Attention Deficit Hyperactivity Disorder
Conditions
Keywords
Hyperactivity Attention Deficit Disorder, ADHD, Pediatric Patients, Quillivant, methylphenidate
Brief summary
The objective of this study was to establish that an optimal dose of Quillivant XR oral suspension would result in a significant reduction in signs and symptoms of ADHD compared to placebo treatment in pediatric patients ages 6-12 years with ADHD.
Interventions
DRUGQuillivant Oral Suspension XR
Oral Suspension 25mg/5mL; 20-60 mg/day
DRUGPlacebo
Matching Placebo Oral Suspension 25mg/5mL; 20-60 mg/day
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* Male or female from 6 to 12 years of age at the time of screening, inclusive. * Diagnosis of ADHD by a Psychiatrist, Psychologist, Developmental Pediatrician, or a Pediatrician meeting diagnostic criteria for ADHD (DSM-IV). A Schedule for Affective Disorders and Schizophrenia for School Age Children (K-SADS)16 was administered on all subjects to assist in diagnostic process. * A clinician-administered Clinical Global Impression of Severity (CGI-S) score of 3 or greater. An Attention Deficit Hyperactivity Disorder Rating Scale (ADHD-RS) score at screening or baseline greater than or equal to the 90th percentile normative values for gender and age in at least one of the following categories: the hyperactive-impulsive subscale, inattentive subscale or the total score. * Subject must have been in need of pharmacological treatment for ADHD. * Subjects taking a medication to control ADHD at the time of screening must have been experiencing suboptimal efficacy, a safety or tolerability issue or in need of a long-acting liquid formulation. * For subjects taking any daily medication at screening aside from ADHD medication: parent or legal guardian agreed that there would be no elective changes in subject's medications during the study (10 weeks total).
Exclusion criteria
* Excluded comorbid psychiatric diagnoses: DSM-IV Axis I diagnosis (active) other than ADHD, with the exception of Specific Phobias, Learning Disorders, Motor Skills Disorders, Communication Disorders, Oppositional Defiant Disorder, Elimination Disorders, Sleep Disorders, and Adjustment Disorders. * Clinically significant cognitive impairment as assessed in the clinical judgment of the Investigator. In cases where this was not clear, study staff were permitted to administer a Wechsler Abbreviated Scale of Intelligence (WASI)17 to estimate the intelligence quotient (IQ). Significant cognitive impairment for this protocol was defined as an estimated IQ below 80. * Subjects with chronic medical illnesses including seizure disorder (excluding a history of febrile seizures), severe hypertension, thyroid disease, structural cardiac disorders, serious cardiac conditions, serious arrhythmias, cardiomyopathy, glaucoma, Tourette's Disorder, family history of Tourette's Disorder or tics. * Use of monoamine oxidase inhibitors within 30 days of the screening visit. * Use of any psychotropic medication (except sedative hypnotics prescribed as a sleep aid at a stable dose for at least 30 days prior to screening, at bedtime only). Use of stimulant medication for control of ADHD at screening was permitted if inclusion criterion number 6 was met.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Swanson, Kotin, Agler, M-Flynn, and Pelham Rating Scale (SKAMP)-Combined Scores at Hour 4 Post-Dose | Hour 4 post-dose | The SKAMP scale measures the manifestations of attention deficit hyperactivity disorder (ADHD) using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items (including subscales: attention with items 1-4, deportment with items 5-8, quality of work with items 9-11 and compliance with items 12-13). The SKAMP composite score was obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for a total possible combined score of 0 to 78; where higher score signified worst impairment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | 0.75, 2, 8, 10, 12 hours post-dose | Onset and duration is determined using SKAMP combined rating scale at each post-dose time point. Onset of effect is defined as first assessment time showing statistical significance (i.e. p is less than or equal to \[=\<\] 0.05) between NWP06 and placebo and duration of effect is defined as the as last consecutive time-point at which difference is still statistically significant between NWP06 and placebo. SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP combined score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. |
| SKAMP Attention Subscale Score Over 12 Hours | 0.75, 2, 4, 8, 10, 12 hours post-dose | SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP combined score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. SKAMP attention subscale is reported which evaluates concentration in the classroom and comprises of 4 items, with a total possible score for of 0 to 24; higher score indicates worst impairment. |
| SKAMP Deportment Subscale Score Over 12 Hours | 0.75, 2, 4, 8, 10, 12 hours post-dose | SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP combined score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. SKAMP deportment subscale is reported which assesses behavior in the classroom and comprises of 4 items, with a total possible score for each sub-scale of 0 to 24; higher score indicates worst impairment. |
| Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | 0.75, 2, 4, 8, 10, 12 hours post-dose | The PERMP is a 10-minute written test, on 80 math problems, performed as seatwork in the classroom. At the end of the 10-minute math test , the PERMP score of the number of math problems attempted plus the number of math problems answered correctly in a 10-minute session was used to measure a participant's performance. The total score range from 0-160 with higher scores indicating better performance. |
| SKAMP Combined Scores Over 12 Hours | 0.75, 2, 8, 10, 12 hours post-dose | The SKAMP scale measures the manifestations of attention deficit hyperactivity disorder (ADHD) using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items (including subscales: attention with items 1-4, deportment with items 5-8, quality of work with items 9-11 and compliance with items 12-13). The SKAMP combined score was obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for a total possible combined score of 0 to 78; where higher score signified worst impairment. |
Other
| Measure | Time frame | Description |
|---|---|---|
| SKAMP Quality of Work Subscale Score Over 12 Hours | 0.75, 2, 4, 8, 10, 12 hours post-dose | SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP composite score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP composite score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. SKAMP quality of work subscale is reported which comprises of 3 items, with a total possible score of 0 to 18; higher score indicates worst impairment. |
| SKAMP Compliance Subscale Score Over 12 Hours | 0.75, 2, 4, 8, 10, 12 hours post-dose | SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP composite score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP composite score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. SKAMP compliance subscale is reported which comprises of 2 items, with a total possible score of 0 to 12; higher score indicates worst impairment. |
Countries
United States
Participant flow
Pre-assignment details
The study consisted of an open-label (OL) dose-optimization phase (4 to 6 weeks), and a placebo-controlled, double blind (DB) 2-way crossover phase (1 week each) with no dose adjustments.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Includes all randomized participants who received at least 1 dose of study medication. | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Open Label Phase | Adverse Event | 2 | 0 |
| Open Label Phase | Lack of Efficacy | 1 | 0 |
| Open Label Phase | Lost to Follow-up | 1 | 0 |
| Open Label Phase | Withdrawal by Subject | 2 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 8.8 years STANDARD_DEVIATION 1.69 |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 42 / 45 | 5 / 45 | 11 / 45 |
| serious Total, serious adverse events | 0 / 45 | 0 / 45 | 0 / 45 |
Outcome results
Primary
Swanson, Kotin, Agler, M-Flynn, and Pelham Rating Scale (SKAMP)-Combined Scores at Hour 4 Post-Dose
The SKAMP scale measures the manifestations of attention deficit hyperactivity disorder (ADHD) using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items (including subscales: attention with items 1-4, deportment with items 5-8, quality of work with items 9-11 and compliance with items 12-13). The SKAMP composite score was obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for a total possible combined score of 0 to 78; where higher score signified worst impairment.
Time frame: Hour 4 post-dose
Population: Intent-to-Treat (ITT) analysis set included all randomized participants who received at least 1 dose of study medication (either NWP06 or matching placebo) and had at least 1 post-baseline efficacy assessment. N (number of participants analyzed)= participants evaluable for this measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| NWP06 | Swanson, Kotin, Agler, M-Flynn, and Pelham Rating Scale (SKAMP)-Combined Scores at Hour 4 Post-Dose | 7.1 units on a scale | Standard Deviation 5.64 |
| Placebo | Swanson, Kotin, Agler, M-Flynn, and Pelham Rating Scale (SKAMP)-Combined Scores at Hour 4 Post-Dose | 19.3 units on a scale | Standard Deviation 8.38 |
Comparison: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-14.75, -10.17]ANOVA
Secondary
Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale
Onset and duration is determined using SKAMP combined rating scale at each post-dose time point. Onset of effect is defined as first assessment time showing statistical significance (i.e. p is less than or equal to \[=\<\] 0.05) between NWP06 and placebo and duration of effect is defined as the as last consecutive time-point at which difference is still statistically significant between NWP06 and placebo. SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP combined score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment.
Time frame: 0.75, 2, 8, 10, 12 hours post-dose
Population: Intent-to-Treat (ITT) analysis set included all randomized participants who received at least 1 dose of study medication (either NWP06 or matching placebo) and had at least 1 post-baseline efficacy assessment. N (number of participants analyzed)= participants evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NWP06 | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 2 | 7.2 units on a scale | Standard Deviation 4.73 |
| NWP06 | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 10 | 14.0 units on a scale | Standard Deviation 9.5 |
| NWP06 | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 8 | 10.8 units on a scale | Standard Deviation 8.23 |
| NWP06 | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 12 | 15.1 units on a scale | Standard Deviation 9.38 |
| NWP06 | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 0.75 | 9.5 units on a scale | Standard Deviation 5.77 |
| Placebo | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 12 | 19.8 units on a scale | Standard Deviation 10.91 |
| Placebo | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 0.75 | 15.8 units on a scale | Standard Deviation 7.25 |
| Placebo | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 2 | 16.9 units on a scale | Standard Deviation 7.96 |
| Placebo | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 8 | 20.0 units on a scale | Standard Deviation 9.33 |
| Placebo | Onset and Duration of Clinical Effect Based on SKAMP-Combined Scale | Hour 10 | 17.7 units on a scale | Standard Deviation 9.04 |
Comparison: Hour 0.75: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-8.53, -4.11]ANOVA
Comparison: Hour 2: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-12.04, -7.91]ANOVA
Comparison: Hour 8: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-11.92, -6.75]ANOVA
Comparison: Hour 10: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.001695% CI: [-6.04, -1.54]ANOVA
Comparison: Hour 12: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.001695% CI: [-7.61, -1.94]ANOVA
Secondary
Permanent Product Measure of Performance (PERMP) Score Over 12 Hours
The PERMP is a 10-minute written test, on 80 math problems, performed as seatwork in the classroom. At the end of the 10-minute math test , the PERMP score of the number of math problems attempted plus the number of math problems answered correctly in a 10-minute session was used to measure a participant's performance. The total score range from 0-160 with higher scores indicating better performance.
Time frame: 0.75, 2, 4, 8, 10, 12 hours post-dose
Population: Intent-to-Treat (ITT) analysis set included all randomized participants who received at least 1 dose of study medication (either NWP06 or matching placebo) and had at least 1 post-baseline efficacy assessment. N (number of participants analyzed)= participants evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NWP06 | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 0.75 | 111.1 units on a scale | Standard Deviation 62.4 |
| NWP06 | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 2 | 118.2 units on a scale | Standard Deviation 63.87 |
| NWP06 | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 4 | 119.2 units on a scale | Standard Deviation 64.31 |
| NWP06 | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 8 | 105.2 units on a scale | Standard Deviation 63.94 |
| NWP06 | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 10 | 95.6 units on a scale | Standard Deviation 63.64 |
| NWP06 | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 12 | 94.0 units on a scale | Standard Deviation 61.69 |
| Placebo | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 10 | 82.7 units on a scale | Standard Deviation 57.59 |
| Placebo | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 0.75 | 85.5 units on a scale | Standard Deviation 51.88 |
| Placebo | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 8 | 72.1 units on a scale | Standard Deviation 52.41 |
| Placebo | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 2 | 82.4 units on a scale | Standard Deviation 50.54 |
| Placebo | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 12 | 78.1 units on a scale | Standard Deviation 51.83 |
| Placebo | Permanent Product Measure of Performance (PERMP) Score Over 12 Hours | Hour 4 | 75.5 units on a scale | Standard Deviation 48.62 |
Comparison: Hour 0.75: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [16.26, 34.96]ANOVA
Comparison: Hour 2: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [26.54, 47.66]ANOVA
Comparison: Hour 4: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [30.89, 60.65]ANOVA
Comparison: Hour 8: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [22.14, 48.78]ANOVA
Comparison: Hour 10: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.015595% CI: [3, 26.73]ANOVA
Comparison: Hour 12: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.001995% CI: [8.17, 33.22]ANOVA
Secondary
SKAMP Attention Subscale Score Over 12 Hours
SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP combined score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. SKAMP attention subscale is reported which evaluates concentration in the classroom and comprises of 4 items, with a total possible score for of 0 to 24; higher score indicates worst impairment.
Time frame: 0.75, 2, 4, 8, 10, 12 hours post-dose
Population: Intent-to-Treat (ITT) analysis set included all randomized participants who received at least 1 dose of study medication (either NWP06 or matching placebo) and had at least 1 post-baseline efficacy assessment. N (number of participants analyzed)= participants evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NWP06 | SKAMP Attention Subscale Score Over 12 Hours | Hour 0.75 | 1.3 units on a scale | Standard Deviation 1.64 |
| NWP06 | SKAMP Attention Subscale Score Over 12 Hours | Hour 2 | 1.1 units on a scale | Standard Deviation 1.85 |
| NWP06 | SKAMP Attention Subscale Score Over 12 Hours | Hour 4 | 0.9 units on a scale | Standard Deviation 1.97 |
| NWP06 | SKAMP Attention Subscale Score Over 12 Hours | Hour 8 | 1.2 units on a scale | Standard Deviation 1.96 |
| NWP06 | SKAMP Attention Subscale Score Over 12 Hours | Hour 10 | 2.5 units on a scale | Standard Deviation 2.8 |
| NWP06 | SKAMP Attention Subscale Score Over 12 Hours | Hour 12 | 2.4 units on a scale | Standard Deviation 2.66 |
| Placebo | SKAMP Attention Subscale Score Over 12 Hours | Hour 10 | 3.0 units on a scale | Standard Deviation 3.43 |
| Placebo | SKAMP Attention Subscale Score Over 12 Hours | Hour 0.75 | 2.5 units on a scale | Standard Deviation 2.52 |
| Placebo | SKAMP Attention Subscale Score Over 12 Hours | Hour 8 | 2.7 units on a scale | Standard Deviation 3.58 |
| Placebo | SKAMP Attention Subscale Score Over 12 Hours | Hour 2 | 2.6 units on a scale | Standard Deviation 2.93 |
| Placebo | SKAMP Attention Subscale Score Over 12 Hours | Hour 12 | 3.4 units on a scale | Standard Deviation 3.11 |
| Placebo | SKAMP Attention Subscale Score Over 12 Hours | Hour 4 | 3.1 units on a scale | Standard Deviation 3.49 |
Comparison: Hour 0.75: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.005195% CI: [-1.88, -0.36]ANOVA
Comparison: Hour 2: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-2.23, -0.95]ANOVA
Comparison: Hour 4: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.000195% CI: [-3.37, -1.2]ANOVA
Comparison: Hour 8: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.005595% CI: [-2.52, -0.47]ANOVA
Comparison: Hour 10: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.197795% CI: [-1.38, 0.29]ANOVA
Comparison: Hour 12: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.049195% CI: [-1.76, 0]ANOVA
Secondary
SKAMP Combined Scores Over 12 Hours
The SKAMP scale measures the manifestations of attention deficit hyperactivity disorder (ADHD) using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items (including subscales: attention with items 1-4, deportment with items 5-8, quality of work with items 9-11 and compliance with items 12-13). The SKAMP combined score was obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for a total possible combined score of 0 to 78; where higher score signified worst impairment.
Time frame: 0.75, 2, 8, 10, 12 hours post-dose
Population: Data for combined SKAMP score was collected and reported through the measure of onset and duration of clinical effects as given in outcome measure 2.
Secondary
SKAMP Deportment Subscale Score Over 12 Hours
SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP combined score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP combined score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. SKAMP deportment subscale is reported which assesses behavior in the classroom and comprises of 4 items, with a total possible score for each sub-scale of 0 to 24; higher score indicates worst impairment.
Time frame: 0.75, 2, 4, 8, 10, 12 hours post-dose
Population: Intent-to-Treat (ITT) analysis set included all randomized participants who received at least 1 dose of study medication (either NWP06 or matching placebo) and had at least 1 post-baseline efficacy assessment. N (number of participants analyzed)= participants evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NWP06 | SKAMP Deportment Subscale Score Over 12 Hours | Hour 0.75 | 1.7 units on a scale | Standard Deviation 1.89 |
| NWP06 | SKAMP Deportment Subscale Score Over 12 Hours | Hour 2 | 1.0 units on a scale | Standard Deviation 1.39 |
| NWP06 | SKAMP Deportment Subscale Score Over 12 Hours | Hour 4 | 1.2 units on a scale | Standard Deviation 1.64 |
| NWP06 | SKAMP Deportment Subscale Score Over 12 Hours | Hour 8 | 2.1 units on a scale | Standard Deviation 3.03 |
| NWP06 | SKAMP Deportment Subscale Score Over 12 Hours | Hour 10 | 2.4 units on a scale | Standard Deviation 2.98 |
| NWP06 | SKAMP Deportment Subscale Score Over 12 Hours | Hour 12 | 2.7 units on a scale | Standard Deviation 2.91 |
| Placebo | SKAMP Deportment Subscale Score Over 12 Hours | Hour 10 | 3.7 units on a scale | Standard Deviation 2.57 |
| Placebo | SKAMP Deportment Subscale Score Over 12 Hours | Hour 0.75 | 3.3 units on a scale | Standard Deviation 2.57 |
| Placebo | SKAMP Deportment Subscale Score Over 12 Hours | Hour 8 | 4.5 units on a scale | Standard Deviation 3.21 |
| Placebo | SKAMP Deportment Subscale Score Over 12 Hours | Hour 2 | 3.6 units on a scale | Standard Deviation 3 |
| Placebo | SKAMP Deportment Subscale Score Over 12 Hours | Hour 12 | 4.2 units on a scale | Standard Deviation 3.69 |
| Placebo | SKAMP Deportment Subscale Score Over 12 Hours | Hour 4 | 4.2 units on a scale | Standard Deviation 2.92 |
Comparison: Hour 0.75: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-2.36, -1.02]ANOVA
Comparison: Hour 2: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-3.5, -1.82]ANOVA
Comparison: Hour 4: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-3.77, -2.13]ANOVA
Comparison: Hour 8: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-3.33, -1.66]ANOVA
Comparison: Hour 10: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.003595% CI: [-2.07, -0.44]ANOVA
Comparison: Hour 12: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.010995% CI: [-2.51, -0.35]ANOVA
Other Pre-specified
SKAMP Compliance Subscale Score Over 12 Hours
SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP composite score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP composite score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. SKAMP compliance subscale is reported which comprises of 2 items, with a total possible score of 0 to 12; higher score indicates worst impairment.
Time frame: 0.75, 2, 4, 8, 10, 12 hours post-dose
Population: Intent-to-Treat (ITT) analysis set included all randomized participants who received at least 1 dose of study medication (either NWP06 or matching placebo) and had at least 1 post-baseline efficacy assessment. N (number of participants analyzed)= participants evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NWP06 | SKAMP Compliance Subscale Score Over 12 Hours | Hour 0.75 | 1.9 units on a scale | Standard Deviation 1.96 |
| NWP06 | SKAMP Compliance Subscale Score Over 12 Hours | Hour 4 | 1.3 units on a scale | Standard Deviation 1.77 |
| NWP06 | SKAMP Compliance Subscale Score Over 12 Hours | Hour 8 | 2.1 units on a scale | Standard Deviation 2.46 |
| NWP06 | SKAMP Compliance Subscale Score Over 12 Hours | Hour 10 | 2.7 units on a scale | Standard Deviation 3.01 |
| NWP06 | SKAMP Compliance Subscale Score Over 12 Hours | Hour 12 | 3.5 units on a scale | Standard Deviation 3.16 |
| NWP06 | SKAMP Compliance Subscale Score Over 12 Hours | Hour 2 | 1.2 units on a scale | Standard Deviation 1.51 |
| Placebo | SKAMP Compliance Subscale Score Over 12 Hours | Hour 12 | 4.6 units on a scale | Standard Deviation 3.5 |
| Placebo | SKAMP Compliance Subscale Score Over 12 Hours | Hour 2 | 4.1 units on a scale | Standard Deviation 2.94 |
| Placebo | SKAMP Compliance Subscale Score Over 12 Hours | Hour 10 | 4.4 units on a scale | Standard Deviation 2.94 |
| Placebo | SKAMP Compliance Subscale Score Over 12 Hours | Hour 4 | 4.7 units on a scale | Standard Deviation 2.97 |
| Placebo | SKAMP Compliance Subscale Score Over 12 Hours | Hour 0.75 | 3.5 units on a scale | Standard Deviation 2.67 |
| Placebo | SKAMP Compliance Subscale Score Over 12 Hours | Hour 8 | 4.8 units on a scale | Standard Deviation 3.13 |
Comparison: Hour 0.75: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-2.43, -1]ANOVA
Comparison: Hour 2: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-3.78, -2.1]ANOVA
Comparison: Hour 4: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-4.11, -2.57]ANOVA
Comparison: Hour 8: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-3.64, -1.76]ANOVA
Comparison: Hour 10: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.000695% CI: [-2.4, -0.73]ANOVA
Comparison: Hour 12: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.008795% CI: [-1.94, -0.3]ANOVA
Other Pre-specified
SKAMP Quality of Work Subscale Score Over 12 Hours
SKAMP scale measures the manifestations of ADHD using an independent observer rating of the participant's impairment in classroom observed behaviors. SKAMP composite score is comprised of 13 items \[subscales: attention (1-4 items), deportment (5-8 items), quality of work (9-11 items) and compliance (12-13 items)\]. SKAMP composite score is obtained by summing up each item score where each item is rated on a 7-point impairment scale (0=normal to 6=maximal impairment) for total possible combined score of 0 to 78; where higher score signified worst impairment. SKAMP quality of work subscale is reported which comprises of 3 items, with a total possible score of 0 to 18; higher score indicates worst impairment.
Time frame: 0.75, 2, 4, 8, 10, 12 hours post-dose
Population: Intent-to-Treat (ITT) analysis set included all randomized participants who received at least 1 dose of study medication (either NWP06 or matching placebo) and had at least 1 post-baseline efficacy assessment. N (number of participants analyzed)= participants evaluable for this measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| NWP06 | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 0.75 | 4.6 units on a scale | Standard Deviation 2.38 |
| NWP06 | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 2 | 3.8 units on a scale | Standard Deviation 2.06 |
| NWP06 | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 4 | 3.6 units on a scale | Standard Deviation 2.35 |
| NWP06 | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 8 | 5.5 units on a scale | Standard Deviation 3.06 |
| NWP06 | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 10 | 6.4 units on a scale | Standard Deviation 3.22 |
| NWP06 | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 12 | 6.5 units on a scale | Standard Deviation 3.28 |
| Placebo | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 10 | 6.7 units on a scale | Standard Deviation 2.71 |
| Placebo | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 0.75 | 6.5 units on a scale | Standard Deviation 3.06 |
| Placebo | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 8 | 7.9 units on a scale | Standard Deviation 3.19 |
| Placebo | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 2 | 6.6 units on a scale | Standard Deviation 3.03 |
| Placebo | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 12 | 7.6 units on a scale | Standard Deviation 3.66 |
| Placebo | SKAMP Quality of Work Subscale Score Over 12 Hours | Hour 4 | 7.3 units on a scale | Standard Deviation 3.34 |
Comparison: Hour 0.75: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.001495% CI: [-2.85, -0.74]ANOVA
Comparison: Hour 2: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-3.76, -1.82]ANOVA
Comparison: Hour 4: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: <0.000195% CI: [-5.12, -2.67]ANOVA
Comparison: Hour 8: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.000295% CI: [-3.97, -1.33]ANOVA
Comparison: Hour 10: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.349295% CI: [-1.34, 0.49]ANOVA
Comparison: Hour 12: Treatment comparisons for observed scores were assessed using linear models with sequence (Placebo/NWP06 and NWP06/Placebo), period, and treatment (NWP06 and Placebo) as fixed effects, and participant within sequence as a repeated effect with a compound symmetry correlation structure. A negative point difference indicated a positive effect of NWP06 over Placebo.p-value: 0.010595% CI: [-2.34, -0.33]ANOVA