KP415 Open-Label Safety Study in Children (6-12 Years of Age) With ADHD

Study Overview
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Brief Summary
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This study is a multicenter, dose-optimized, open-label safety 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, a Dose Optimization Phase, and a Treatment Phase and a Follow-Up Visit, as follows: Screening Period: Subjects will undergo a screening period up to 30 days prior to entering the Dose Optimization Phase. 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. Treatment Phase: Eligible subjects will receive single daily doses of KP415 for up to approximately 360 days (up to approximately 12 months). The dose of KP415 given in the Treatment Phase will be the dose of KP415 at the end of the Dose Optimization Phase. During the Treatment Phase, the dose of KP415 may be changed based on individual tolerability and best dose response (to either 20, 30, or 40 mg KP415 capsules). Safety, efficacy and sleep behavior assessments will be performed. 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, Open-Label Safety 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


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. Subjects who completed the efficacy study with KP415 may be rolled over into the current study. 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 clinically significant suicidal ideation/behavior, based on a history of attempted suicide and the C-SSRS assessment at Screening or at any time before the last dose of study drug. 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 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>* Once-daily oral dose<br>* Other names: SDX/d-MPH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects With Treatment-Emergent Adverse Events (TEAEs) | TEAEs will be assessed starting following the first dose of study drug, and ending with the Follow-Up Visit or Early Termination Visit. | Up to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in ADHD-RS-5 Total Score | The clinician-administered ADHD-RS-5 is an 18-item scale that rates ADHD symptoms on a 4-point scale. Each item is scored using a combination of severity and frequency ratings from a range of 0 (reflecting no symptoms or a frequency of never or rarely) to 3 (reflecting severe symptoms or a frequency of very often), so that the total ADHD-RS-5 scores range from 0 to 54. The 18 items can be divided into two 9-item subscales: One for hyperactivity/impulsivity and the other for inattentiveness. | Up to 12 months | 
| Change From Baseline in CGI-S | The CGI-S is a clinician-rated scale that evaluates the severity of psychopathology (ADHD symptoms in this study) on a scale from 1 (not at all ill) to 7 (among the most severely ill). | Up to 12 months | 
| Change From Baseline in Children's Sleep Habits Questionnaire | The modified, abbreviated Children's Sleep Habits Questionnaire (CSHQ) will be used to assess the sleep behavior. The CSHQ is a retrospective, 33-item parent questionnaire to examine sleep behavior in small children. Items are rated on a 3-point scale of Usually, Sometimes and Rarely for occurrences in a number of key sleep domains: bedtime resistance, sleep onset delay, sleep duration, sleep anxiety, night wakings, parasomnias, sleep disordered breathing, and daytime sleepiness. Scores range from 33-99, with higher scores represent more disturbed sleep. Scores were obtained during a clinician-directed interview with the parent/guardian/caregiver. | Up to 12 months |