KP415 Classroom Study in Children (6-12 Years of Age) With ADHD

Study Overview
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Brief Summary
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The study is a multicenter, dose-optimized, double-blind, randomized, placebo-controlled, parallel efficacy laboratory classroom study with KP415 in children with Attention-Deficit/Hyperactivity Disorder (ADHD).

Detailed Description
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The study will consist of a Screening Period, an Open-Label Dose Optimization Phase, a Double-Blind Treatment Phase and a Follow-Up Visit, as follows: Screening Period: Subjects will undergo a screening period up to 49 days prior to entering into the Open-Label Dose Optimization Phase. Open-Label Dose Optimization Phase: During the Dose Optimization Phase, subjects will be titrated to doses of 20, 30 or 40 mg KP415 based on tolerability and best individual dose-response in the opinion of the Investigator. Double-Blind Treatment Phase: Eligible subjects will be randomized to receive single daily doses of KP415 or Placebo for 7 days according to a randomization schedule. The dose of KP415 given in the Treatment Phase will be the same as the optimized dose of KP415 at the end of the Dose Optimization Phase. All subjects will receive their assigned treatment daily for 7 days. The dose will be the same at each day of the Treatment Period. Efficacy and safety assessments will be performed after the last dose of the Treatment Period. Follow-Up Visit: 3 ±2 days after administration of the last dose of the Treatment Phase, subjects will enter a Follow-Up Visit to evaluate safety parameters.

Official Title
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A Multicenter, Dose-Optimized, Double-Blind, Randomized, Placebo-Controlled, Parallel Efficacy Laboratory Classroom Study With KP415 in Children With Attention-Deficit/Hyperactivity Disorder

Conditions
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ADHD

Intervention / Treatment
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* Drug: KP415 oral capsule
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must meet Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5) criteria for a primary diagnosis of ADHD (combined, inattentive, or hyperactive/impulsive presentation) per clinical evaluation and confirmed by the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). Subject must have a score of at least 3 (mildly ill) on the clinician-administered Clinical Global Impressions-Severity (CGI-S) scale. Subject, subject's parent/legal guardian and caregiver (if applicable) must understand and be willing and able to comply with all study procedures and visit schedule. Exclusion Criteria: Subject with any clinically significant chronic medical condition that may interfere with the participant's ability to participate in the study. Subject has any diagnosis of bipolar I or II disorder, major depressive disorder, conduct disorder, obsessive-compulsive disorder, any history of psychosis, autism spectrum disorder, disruptive mood dysregulation disorder (DMDD), intellectual disability, Tourette's Syndrome, confirmed genetic disorder with cognitive and/or behavioral disturbances. Subject has evidence of any chronic disease of the central nervous system (CNS) such as tumors, inflammation, seizure disorder, vascular disorder, potential CNS related disorders that might occur in childhood, or history of persistent neurological symptoms attributable to serious head injury. Subject has a current (last month) psychiatric diagnosis other than specific phobia, motor skills disorders, oppositional defiant disorder, sleep disorders, elimination disorders, adjustment disorders, learning disorders, or communication disorders. Participants with school phobia or separation anxiety will not be eligible. Subject has any history of attempted suicide or clinically significant suicidal ideation or subject has a C-SSRS score for suicidal ideation ≥2. Subject has any clinically significant unstable medical abnormality, chronic disease, or a history of a clinically significant abnormality of the cardiovascular, gastrointestinal, respiratory, hepatic, or renal systems, or a disorder or history of a condition that may interfere with drug absorption, distribution, metabolism, or excretion of study drug. Subject has a history or presence of abnormal ECGs.

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: Parallel Assignment
Interventional Model Description: 3-week, open-label dose-optimization phase followed by a 1-week randomized, double-blind treatment phase
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-blind KP415<br>KP415 (serdexmethylphenidate [SDX] Cl/ d-methylphenidate [d-MPH] HCl) oral capsule: 28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl) | Drug: KP415 oral capsule<br>* Daily dose<br>|
| Placebo Comparator: Double-blind Placebo<br>Placebo oral capsule | Drug: Placebo oral capsule<br>* Daily dose<br>|
| Experimental: Open-Label KP415<br>KP415 (serdexmethylphenidate [SDX] Cl/ d-methylphenidate [d-MPH] HCl) oral capsule: 28/6 mg SDX/d-MPH (molar equivalent to 20 mg d-MPH HCl), 42/9 mg SDX/d-MPH (molar equivalent to 30 mg d-MPH HCl), 56/12 mg SDX/d-MPH (molar equivalent to 40 mg d-MPH HCl) | Drug: KP415 oral capsule<br>* Daily dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Combined Scores | The SKAMP scale is a validated rating of subjective impairment of classroom behaviors in children with ADHD. It comprises 13 items (grouped under the subcategories of attention, deportment, quality of work, and compliance) on which subjects are rated according to a 7-point scale (0 = normal to 6 = maximal impairment) by trained study personnel (Swanson 1998). The SKAMP-C score was obtained by summing the rating values for each of the 13 items (range: 0-78), with higher scores indicating greater impairment. | Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Permanent Product Measure of Performance (PERMP) Rating Scale, Number of Problems Attempted (PERMP-A) | The PERMP is an adjusted math test designed to assess attention in children with ADHD (Swanson 1999). The test measures attention through a subject's ability to initiate, self-monitor, and complete the math test. A Placement PERMP was performed early in the trial to assure that subjects could complete at least the basic level of math problems and to determine the appropriate level of math to be assigned during the remainder of the study. The PERMP is an individually calibrated 5-page mathematics worksheet consisting of 400 problems. PERMP-A scores document the number of problems attempted, from 0 to 400, and thus higher scores represent a better outcome. | Average of all time points during the full laboratory classroom day, which occurred on Day 7 (Day 28 of the overall study) of the Treatment Phase |