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

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.

Inclusion criteria

• Is male or female 4 years 0 months of age to less than or equal to 5 years 9 months of age at Visit 1 (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 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 Visit 1 (Screening) and at Visit 2 (Baseline).
• Has a CGI-S score of ≥ 4 (moderate or worse) at Visit 1 (Screening) and at Visit 2 (Baseline).
• 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, summer camp or childcare program) at least 2 days a week during study so as to assess symptoms and impairment in a setting outside the home.
• Has not initiated any behavioral intervention/therapy within 30 days of Visit 1 (Screening) and does not plan to initiate any new or discontinue any ongoing behavioral intervention/therapy during the study (e.g., subject is eligible if behavioral intervention/therapy is initiated 30 or more days prior to Visit 1 [Screening] and continues with a similar duration/frequency throughout their study).
• Subjects who are on ADHD medication at Visit 1 (Screening), but whose ADHD symptoms are not well controlled on current ADHD medication (e.g., meets Inclusion Criterion #4), meet all other inclusion/exclusion criteria, and discontinues ADHD medication at least 7 days prior to the day of Visit 2 (Baseline) are eligible to participate.
• Has no current condition in the opinion of the Investigator that could confound efficacy assessments, safety assessments or increase participant risk.
• Has lived with the same parent(s) or legal guardian(s) or has lived under a shared living arrangement (e.g., joint legal custody) for greater than or equal to 6 months prior to Visit 1 (Screening).
• Has a body weight ≥5th percentile for age and sex at Visit 1 (Screening) and Visit 2 (Baseline).

Exclusion criteria

• Has a diagnosis at Screening (per K-SADS-PL) of another psychiatric disorder that is considered to be the primary diagnosis rather than ADHD or has a comorbid psychiatric disorder secondary to ADHD that, in the opinion of the investigator (after consulting medical monitor), will likely interfere with study treatment adherence and/or impact study results.
• Has a current diagnosis of a major neurological disorder. The eligibility of those who have seizures, a history of seizure-like events (e.g., syncope, myoclonus, severe muscle spasms), a family history of seizure disorder (immediate family, i.e., sibling, parent), and/or febrile seizures will be assessed on a case-by-case basis after consulting the medical monitor.
• History of Bipolar Disorder diagnosed in a first degree relative.
• Has global development delay or intellectual disability by medical history.
• Has a current diagnosis of a significant (per Investigator's evaluation and/or judgement) systemic disease.
• Has body mass index > 95th percentile for the subject's age and sex at Visit 1 (Screening) or Visit 2 (Baseline).
• Has a mean resting systolic and diastolic blood pressure* that are both >95th percentile for age sex, and height and has a mean resting pulse rate* that is >95th percentile for age and sex (males: >117 bpm; females: >122 bpm) at Visit 1 (Screening) or Visit 2 (Baseline). * Note: The mean of three measurements while seated.
• Has a clinically significant electrocardiogram finding(s) at Visit 1 (Screening).
• Is currently taking SPN-812 for ADHD, has previously taken SPN-812 for ADHD, but discontinued due to a lack of efficacy or adverse reactions, or has history of allergic reaction, hypersensitivity or intolerance to viloxazine.
• Has an allergy to or cannot swallow pudding and applesauce and cannot swallow intact capsule whole.
• Has any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in the study.
• Has received any investigational drug within the longer of 30 days or 5 half-lives prior to Visit 2 (e.g., first dose of study medication).
• Has a positive urine drug test at Visit 1 (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 7 days prior to Visit 2 (Baseline).
• Is using 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.
• Has suicidal ideation ("Yes" indicated on C-SSRS question 4 or 5) or suicidal behavior ("Yes" indicated on C-SSRS for any suicidal behavior) within 6 months prior to or the day of Visit 1 (Screening) or has attempted suicide ("Yes" indicated on C-SSRS for lifetime).