period NOT COMPLETED	1	0
Maintenance Period STARTED	109	53
Maintenance Period COMPLETED	63	25
Maintenance Period NOT COMPLETED	46	28

Reasons for withdrawal

Measure	Antecedent Methylphenidate Transdermal System (MTS) Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Optimization Period Enrolled in error	1	0
Maintenance Period Withdrawal by Subject	14	13
Maintenance Period Lost to Follow-up	12	7
Maintenance Period Adverse Event	6	6
Maintenance Period Protocol Violation	2	1
Maintenance Period Lack of Efficacy	4	1
Maintenance Period Noncompliant with study medication	5	0
Maintenance Period Went into rehabilitation	1	0
Maintenance Period Would not wear patch	1	0
Maintenance Period Application site reaction	1	0

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=110 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=53 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Total n=163 Participants Total of all reporting groups
Age, Categorical <=18 years	110 Participants n=5 Participants	53 Participants n=7 Participants	163 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 1.18 • n=5 Participants	14.5 years STANDARD_DEVIATION 1.37 • n=7 Participants	14.5 years STANDARD_DEVIATION 1.24 • n=5 Participants
Sex: Female, Male Female	27 Participants n=5 Participants	14 Participants n=7 Participants	41 Participants n=5 Participants
Sex: Female, Male Male	83 Participants n=5 Participants	39 Participants n=7 Participants	122 Participants n=5 Participants
Region of Enrollment United States	110 participants n=5 Participants	53 participants n=7 Participants	163 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: Safety population defined as all subjects that received at least one dose of MTS.

Outcome measures

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=109 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=53 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Systolic Blood Pressure Baseline measure	113.4 mmHg Standard Deviation 9.59	113.0 mmHg Standard Deviation 11.20
Systolic Blood Pressure 6 months	115.3 mmHg Standard Deviation 9.91	115.9 mmHg Standard Deviation 14.82

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: Safety population

Outcome measures

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=109 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=53 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Diastolic Blood Pressure Baseline measure	69.4 mmHg Standard Deviation 7.42	67.2 mmHg Standard Deviation 7.69
Diastolic Blood Pressure 6 months	67.9 mmHg Standard Deviation 7.79	68.9 mmHg Standard Deviation 8.28

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: Safety population

Outcome measures

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=109 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=53 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Pulse Rate Baseline measure	80.4 beats per minute Standard Deviation 11.34	74.3 beats per minute Standard Deviation 9.73
Pulse Rate 6 months	81.7 beats per minute Standard Deviation 11.60	78.9 beats per minute Standard Deviation 12.27

PRIMARY outcome

Timeframe: Baseline and 6 months

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	Antecedent Methylphenidate Transdermal System (MTS) n=108 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=52 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Electrocardiogram Results (QTcF Interval) Baseline measure	391.8 msec Standard Deviation 20.76	393.2 msec Standard Deviation 17.85
Electrocardiogram Results (QTcF Interval) 6 months	395.3 msec Standard Deviation 21.22	393.5 msec Standard Deviation 21.53

PRIMARY outcome

Timeframe: 6 months

Population: Safety Population

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	Antecedent Methylphenidate Transdermal System (MTS) n=91 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=38 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Post Sleep Questionnaire (PSQ) Quality of Sleep Very poor	1 Participants	1 Participants
Post Sleep Questionnaire (PSQ) Quality of Sleep Poor	6 Participants	3 Participants
Post Sleep Questionnaire (PSQ) Quality of Sleep Average	34 Participants	10 Participants
Post Sleep Questionnaire (PSQ) Quality of Sleep Good	27 Participants	15 Participants
Post Sleep Questionnaire (PSQ) Quality of Sleep Very Good	23 Participants	9 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months

Population: Safety population

Outcome measures

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=109 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=53 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Weight Baseline measure	127.05 lb Standard Deviation 24.003	131.95 lb Standard Deviation 29.862
Weight 6 months	134.55 lb Standard Deviation 25.575	124.78 lb Standard Deviation 29.083

PRIMARY outcome

Timeframe: 6 months

Population: Safety Population

Dermal reactions 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	Antecedent Methylphenidate Transdermal System (MTS) n=162 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Dermal Reactions 0 (No evidence of irritation)	23 Participants	—
Dermal Reactions 1 (Minimal erythema)	42 Participants	—
Dermal Reactions 2 (Definite erythema)	82 Participants	—
Dermal Reactions 3 (Erythema and papules)	6 Participants	—
Dermal Reactions 4 (Definite edema)	0 Participants	—
Dermal Reactions 5 (Erythema, edema, and papules)	4 Participants	—
Dermal Reactions 6 (Vesicular eruption)	0 Participants	—
Dermal Reactions 7 (Strong reaction beyond test site)	0 Participants	—
Dermal Reactions No dermal evaluation	5 Participants	—

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: Intent-to-treat (ITT) defined as subjects who were enrolled and received at least one dose of MTS and had at least one assessment of the primary efficacy endpoint.

The 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	Antecedent Methylphenidate Transdermal System (MTS) n=106 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=52 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Scores at 6 Months Baseline measure	16.0 Units on a scale Standard Deviation 12.00	27.4 Units on a scale Standard Deviation 12.91
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Scores at 6 Months 6 months	13.5 Units on a scale Standard Deviation 10.55	14.5 Units on a scale Standard Deviation 9.53
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Scores at 6 Months Change from baseline at 6 months	-2.6 Units on a scale Standard Deviation 11.80	-12.9 Units on a scale Standard Deviation 15.20

SECONDARY outcome

Timeframe: Baseline and 6 months

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) with a total score ranging from 0 to 81. Higher scores are indicative of increased ADHD. This scale allows parents to respond on the basis of the child's behavior and help assess ADHD and evaluate problem behavior.

Outcome measures

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=105 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=52 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) at 6 Months Baseline measure	26.5 Units on a scale Standard Deviation 18.22	42.3 Units on a scale Standard Deviation 16.94
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) at 6 Months 6 months	22.5 Units on a scale Standard Deviation 16.68	24.6 Units on a scale Standard Deviation 12.92
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) at 6 Months Change from baseline at 6 months	-3.9 Units on a scale Standard Deviation 17.91	-17.7 Units on a scale Standard Deviation 20.10

SECONDARY outcome

Timeframe: 6 months

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 is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.

Outcome measures

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=106 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=52 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores	81 Participants	39 Participants

SECONDARY outcome

Timeframe: 6 months

Population: ITT

Parent Global Assessment (PGA) consists of a 7-point scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved) or 2 (much improved) on the scale.

Outcome measures

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=106 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=52 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Number of Participants With Improvement on Parent Global Assessment (PGA) Scores.	69 Participants	31 Participants

SECONDARY outcome

Timeframe: Baseline and 6 months

Population: ITT. Not all subjects in the ITT population completed a YQOL-R.

The Youth Quality of Life-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). The YQOL scores are transformed to a 0-100 scale for easy interpretability. Higher scores indicate better quality of life.

Outcome measures

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=84 Participants Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=33 Participants Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at 6 Months Baseline measure	82.4 Units on a scale Standard Deviation 14.28	80.9 Units on a scale Standard Deviation 14.61
Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at 6 Months 6 months	85.0 Units on a scale Standard Deviation 13.00	84.6 Units on a scale Standard Deviation 10.78
Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at 6 Months Change from baseline at 6 months	1.9 Units on a scale Standard Deviation 9.57	2.7 Units on a scale Standard Deviation 6.23

Adverse Events

Antecedent Methylphenidate Transdermal System (MTS)

Serious events: 3 serious events

Other events: 36 other events

Deaths: 0 deaths

Antecedent Placebo

Serious events: 1 serious events

Other events: 32 other events

Deaths: 0 deaths

Serious adverse events

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=109 participants at risk Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=53 participants at risk Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Nervous system disorders Seizure	1.8% 2/109 Safety population defined as all subjects who received at least one dose of MTS.	0.00% 0/53 Safety population defined as all subjects who received at least one dose of MTS.
Psychiatric disorders Hallucinations	0.92% 1/109 Safety population defined as all subjects who received at least one dose of MTS.	0.00% 0/53 Safety population defined as all subjects who received at least one dose of MTS.
Nervous system disorders Syncope	0.00% 0/109 Safety population defined as all subjects who received at least one dose of MTS.	1.9% 1/53 Safety population defined as all subjects who received at least one dose of MTS.

Other adverse events

Measure	Antecedent Methylphenidate Transdermal System (MTS) n=109 participants at risk Subjects who had previously received MTS in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.	Antecedent Placebo n=53 participants at risk Subjects who had previously received placebo in the antecedent study, SPD485-409. Upon entry into this study (SPD485-410), all subjects received MTS treatment.
Infections and infestations Nasopharyngitis	9.2% 10/109 Safety population defined as all subjects who received at least one dose of MTS.	5.7% 3/53 Safety population defined as all subjects who received at least one dose of MTS.
Infections and infestations Upper respiratory tract infection	10.1% 11/109 Safety population defined as all subjects who received at least one dose of MTS.	11.3% 6/53 Safety population defined as all subjects who received at least one dose of MTS.
Metabolism and nutrition disorders Decreased appetite	11.0% 12/109 Safety population defined as all subjects who received at least one dose of MTS.	24.5% 13/53 Safety population defined as all subjects who received at least one dose of MTS.
Nervous system disorders Headache	10.1% 11/109 Safety population defined as all subjects who received at least one dose of MTS.	15.1% 8/53 Safety population defined as all subjects who received at least one dose of MTS.
Psychiatric disorders Irritability	5.5% 6/109 Safety population defined as all subjects who received at least one dose of MTS.	7.5% 4/53 Safety population defined as all subjects who received at least one dose of MTS.

Additional Information

Timothy Whitaker, MD

Shire Pharmaceutical

Email: twhitaker@shire.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