ADHD
Conditions
Brief summary
To evaluate the long-term, safety of Methylphenidate Transdermal System (MTS) in aged 13-17 years diagnosed withADHD
Detailed description
To evaluate the long-term, safety of Methylphenidate Transdermal System (MTS) in the symptomatic treatment of adolescents aged 13-17 years diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD) by Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) criteria. The evaluation of safety will be based on treatment-emergent adverse events (TEAEs), laboratory tests, vital signs, physical examinations, electrocardiograms (ECGs), and skin tolerability to MTS based on the dermal response score (DRS).
Interventions
One of 4 doses of the MTS transdermal patch over the same duration of wear for approximately 6 months
Sponsors
Noven Therapeutics
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
13 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
To be eligible for inclusion, each subject must fulfill each of the following criteria at the Entry visit: * The subject participated in the antecedent SPD485-409 study, and a) completed all required study visits (Baseline through Visit 9) OR b) completed the 5 week Dose Optimization period without achieving an acceptable condition as defined by the antecedent SPD485-409 study. * Subject has blood pressure measurements within the 95th percentile for age, gender, and height at Entry. * Subject's ECG results are within the normal range or not clinically significant at Entry as judged by the Investigator in conjunction with the central reader. * Females must have a negative urine pregnancy test at Entry and agree to use acceptable contraceptives throughout the study period and for 30 days the last dose of IP. * Subject and parent of legally authorized representative (LAR) are able, willing and likely to fully comply with study procedures and restrictions. * Written, signed and dated informed consent to participate in the study must be given by the subject's parent or LAR, in accordance with the International Conference on Harmonisation (ICH), Good Clinical Practices (GCP) Guideline E6 and applicable regulations, before completing any study-related procedures. * There must be documentation of the subject's assent to participate in the study indicating that the subject is aware of the investigational nature of the study and the required procedures and restrictions. Failure to object is not to be considered assent.
Exclusion criteria
Subjects will be excluded from the study if any of the following criteria are met at Entry: * Subject was discontinued from SPD485-409 due to a protocol violation, non-compliance, AE, or a serious adverse event (SAE). * Subject has a concurrent chronic or acute illness (such as severe allergic rhinitis or an infectious process requiring antibiotics), disability, or other condition that might confound the results of safety assessments administered in the study or that might increase risk to the subject. Similarly, the subject will be excluded if he or she has any additional condition(s) that in the Investigator's opinion would prohibit the subject from completing the study or would not be in the best interest of the subject. This would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol. Mild, stable asthma is not exclusionary. * Subject is taking any medication that is excluded. * Female subject who is pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Dermal Reactions | 6 months | 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. |
| Diastolic Blood Pressure | Baseline and 6 months | — |
| Pulse Rate | Baseline and 6 months | — |
| Electrocardiogram Results (QTcF Interval) | Baseline and 6 months | 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. |
| Post Sleep Questionnaire (PSQ) Quality of Sleep | 6 months | 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. |
| Weight | Baseline and 6 months | — |
| Systolic Blood Pressure | Baseline and 6 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) at 6 Months | Baseline and 6 months | 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. |
| Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 6 months | 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. |
| Number of Participants With Improvement on Parent Global Assessment (PGA) Scores. | 6 months | 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. |
| Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at 6 Months | Baseline and 6 months | 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. |
| Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Scores at 6 Months | Baseline and 6 months | 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. |
Countries
United States
Participant flow
Recruitment details
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.
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 110 |
| 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. | 53 |
| Total | 163 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Maintenance Period | Adverse Event | 6 | 6 |
| Maintenance Period | Application site reaction | 1 | 0 |
| Maintenance Period | Lack of Efficacy | 4 | 1 |
| Maintenance Period | Lost to Follow-up | 12 | 7 |
| Maintenance Period | Noncompliant with study medication | 5 | 0 |
| Maintenance Period | Protocol Violation | 2 | 1 |
| Maintenance Period | Went into rehabilitation | 1 | 0 |
| Maintenance Period | Withdrawal by Subject | 14 | 13 |
| Maintenance Period | Would not wear patch | 1 | 0 |
| Optimization Period | Enrolled in error | 1 | 0 |
Baseline characteristics
| Characteristic | Antecedent Placebo | Antecedent Methylphenidate Transdermal System (MTS) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 53 Participants | 110 Participants | 163 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 | 14.5 years STANDARD_DEVIATION 1.37 | 14.5 years STANDARD_DEVIATION 1.18 | 14.5 years STANDARD_DEVIATION 1.24 |
| Region of Enrollment United States | 53 participants | 110 participants | 163 participants |
| Sex: Female, Male Female | 14 Participants | 27 Participants | 41 Participants |
| Sex: Female, Male Male | 39 Participants | 83 Participants | 122 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 36 / 109 | 32 / 53 |
| serious Total, serious adverse events | 3 / 109 | 1 / 53 |
Outcome results
Primary
Dermal Reactions
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.
Time frame: 6 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | 6 (Vesicular eruption) | 0 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | 0 (No evidence of irritation) | 23 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | 1 (Minimal erythema) | 42 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | 2 (Definite erythema) | 82 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | 3 (Erythema and papules) | 6 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | 4 (Definite edema) | 0 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | 5 (Erythema, edema, and papules) | 4 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | 7 (Strong reaction beyond test site) | 0 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Dermal Reactions | No dermal evaluation | 5 Participants |
Primary
Diastolic Blood Pressure
Time frame: Baseline and 6 months
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Diastolic Blood Pressure | Baseline measure | 69.4 mmHg | Standard Deviation 7.42 |
| Antecedent Methylphenidate Transdermal System (MTS) | Diastolic Blood Pressure | 6 months | 67.9 mmHg | Standard Deviation 7.79 |
| Antecedent Placebo | Diastolic Blood Pressure | Baseline measure | 67.2 mmHg | Standard Deviation 7.69 |
| Antecedent Placebo | Diastolic Blood Pressure | 6 months | 68.9 mmHg | Standard Deviation 8.28 |
Primary
Electrocardiogram Results (QTcF Interval)
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.
Time frame: Baseline and 6 months
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Electrocardiogram Results (QTcF Interval) | Baseline measure | 391.8 msec | Standard Deviation 20.76 |
| Antecedent Methylphenidate Transdermal System (MTS) | Electrocardiogram Results (QTcF Interval) | 6 months | 395.3 msec | Standard Deviation 21.22 |
| Antecedent Placebo | Electrocardiogram Results (QTcF Interval) | Baseline measure | 393.2 msec | Standard Deviation 17.85 |
| Antecedent Placebo | Electrocardiogram Results (QTcF Interval) | 6 months | 393.5 msec | Standard Deviation 21.53 |
Primary
Post Sleep Questionnaire (PSQ) Quality of Sleep
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.
Time frame: 6 months
Population: Safety Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Post Sleep Questionnaire (PSQ) Quality of Sleep | Poor | 6 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Post Sleep Questionnaire (PSQ) Quality of Sleep | Good | 27 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Post Sleep Questionnaire (PSQ) Quality of Sleep | Average | 34 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Post Sleep Questionnaire (PSQ) Quality of Sleep | Very Good | 23 Participants |
| Antecedent Methylphenidate Transdermal System (MTS) | Post Sleep Questionnaire (PSQ) Quality of Sleep | Very poor | 1 Participants |
| Antecedent Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep | Very Good | 9 Participants |
| Antecedent Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep | Very poor | 1 Participants |
| Antecedent Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep | Poor | 3 Participants |
| Antecedent Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep | Average | 10 Participants |
| Antecedent Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep | Good | 15 Participants |
Primary
Pulse Rate
Time frame: Baseline and 6 months
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Pulse Rate | Baseline measure | 80.4 beats per minute | Standard Deviation 11.34 |
| Antecedent Methylphenidate Transdermal System (MTS) | Pulse Rate | 6 months | 81.7 beats per minute | Standard Deviation 11.6 |
| Antecedent Placebo | Pulse Rate | Baseline measure | 74.3 beats per minute | Standard Deviation 9.73 |
| Antecedent Placebo | Pulse Rate | 6 months | 78.9 beats per minute | Standard Deviation 12.27 |
Primary
Systolic Blood Pressure
Time frame: Baseline and 6 months
Population: Safety population defined as all subjects that received at least one dose of MTS.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Systolic Blood Pressure | Baseline measure | 113.4 mmHg | Standard Deviation 9.59 |
| Antecedent Methylphenidate Transdermal System (MTS) | Systolic Blood Pressure | 6 months | 115.3 mmHg | Standard Deviation 9.91 |
| Antecedent Placebo | Systolic Blood Pressure | Baseline measure | 113.0 mmHg | Standard Deviation 11.2 |
| Antecedent Placebo | Systolic Blood Pressure | 6 months | 115.9 mmHg | Standard Deviation 14.82 |
Primary
Weight
Time frame: Baseline and 6 months
Population: Safety population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Weight | Baseline measure | 127.05 lb | Standard Deviation 24.003 |
| Antecedent Methylphenidate Transdermal System (MTS) | Weight | 6 months | 134.55 lb | Standard Deviation 25.575 |
| Antecedent Placebo | Weight | Baseline measure | 131.95 lb | Standard Deviation 29.862 |
| Antecedent Placebo | Weight | 6 months | 124.78 lb | Standard Deviation 29.083 |
Secondary
Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Scores at 6 Months
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | 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 |
| Antecedent Methylphenidate Transdermal System (MTS) | 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 |
| Antecedent Methylphenidate Transdermal System (MTS) | 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 11.8 |
| Antecedent Placebo | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Scores at 6 Months | Baseline measure | 27.4 Units on a scale | Standard Deviation 12.91 |
| Antecedent Placebo | Change From Baseline in Attention Deficit Hyperactivity Disorder Rating Scale-fourth Edition (ADHD-RS-IV) Scores at 6 Months | 6 months | 14.5 Units on a scale | Standard Deviation 9.53 |
| Antecedent Placebo | 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 | -12.9 Units on a scale | Standard Deviation 15.2 |
p-value: 0.028t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) at 6 Months
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.
Time frame: Baseline and 6 months
Population: ITT
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | 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 |
| Antecedent Methylphenidate Transdermal System (MTS) | 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 |
| Antecedent Methylphenidate Transdermal System (MTS) | 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 |
| Antecedent Placebo | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) at 6 Months | Baseline measure | 42.3 Units on a scale | Standard Deviation 16.94 |
| Antecedent Placebo | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) at 6 Months | 6 months | 24.6 Units on a scale | Standard Deviation 12.92 |
| Antecedent Placebo | Change From Baseline in Conner's Parent Rating Scale-revised Short Version (CPRS-R) at 6 Months | Change from baseline at 6 months | -17.7 Units on a scale | Standard Deviation 20.1 |
p-value: 0.027t-test, 2 sided
p-value: <0.001t-test, 2 sided
Secondary
Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at 6 Months
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.
Time frame: Baseline and 6 months
Population: ITT. Not all subjects in the ITT population completed a YQOL-R.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | 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 |
| Antecedent Methylphenidate Transdermal System (MTS) | 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 |
| Antecedent Methylphenidate Transdermal System (MTS) | 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 |
| Antecedent Placebo | Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at 6 Months | Baseline measure | 80.9 Units on a scale | Standard Deviation 14.61 |
| Antecedent Placebo | Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at 6 Months | 6 months | 84.6 Units on a scale | Standard Deviation 10.78 |
| Antecedent Placebo | Change From Baseline in Youth Quality of Life-research Version (YQOL-R) Total Score at 6 Months | Change from baseline at 6 months | 2.7 Units on a scale | Standard Deviation 6.23 |
p-value: 0.071t-test, 2 sided
p-value: 0.017t-test, 2 sided
Secondary
Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores
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.
Time frame: 6 months
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 81 Participants |
| Antecedent Placebo | Number of Participants With Improvement on Clinical Global Impression-Improvement (CGI-I) Scores | 39 Participants |
Secondary
Number of Participants With Improvement on Parent Global Assessment (PGA) Scores.
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.
Time frame: 6 months
Population: ITT
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Antecedent Methylphenidate Transdermal System (MTS) | Number of Participants With Improvement on Parent Global Assessment (PGA) Scores. | 69 Participants |
| Antecedent Placebo | Number of Participants With Improvement on Parent Global Assessment (PGA) Scores. | 31 Participants |