Evaluation of SPN-812 (Viloxazine Extended-release Capsule) in Preschool-age Children With ADHD

Study Overview
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Brief Summary
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This study will evaluate the efficacy and safety of SPN-812 (viloxazine extended release) in children 4 to 5 years of age with ADHD.

Detailed Description
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This is a randomized, double-blind, placebo-controlled, multicenter, 2-arm (1:1), parallel-group, efficacy and safety/tolerability fixed-dose study of SPN-812 in preschool-age children (4 to 5 years old) with ADHD. Participants will be screened for eligibility for up to 4 weeks. Eligible participants will be treated with study medication for 6 weeks. The total duration of the study is up to 10 weeks.

Official Title
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A Phase 4, Randomized, Double-Blind, Multicenter, Placebo-Controlled, Parallel-Group Study of the Efficacy and Safety of SPN-812 in Preschool-Age Children (4 to 5 Years Old) With Attention-Deficit/Hyperactivity Disorder (ADHD)

Conditions
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Attention-Deficit/Hyperactivity Disorder

Intervention / Treatment
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* Drug: 100mg SPN-812
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Is male or female, between 4 years 0 months and 5 years 9 months of age at Screening and considered medically healthy. Subject's parent(s) or legal guardian(s)/representative(s) is (are) willing and able to provide written informed consent, including a signed Informed Consent Form and documentation of assent (if applicable) by the subject before completing any study related procedures. Has a primary diagnosis of ADHD according to DSM-IV-TR criteria, and confirmed with the Kiddie Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version (K-SADS-PL). Has an ADHD-RS-IV-P Total Score of ≥ 28 (males) or ≥ 24 (females) at Screening and at Baseline (Day 1). Has a CGI-S score of ≥ 4 (moderately ill or worse) at Screening and at Baseline (Day 1). Has undergone an adequate course of non-pharmacologic treatment or is having symptoms severe enough to warrant pharmacologic treatment without prior non-pharmacologic treatment. Is participating in a structured group activity (e.g., preschool, kindergarten, sports, Sunday school or child care program) so as to assess symptoms and impairment in a setting outside the home. Is not currently receiving a behavioral intervention for ADHD at the time of screening nor plans to receiving a behavioral intervention for ADHD throughout their study (if subject is receiving a behavioral interventions for another psychiatric disorder or disorders, their eligibility will be evaluated on a case-by-case basis). For subjects who are on ADHD medication at screening, but who's ADHD symptoms are not well controlled on current ADHD medication are allowed in the study if they meet all other inclusion/exclusion criteria. Has no current condition in the opinion of the Investigator that could confound safety assessments or increase participant risk. Has lived with the same parent(s) or legal guardian(s) for greater than or equal to 6 months. Has a body weight ≥5th percentile for age and sex at Screening and Baseline. Exclusion Criteria: Has a current diagnosis of a major psychiatric disorder. Has a current diagnosis of a major neurological disorder. Subjects with seizures or with a history of seizure-like events, or with a family history of seizure disorder (immediate family, i.e., sibling, parent) are excluded. Febrile seizures are not exclusionary and will be assessed on a case-by-case basis, however, a history of complex febrile seizures is exclusionary. If for any reason the subject received medication for a febrile seizure, this will be exclusionary. History of Bipolar Disorder diagnosed in a first degree relative. Has global developmental delay or intellectual disability by medical history. Has a current diagnosis of a significant (per Investigator's evaluation and/or judgement) systemic disease. Has a body mass index > 95th percentile for the subject's age and gender. Has a blood pressure and heart rate measurement greater than or equal to 95th percentile for age at screening or baseline. Has a clinically significant electrocardiogram findings at screening. Has a history of allergic reaction, hypersensitivity or intolerance to viloxazine. Has an allergy to applesauce or cannot swallow capsules and applesauce. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in the study. Received any investigational drug within the longer of 30 days or 5 half-lives prior to Day 1 dosing with SM. Positive drug test at Screening. A positive test for amphetamines is allowed for subjects receiving a stimulant ADHD medication at Screening. The subject will be required to discontinue the stimulant for the duration of the study, beginning at least 1 week prior to the Baseline Visit. Use of prohibited concomitant medications including known CYP1A2 substrates (e.g., theophylline, melatonin) during the screening period or anticipated for the duration of the study Any reason that, in the opinion of the Investigator, would prevent the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 48 Months
Maximum Age: 69 Months

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo, qd | Drug: Placebo<br>* Placebo will be administered once daily<br>|
| Experimental: SPN-812<br>SPN-812, qd | Drug: 100mg SPN-812<br>* 100mg SPN-812 will be administered once daily and compared to Placebo<br>* Other names: SPN-812;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of SPN-812 on ADHD symptoms as assessed by the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P). | Change from Baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) Total Score at End of Study. The ADHD-RS-IV-P consists of 18 items that correspond directly to the DSM-IV-TR criteria for ADHD and are also subdivided into two subscales: inattention (9 items) and hyperactivity-impulsivity (9 items).The clinician rates the frequency and severity of each symptom on a 4-point Likert-type scale, where 0 = Never or rarely, 1 = Sometimes, 2 = Often, and 3 = Very often. The Total Score is the summation of all 18 items ranging from 0 and 54, and subscale scores are the summation of 9 items ranging from 0 and 27 for both Inattention and Hyperactivity/Impulsivity. Lower scores represent a better outcome. | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of SPN-812 on the global assessment of severity of illness as assessed by the Clinical Global Impression - Severity of Illness (CGI-S) Scale. | Change from Baseline in the Clinical Global Impression - Severity of Illness (CGI-S) Score at End of Study. The CGI-S is a single item clinician rating of clinician's assessment of the severity of the ADHD symptoms in relation to the clinician's total experience with patients with ADHD. The CGI-S is evaluated on a 7-point scale with 1 = Normal, not at all ill, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Extremely Ill. Successful therapy is indicated by a lower overall score in subsequent testing. | 6 Weeks | 
| Effect of SPN-812 on the global assessment of improvement as assessed by the Clinical Global Impression - Improvement (CGI-I) Scale. | Clinical Global Impression - Improvement (CGI-I) Score at End of Study.The CGI-I is an assessment of how much the patient's illness has improved or worsened relative to a baseline state at the beginning of treatment. The CGI-I is evaluated on a 7-point scale with 1 = Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = Minimally worse, 6 = Much worse, and 7 = Very much worse. Successful therapy is indicated by a lower overall score in subsequent testing. | 6 weeks | 
| Effect of SPN-812 on the clinical response rate of improvement assessed by the categorical Clinical Global Impression - Improvement (CGI-I) responder rate. | Percentage of Subjects with a Clinical Global Impression - Improvement (CGI-I) score of 1 or 2 at End of Study. The higher percentage (0 to 100%) represents more treatment responders. | 6 weeks | 
| Effect of SPN-812 on the clinician response rate as measured by 50% Responder Rate on the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) | Percentage of Subjects with a Response Rate Defined as ≥ 50% Reduction in Change from Baseline (CFB) Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) Total Score at End of Study (EOS). The higher percentage (0 to 100%) represents more treatment responders. | 6 weeks | 
| Effect of SPN-812 on symptoms of Hyperactivity/Impulsivity as assessed by the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) Hyperactivity/Impulsivity Subscale. | Change from Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) Hyperactivity/Impulsivity Subscale Score at End of Study. The ADHD-RS-IV-P consists of 18 items that correspond directly to the DSM-IV-TR criteria for ADHD and are also subdivided into two subscales: inattention (9 items) and hyperactivity-impulsivity (9 items).The clinician rates the frequency and severity of each symptom on a 4-point Likert-type scale, where 0 = Never or rarely, 1 = Sometimes, 2 = Often, and 3 = Very often. The Total Score is the summation of all 18 items ranging from 0 and 54, and subscale scores are the summation of 9 items ranging from 0 and 27 for both Inattention and Hyperactivity/Impulsivity. Lower scores represent a better outcome. | 6 weeks | 
| Effect of SPN-812 on symptoms of Inattention as assessed by the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) Inattention Subscale. | Change from Baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) Inattention Subscale Score at End of Study. The ADHD-RS-IV-P consists of 18 items that correspond directly to the DSM-IV-TR criteria for ADHD and are also subdivided into two subscales: inattention (9 items) and hyperactivity-impulsivity (9 items).The clinician rates the frequency and severity of each symptom on a 4-point Likert-type scale, where 0 = Never or rarely, 1 = Sometimes, 2 = Often, and 3 = Very often. The Total Score is the summation of all 18 items ranging from 0 and 54, and subscale scores are the summation of 9 items ranging from 0 and 27 for both Inattention and Hyperactivity/Impulsivity. Lower scores represent a better outcome. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ADHD