Quillivant Oral Suspension (Quillivant XR) in the Treatment of Attention Deficit Hyperactivity Disorder (ADHD)

Study Overview
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Brief Summary
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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.

Official Title
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NWP06 in the Treatment of Children With Attention Deficit Hyperactivity Disorder (ADHD)- A Laboratory Classroom Study

Conditions
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Attention Deficit Hyperactivity Disorder

Intervention / Treatment
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* Drug: Quillivant Oral Suspension XR
* Drug: Placebo
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br> | Drug: Quillivant Oral Suspension XR<br>* Oral Suspension 25mg/5mL; 20-60 mg/day<br>* Other names: methylphenidate hydrochloride oral suspension;Drug: Placebo<br>* Matching Placebo Oral Suspension 25mg/5mL; 20-60 mg/day<br>|
| Placebo Comparator: Comparator<br> | Drug: Placebo<br>* Matching placebo was a solution that was identical in taste and appearance to the Active drug that was used in this study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Hour 4 post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0.75, 2, 8, 10, 12 hours post-dose | 
| 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. | 0.75, 2, 4, 8, 10, 12 hours post-dose | 
| 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. | 0.75, 2, 4, 8, 10, 12 hours post-dose | 
| 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. | 0.75, 2, 4, 8, 10, 12 hours post-dose | 
| 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. | 0.75, 2, 8, 10, 12 hours post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperactivity Attention Deficit Disorder, ADHD, Pediatric Patients, Quillivant, methylphenidate