Attention-Deficit/Hyperactivity Disorder
Conditions
Keywords
ADHD
Brief summary
The primary purpose is to assess the efficacy of once daily dosing with optimized SPD503 (1, 2, 3 and 4mg/day), dosed either in the morning or evening, compared to placebo, in children with ADHD as measured by change from baseline score at endpoint on the ADHD-RS-IV.
Interventions
dosed in AM
DRUGplacebo
dosed in the AM or PM
Dosed in the PM
Sponsors
Shire
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* 6-12 years old * ADHD diagnosis * ADHD-RS-IV minimum score of 28 * CGI-S score \> or = 4
Exclusion criteria
* Current, controlled or uncontrolled, comorbid psychiatric diagnosis * Condition or illness which represent inappropriate risk to subject * Known history or presence of structural cardiac abnormalities, serious heart rhythm abnormalities, syncope, cardiac conduction problems, exercise-related cardiac events, or clinically significant bradycardia; orthostatic hypotension or controlled or uncontrolled hypertension * Use of prohibited medication that have CNS effects or affect cognitive performance * History of alcohol or substance abuse within 6 months * Current use of medication that affect BP or heart rate * Significantly overweight * Weight of less than 55 lbs * Known allergy to SPD503 * Abnormal urine drug and alcohol screen
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Attention-Deficit/Hyperactivity Disorder-Rating Scale-IV (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF) | Baseline and up to 8 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 8 - LOCF | Baseline and up to 8 weeks | The Pediatric Daytime Sleepiness Scale (PDSS) is an 8 question questionnaire scored on a scale from 0 (never) to 4 (always). Total scores range from 0 to 32, with increasing score reflecting greater sleepiness. |
| Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Baseline and up to 8 weeks | CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill) |
| Improvement on Clinical Global Impression-Improvement (CGI-I) Scale at Week 8 - LOCF | up to 8 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. |
| Change From Baseline in Conner's Parent Rating Scale - Revised Short Version (CPRS-R:S) Score at Week 8 - LOCF | Baseline and up to 8 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) 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. |
| Change From Baseline in the Bedtime Resistance Subscale of Child's Sleep Habits Questionnaire (CSHQ) at Week 8 - LOCF | Baseline and up to 8 weeks | The bedtime resistance subscale of CSHQ consists of 6 items scored on a scale from 1 (never/rarely) to 3 (Usually). A higher score reflects more disturbed sleep behavior. |
| Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | up to 8 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. |
| Change From Baseline in Health Utilities Index-2/3 (HUI 2/3) Scores at Week 8 - LOCF | Baseline and up to 8 weeks | HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status. |
| Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Baseline and up to 8 weeks | — |
| Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Baseline and up to 8 weeks | — |
| Change From Baseline in Pulse Rate at Week 8 - LOCF | Baseline and up to 8 weeks | — |
| Change From Baseline in Oral Temperature at Week 8 - LOCF | Baseline and up to 8 weeks | — |
| Change From Baseline in Height at Week 8 - LOCF | Baseline and up to 8 weeks | — |
| Change From Baseline in Weight at Week 8 - LOCF | Baseline and up to 8 weeks | — |
| Change From Baseline in Mean Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 8 - LOCF | Baseline and up to 8 weeks | The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Mean scores range from 0 to 3. |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Dosed once daily in the morning (upon awakening) and once daily in the evening (7:00 PM) | 112 |
| SPD503 AM SPD503 dosed once daily at either 1, 2, 3 or 4 mg in the morning (upon awakening) and placebo dosed once daily in the PM (7:00 PM) | 107 |
| SPD503 PM Placebo dosed once daily in the AM (upon awakening) and SPD503 dosed once daily at either 1, 2, 3 or 4 mg in the PM (7:00 PM) | 114 |
| Total | 333 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 8 | 8 |
| Overall Study | Lack of Efficacy | 20 | 6 | 3 |
| Overall Study | Lost to Follow-up | 8 | 5 | 4 |
| Overall Study | Met exclusion criteria | 1 | 0 | 0 |
| Overall Study | non-compliance | 0 | 2 | 3 |
| Overall Study | Protocol Violation | 1 | 3 | 0 |
| Overall Study | Suicidal ideation | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 6 | 9 | 5 |
| Overall Study | Work schedule | 0 | 0 | 2 |
| Overall Study | Wrong medication dispensed | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo | SPD503 AM | SPD503 PM | Total |
|---|---|---|---|---|
| Age, Continuous | 8.9 years STANDARD_DEVIATION 1.78 | 9.1 years STANDARD_DEVIATION 1.77 | 9.3 years STANDARD_DEVIATION 1.76 | 9.1 years STANDARD_DEVIATION 1.77 |
| Age, Customized 6-12 years | 112 Participants | 107 Participants | 114 Participants | 333 Participants |
| Region of Enrollment Canada | 2 Participants | 3 Participants | 4 Participants | 9 Participants |
| Region of Enrollment United States | 110 Participants | 104 Participants | 110 Participants | 324 Participants |
| Sex: Female, Male Female | 27 Participants | 35 Participants | 36 Participants | 98 Participants |
| Sex: Female, Male Male | 85 Participants | 72 Participants | 78 Participants | 235 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 64 / 112 | 85 / 107 | 95 / 114 | 180 / 221 |
| serious Total, serious adverse events | 0 / 112 | 1 / 107 | 2 / 114 | 3 / 221 |
Outcome results
Primary
Change From Baseline in Attention-Deficit/Hyperactivity Disorder-Rating Scale-IV (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF)
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 up to 8 weeks
Population: Full Analysis Set (FAS) defined as all subjects who had taken at least 1 dose of investigational product during the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Attention-Deficit/Hyperactivity Disorder-Rating Scale-IV (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF) | -10.6 Units on a scale | Standard Error 1.2 |
| SPD503 AM | Change From Baseline in Attention-Deficit/Hyperactivity Disorder-Rating Scale-IV (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF) | -20.0 Units on a scale | Standard Error 1.23 |
| SPD503 PM | Change From Baseline in Attention-Deficit/Hyperactivity Disorder-Rating Scale-IV (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF) | -20.4 Units on a scale | Standard Error 1.19 |
| All-Active | Change From Baseline in Attention-Deficit/Hyperactivity Disorder-Rating Scale-IV (ADHD-RS-IV) Total Score at Week 8 - Last Observation Carried Forward (LOCF) | -20.2 Units on a scale | Standard Error 0.86 |
Comparison: Study designed to detect an effect size of 0.4 with 90% at the 0.05 significance level.p-value: <0.001ANCOVA
Comparison: Study designed to detect an effect size of 0.4 with 90% at the 0.05 significance level.p-value: <0.001ANCOVA
Comparison: Study designed to detect an effect size of 0.4 with 90% at the 0.05 significance level.p-value: <0.001ANCOVA
Secondary
Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF
CGI-S assesses the severity of the subject's condition on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill)
Time frame: Baseline and up to 8 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Normal, not at all ill | 4.5 Percent of Participants |
| Placebo | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Severely ill | 7.3 Percent of Participants |
| Placebo | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Markedly ill | 30.0 Percent of Participants |
| Placebo | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Borderline mentally ill | 8.2 Percent of Participants |
| Placebo | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Among the most extremely ill | 0.0 Percent of Participants |
| Placebo | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Mildly ill | 15.5 Percent of Participants |
| Placebo | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Moderately ill | 34.5 Percent of Participants |
| SPD503 AM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Severely ill | 1.0 Percent of Participants |
| SPD503 AM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Moderately ill | 22.1 Percent of Participants |
| SPD503 AM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Mildly ill | 32.7 Percent of Participants |
| SPD503 AM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Markedly ill | 11.5 Percent of Participants |
| SPD503 AM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Among the most extremely ill | 1.0 Percent of Participants |
| SPD503 AM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Borderline mentally ill | 20.2 Percent of Participants |
| SPD503 AM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Normal, not at all ill | 11.5 Percent of Participants |
| SPD503 PM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Moderately ill | 22.3 Percent of Participants |
| SPD503 PM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Normal, not at all ill | 16.1 Percent of Participants |
| SPD503 PM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Borderline mentally ill | 20.5 Percent of Participants |
| SPD503 PM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Mildly ill | 27.7 Percent of Participants |
| SPD503 PM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Markedly ill | 10.7 Percent of Participants |
| SPD503 PM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Severely ill | 2.7 Percent of Participants |
| SPD503 PM | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Among the most extremely ill | 0.0 Percent of Participants |
| All-Active | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Mildly ill | 30.1 Percent of Participants |
| All-Active | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Among the most extremely ill | 0.5 Percent of Participants |
| All-Active | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Severely ill | 1.9 Percent of Participants |
| All-Active | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Borderline mentally ill | 20.4 Percent of Participants |
| All-Active | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Normal, not at all ill | 13.9 Percent of Participants |
| All-Active | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Markedly ill | 11.1 Percent of Participants |
| All-Active | Assessment of Clinical Global Impression-Severity of Illness (CGI-S) at Week 8 - LOCF | Moderately ill | 22.2 Percent of Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Change From Baseline in Conner's Parent Rating Scale - Revised Short Version (CPRS-R:S) Score at Week 8 - LOCF
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 up to 8 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Conner's Parent Rating Scale - Revised Short Version (CPRS-R:S) Score at Week 8 - LOCF | -10.4 Units on a scale | Standard Error 1.89 |
| SPD503 AM | Change From Baseline in Conner's Parent Rating Scale - Revised Short Version (CPRS-R:S) Score at Week 8 - LOCF | -22.9 Units on a scale | Standard Error 1.88 |
| SPD503 PM | Change From Baseline in Conner's Parent Rating Scale - Revised Short Version (CPRS-R:S) Score at Week 8 - LOCF | -21.2 Units on a scale | Standard Error 1.84 |
| All-Active | Change From Baseline in Conner's Parent Rating Scale - Revised Short Version (CPRS-R:S) Score at Week 8 - LOCF | -22.0 Units on a scale | Standard Error 1.31 |
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
p-value: <0.001ANCOVA
Secondary
Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF
Time frame: Baseline and up to 8 weeks
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Supine | -0.3 mmHg | Standard Deviation 7.1 |
| Placebo | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Orthostatic | 0.4 mmHg | Standard Deviation 6.31 |
| Placebo | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Standing | 0.2 mmHg | Standard Deviation 7.74 |
| SPD503 AM | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Supine | -0.8 mmHg | Standard Deviation 7.98 |
| SPD503 AM | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Orthostatic | -1.4 mmHg | Standard Deviation 9.35 |
| SPD503 AM | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Standing | -2.2 mmHg | Standard Deviation 8.04 |
| SPD503 PM | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Standing | -2.5 mmHg | Standard Deviation 9.91 |
| SPD503 PM | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Supine | -2.1 mmHg | Standard Deviation 8.71 |
| SPD503 PM | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Orthostatic | -0.4 mmHg | Standard Deviation 8.94 |
| All-Active | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Supine | -1.5 mmHg | Standard Deviation 8.37 |
| All-Active | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Orthostatic | -0.9 mmHg | Standard Deviation 9.13 |
| All-Active | Change From Baseline in Diastolic Blood Pressure at Week 8 - LOCF | Standing | -2.4 mmHg | Standard Deviation 9.04 |
Secondary
Change From Baseline in Health Utilities Index-2/3 (HUI 2/3) Scores at Week 8 - LOCF
HUI is used to describe health status and to obtain utility scores by collecting data using one or more questionnaires in formats selected to match the specific study design criteria. Scoring ranges from 0.00 (dead) to 1.00 (perfect health). Higher scores represent better health status.
Time frame: Baseline and up to 8 weeks
Population: FAS
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Health Utilities Index-2/3 (HUI 2/3) Scores at Week 8 - LOCF | 0.043 Units on a scale | Standard Deviation 0.1159 |
| SPD503 AM | Change From Baseline in Health Utilities Index-2/3 (HUI 2/3) Scores at Week 8 - LOCF | 0.056 Units on a scale | Standard Deviation 0.1166 |
| SPD503 PM | Change From Baseline in Health Utilities Index-2/3 (HUI 2/3) Scores at Week 8 - LOCF | 0.063 Units on a scale | Standard Deviation 0.11 |
| All-Active | Change From Baseline in Health Utilities Index-2/3 (HUI 2/3) Scores at Week 8 - LOCF | 0.060 Units on a scale | Standard Deviation 0.1131 |
Secondary
Change From Baseline in Height at Week 8 - LOCF
Time frame: Baseline and up to 8 weeks
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Height at Week 8 - LOCF | 0.28 inches | Standard Deviation 0.412 |
| SPD503 AM | Change From Baseline in Height at Week 8 - LOCF | 0.39 inches | Standard Deviation 0.602 |
| SPD503 PM | Change From Baseline in Height at Week 8 - LOCF | 0.43 inches | Standard Deviation 0.459 |
| All-Active | Change From Baseline in Height at Week 8 - LOCF | 0.41 inches | Standard Deviation 0.536 |
Secondary
Change From Baseline in Mean Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 8 - LOCF
The WFIRS-P is a 50-item scale with each item scored from 0 (never/not at all) to 3 (very often/very much). Higher scores indicate greater functional impairment. Mean scores range from 0 to 3.
Time frame: Baseline and up to 8 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Mean Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 8 - LOCF | -0.20 Units on a scale | Standard Error 0.038 |
| SPD503 AM | Change From Baseline in Mean Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 8 - LOCF | -0.35 Units on a scale | Standard Error 0.037 |
| SPD503 PM | Change From Baseline in Mean Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 8 - LOCF | -0.37 Units on a scale | Standard Error 0.037 |
| All-Active | Change From Baseline in Mean Weiss Functional Impairment Rating Scale - Parent Report (WFIRS-P) Global Score at Week 8 - LOCF | -0.36 Units on a scale | Standard Error 0.026 |
p-value: <0.001ANCOVA
p-value: 0.004ANCOVA
p-value: 0.001ANCOVA
Secondary
Change From Baseline in Oral Temperature at Week 8 - LOCF
Time frame: Baseline and up to 8 weeks
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Oral Temperature at Week 8 - LOCF | 0.06 º F | Standard Deviation 0.779 |
| SPD503 AM | Change From Baseline in Oral Temperature at Week 8 - LOCF | -0.12 º F | Standard Deviation 0.659 |
| SPD503 PM | Change From Baseline in Oral Temperature at Week 8 - LOCF | -0.09 º F | Standard Deviation 0.758 |
| All-Active | Change From Baseline in Oral Temperature at Week 8 - LOCF | -0.10 º F | Standard Deviation 0.71 |
Secondary
Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 8 - LOCF
The Pediatric Daytime Sleepiness Scale (PDSS) is an 8 question questionnaire scored on a scale from 0 (never) to 4 (always). Total scores range from 0 to 32, with increasing score reflecting greater sleepiness.
Time frame: Baseline and up to 8 weeks
Population: Safety Population defined as all subjects who had taken at least 1 dose of investigational product during the study.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 8 - LOCF | -3.1 Units on a scale | Standard Error 0.53 |
| SPD503 AM | Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 8 - LOCF | -2.7 Units on a scale | Standard Error 0.55 |
| SPD503 PM | Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 8 - LOCF | -1.4 Units on a scale | Standard Error 0.53 |
| All-Active | Change From Baseline in Pediatric Daytime Sleepiness Scale (PDSS) Total Score at Week 8 - LOCF | -2.0 Units on a scale | Standard Error 0.38 |
p-value: 0.099ANCOVA
p-value: 0.596ANCOVA
p-value: 0.023ANCOVA
Secondary
Change From Baseline in Pulse Rate at Week 8 - LOCF
Time frame: Baseline and up to 8 weeks
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Pulse Rate at Week 8 - LOCF | Supine | 1.0 beats per minute | Standard Deviation 11.93 |
| Placebo | Change From Baseline in Pulse Rate at Week 8 - LOCF | Standing | 0.9 beats per minute | Standard Deviation 12.02 |
| SPD503 AM | Change From Baseline in Pulse Rate at Week 8 - LOCF | Standing | -1.9 beats per minute | Standard Deviation 14.84 |
| SPD503 AM | Change From Baseline in Pulse Rate at Week 8 - LOCF | Supine | -3.7 beats per minute | Standard Deviation 12.35 |
| SPD503 PM | Change From Baseline in Pulse Rate at Week 8 - LOCF | Standing | -2.3 beats per minute | Standard Deviation 11.41 |
| SPD503 PM | Change From Baseline in Pulse Rate at Week 8 - LOCF | Supine | -3.8 beats per minute | Standard Deviation 11.95 |
| All-Active | Change From Baseline in Pulse Rate at Week 8 - LOCF | Standing | -2.1 beats per minute | Standard Deviation 13.15 |
| All-Active | Change From Baseline in Pulse Rate at Week 8 - LOCF | Supine | -3.8 beats per minute | Standard Deviation 12.12 |
Secondary
Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF
Time frame: Baseline and up to 8 weeks
Population: Safety Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Supine | -0.5 mmHg | Standard Deviation 9.39 |
| Placebo | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Orthostatic | -0.9 mmHg | Standard Deviation 9.14 |
| Placebo | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Standing | -1.4 mmHg | Standard Deviation 9.08 |
| SPD503 AM | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Supine | -1.6 mmHg | Standard Deviation 9.86 |
| SPD503 AM | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Orthostatic | -1.7 mmHg | Standard Deviation 9.89 |
| SPD503 AM | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Standing | -3.3 mmHg | Standard Deviation 11.23 |
| SPD503 PM | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Standing | -2.7 mmHg | Standard Deviation 11.23 |
| SPD503 PM | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Supine | -2.1 mmHg | Standard Deviation 10.26 |
| SPD503 PM | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Orthostatic | -0.6 mmHg | Standard Deviation 8.93 |
| All-Active | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Supine | -1.9 mmHg | Standard Deviation 10.05 |
| All-Active | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Orthostatic | -1.1 mmHg | Standard Deviation 9.4 |
| All-Active | Change From Baseline in Systolic Blood Pressure at Week 8 - LOCF | Standing | -3.0 mmHg | Standard Deviation 11.2 |
Secondary
Change From Baseline in the Bedtime Resistance Subscale of Child's Sleep Habits Questionnaire (CSHQ) at Week 8 - LOCF
The bedtime resistance subscale of CSHQ consists of 6 items scored on a scale from 1 (never/rarely) to 3 (Usually). A higher score reflects more disturbed sleep behavior.
Time frame: Baseline and up to 8 weeks
Population: FAS
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in the Bedtime Resistance Subscale of Child's Sleep Habits Questionnaire (CSHQ) at Week 8 - LOCF | -0.7 Units on a scale | Standard Error 0.18 |
| SPD503 AM | Change From Baseline in the Bedtime Resistance Subscale of Child's Sleep Habits Questionnaire (CSHQ) at Week 8 - LOCF | -0.5 Units on a scale | Standard Error 0.18 |
| SPD503 PM | Change From Baseline in the Bedtime Resistance Subscale of Child's Sleep Habits Questionnaire (CSHQ) at Week 8 - LOCF | -1.0 Units on a scale | Standard Error 0.18 |
| All-Active | Change From Baseline in the Bedtime Resistance Subscale of Child's Sleep Habits Questionnaire (CSHQ) at Week 8 - LOCF | -0.8 Units on a scale | Standard Error 0.13 |
p-value: 0.712ANCOVA
p-value: 0.531ANCOVA
p-value: 0.226ANCOVA
Secondary
Change From Baseline in Weight at Week 8 - LOCF
Time frame: Baseline and up to 8 weeks
Population: Safety Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Weight at Week 8 - LOCF | 2.15 pounds | Standard Deviation 2.774 |
| SPD503 AM | Change From Baseline in Weight at Week 8 - LOCF | 2.37 pounds | Standard Deviation 2.684 |
| SPD503 PM | Change From Baseline in Weight at Week 8 - LOCF | 2.64 pounds | Standard Deviation 3.006 |
| All-Active | Change From Baseline in Weight at Week 8 - LOCF | 2.50 pounds | Standard Deviation 2.843 |
Secondary
Improvement on Clinical Global Impression-Improvement (CGI-I) Scale at Week 8 - LOCF
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.
Time frame: up to 8 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Improvement on Clinical Global Impression-Improvement (CGI-I) Scale at Week 8 - LOCF | 31.8 Percent of Participants |
| SPD503 AM | Improvement on Clinical Global Impression-Improvement (CGI-I) Scale at Week 8 - LOCF | 66.3 Percent of Participants |
| SPD503 PM | Improvement on Clinical Global Impression-Improvement (CGI-I) Scale at Week 8 - LOCF | 67.0 Percent of Participants |
| All-Active | Improvement on Clinical Global Impression-Improvement (CGI-I) Scale at Week 8 - LOCF | 66.7 Percent of Participants |
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
p-value: <0.001Cochran-Mantel-Haenszel
Secondary
Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF
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: up to 8 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Good | 35.5 Percent of Participants |
| Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Poor | 6.4 Percent of Participants |
| Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Very good | 26.4 Percent of Participants |
| Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Average | 29.1 Percent of Participants |
| Placebo | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Very poor | 2.7 Percent of Participants |
| SPD503 AM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Average | 26.0 Percent of Participants |
| SPD503 AM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Good | 42.3 Percent of Participants |
| SPD503 AM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Very good | 25.0 Percent of Participants |
| SPD503 AM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Poor | 5.8 Percent of Participants |
| SPD503 AM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Very poor | 1.0 Percent of Participants |
| SPD503 PM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Average | 27.7 Percent of Participants |
| SPD503 PM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Very poor | 0.0 Percent of Participants |
| SPD503 PM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Poor | 7.1 Percent of Participants |
| SPD503 PM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Good | 50.9 Percent of Participants |
| SPD503 PM | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Very good | 14.3 Percent of Participants |
| All-Active | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Good | 46.8 Percent of Participants |
| All-Active | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Poor | 6.5 Percent of Participants |
| All-Active | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Very poor | 0.5 Percent of Participants |
| All-Active | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Average | 26.9 Percent of Participants |
| All-Active | Post Sleep Questionnaire (PSQ) Quality of Sleep at Week 8 - LOCF | Very good | 19.4 Percent of Participants |
p-value: 0.859Cochran-Mantel-Haenszel
p-value: 0.527Cochran-Mantel-Haenszel
p-value: 0.739Cochran-Mantel-Haenszel