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

Attention-Deficit/Hyperactivity Disorder Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04781140
• Other study ID #: 812P401
• Status: Recruiting
• Phase: Phase 4
• Start date: March 19, 2024
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: Supernus Pharmaceuticals, Inc.
• Contact: Joseph T Hull, PhD
• Phone: 240-403-5324
• Email: jhull[@]supernus.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 286
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 48 Months to 69 Months

Eligibility

Inclusion Criteria:

1. Is male or female between 4 years 0 months and 5 years 9 months of age at Screening and considered medically healthy.

2. 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.

3. 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).

4. Has an ADHD-RS-IV-P Total Score of = 28 (males) or = 24 (females) at Screening and at Baseline (Day 1).

5. Has a CGI-S score of = 4 (moderate or worse) at Screening and at Baseline (Day 1).

6. Has undergone an adequate course of non-pharmacologic treatment or is having symptoms severe enough to warrant pharmacologic treatment without prior non-pharmacologic treatment.

7. 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.

8. 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).

9. 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

10. Has no current condition in the opinion of the Investigator that could confound safety assessments or increase participant risk.

11. Has lived with the same parent(s) or legal guardian(s) for greater than or equal to 6 months.

12. Has a body weight =5th percentile for age and sex at Screening and Baseline.

Exclusion Criteria:

1. Has a current diagnosis of a major psychiatric disorder.

2. 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.

3. History of Bipolar Disorder diagnosed in a first degree relative.

4. Has global development delay or intellectual disability by medical history.

5. Has a current diagnosis of a significant (per Investigator's evaluation and/or judgement) systemic disease.

6. Has body mass index > 95th percentile for the subject's age and gender.

7. Has a resting blood pressure and heart rate* measurement (average of the 3 'sitting' vital signs readings) greater than or equal to 95th percentile for age at screening or baseline. * Note: The heart rate obtained during Vital Signs refers to "pulse rate".

8. Has a clinically significant electrocardiogram findings at screening.

9. Has history of allergic reaction, hypersensitivity or intolerance to viloxazine.

10. Has an allergy to applesauce or cannot swallow capsules and applesauce.

11. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in the study.

12. Received any investigational drug within the longer of 30 days or 5 half-lives prior to Day 1 dosing with SM.

13. 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.

14. 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.

15. Any reason that, in the opinion of the Investigator, would prevent the subject from participating in the study.

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention-Deficit/Hyperactivity Disorder
• Hyperkinesis

Intervention

Drug:
• 100mg SPN-812
100mg SPN-812 will be administered once daily and compared to Placebo
• Placebo
Placebo will be administered once daily

Locations

Country	Name	City	State
United States	Center for Psychiatry and Behavioral Medicine	Las Vegas	Nevada

Sponsors (1)

Lead Sponsor	Collaborator
Supernus Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 (Week 6)	The Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) consists of 18 items that correspond directly to the DSM-IV-TR criteria for ADHD. The scale is subdivided into two subscales: inattention ("IA", 9 items) and hyperactivity-impulsivity ("H/I", 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 sum of the ratings of all 18 items yields the raw Total score (range: 0-54; the higher the Total score, the more severe the ADHD symptoms). Post-baseline raw Total scores are converted to a change from baseline Total score. A lower change from baseline ADHD-RS-IV-P Total Score (<0) represents a better outcome.	6 weeks
Secondary	Change from Baseline in the Clinical Global Impression of Severity (CGI-S) Score at End of Study (Week 6)	The Clinical Global Impression of Severity (CGI-S) is a single item clinician-rated assessment of the severity of subject's condition (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, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients (the higher the score, the more severe the overall ADHD symptoms). Post-baseline (raw) CGI-S scores are converted to a change from baseline score. A lower change from baseline CGI-S score (<0) represents a better outcome.	6 Weeks
Secondary	Clinical Global Impression of Change (CGI-C) Score at End of Study (Week 6)	The Clinical Global Impression of Change (CGI-C) is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-C is rated on a 7-point scale from 1 to 7, where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved", 4 = "no change", 5 = "minimally worse", 6 = "much worse", and 7 = "very much worse". A CGI-C score <4 represents a better outcome.	6 weeks
Secondary	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 (Week 6)	The Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) consists of 18 items that correspond directly to the DSM-IV-TR criteria for ADHD. The scale is subdivided into two subscales: inattention ("IA", 9 items) and hyperactivity-impulsivity ("H/I" 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 sum of the nine H/I items yields the raw H/I subscale score (range: 0-27; the higher the H/I subscale score, the more severe the H/I symptoms). Post-baseline raw H/I subscale scores are converted to a change from baseline score. A lower change from baseline H/I subscale score (<0) represents a better outcome.	6 weeks
Secondary	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 (Week 6)	The Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) consists of 18 items that correspond directly to the DSM-IV-TR criteria for ADHD. The scale is subdivided into two subscales: inattention ("IA", 9 items) and hyperactivity-impulsivity ("H/I" 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 sum of the nine IA items yields the raw IA subscale score (range: 0-27; the higher the IA subscale score, the more severe the IA symptoms). Post-baseline raw IA subscale scores are converted to a change from baseline score. A lower change from baseline IA subscale score (<0) represents a better outcome.	6 weeks
Secondary	Clinical Global Impression of Severity (CGI-S) Responder Rate (percentage of subjects with CGI-S score of 1 or 2) at End of Study (Week 6)	The Clinical Global Impression of Severity (CGI-S) is a single item clinician-rated assessment of the severity of subject's condition (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, asymptomatic, 2 = Borderline Ill, 3 = Mildly Ill, 4 = Moderately Ill, 5 = Markedly Ill, 6 = Severely Ill, and 7 = Among the most extremely ill patients. The responder rate (percent) is calculated by dividing "the number of 'responders' (m)" by "the number of subjects analyzed at the respective Visit/Week (n)" and multiplying the product by 100. Responder Rate values range from 0 to 100%. A percent >50% represents a greater number of "responders" versus "non-responders".	6 weeks
Secondary	Clinical Global Impression of Change (CGI-C) Responder Rate (percentage of subjects with CGI-C score of 1 or 2) at End of Study (Week 6)	The Clinical Global Impression of Change (CGI-C) is a single item clinician-rated assessment of how much the subject's condition (ADHD) has improved, worsened or has not changed relative to his/her baseline state prior to the beginning of treatment. The CGI-C is rated on a 7-point scale from 1 to 7, where 1 = "very much improved", 2 = "much improved", 3 = "minimally improved", 4 = "no change", 5 = "minimally worse", 6 = "much worse", and 7 = "very much worse". The responder rate (percent) is calculated by dividing "the number of 'responders' (m)" by "the number of subjects analyzed at the respective Visit/Week (n)" and multiplying the product by 100. Responder Rate values range from 0 to 100%. A percent >50% represents a greater number of "responders" versus "non-responders".	6 weeks
Secondary	Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) Responder Rate (percentage of subjects with = 50% Reduction in Change from Baseline) at End of Study (Week 6)	The Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition, Preschool Version (ADHD-RS-IV-P) consists of 18 items that correspond directly to the DSM-IV-TR criteria for ADHD. The scale is subdivided into two 9 item subscales: inattention and hyperactivity-impulsivity. The clinician rates the frequency and severity of each symptom on a 4-point Likert-type scale; 0 = Never or rarely, 1 = Sometimes, 2 = Often, and 3 = Very often. Sum of 18 ratings yields the Total score (range: 0-54; higher score represents severer symptoms). Percent reduction is calculated for the ADHD-RS-IV-P score: [("Post-baseline"-"Baseline")/"Baseline"] x 100; range: 0 to 100%; a "responder" is a subject with a 50% or greater reduction in change from baseline Total score. Responder rate (percent of responders) is calculated: ["number of 'responders' (m)"/ "number of subjects analyzed" (n)] X 100; range: 0 to 100%. A Responder Rate greater than 50%, represents more "responders" versus "nonresponders".	6 weeks