Efficacy and Safety of SPN-812 (Viloxazine Extended-release Capsule) in Children With ADHD

Study Overview
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Brief Summary
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This was a randomized, double-blind, placebo-controlled, multicenter, 5-arm, parallel-group, dose-ranging study to assess the efficacy and safety of SPN-812 (Viloxazine Extended-release Capsule) in children 6-12 years of age with ADHD.

Detailed Description
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This study is a randomized, double-blind, placebo-controlled, multicenter, 5-arm, parallel-group, dose-ranging study to assess the efficacy, safety, and tolerability of SPN-812 (Viloxazine Extended-release Capsule) as monotherapy in the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD) in children (6-12 years of age). Subjects are randomized in a 1:2:2:2:2 ratio to receive placebo or one of four active treatments (100 mg, 200 mg, 300 mg, or 400 mg SPN-812). The primary objective is to assess the efficacy of SPN-812 in reducing ADHD symptoms as measured by the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV).

Official Title
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Evaluation of the Efficacy and Safety of SPN-812 (Viloxazine Extended-release Capsule) in Children With ADHD - A Double-Blind, Placebo-Controlled, Dose-Ranging Study

Conditions
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Attention-Deficit/Hyperactivity Disorder (ADHD)

Intervention / Treatment
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* Drug: Placebo
* Drug: 100mg SPN-812
* Drug: 200mg SPN-812
* Drug: 300mg SPN-812
* Drug: 400mg SPN-812


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female subjects, 6-12 years of age, inclusive, with a diagnosis of ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-IV (DSM IV), confirmed with the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID). ADHD-RS-IV-Parent Version: Investigator Administered and Scored score of at least 26. CGI-S score of at least 4 Weight of at least 20 kg. Free of medication for the treatment of ADHD or any psychosis for at least one week prior to enrollment. Exclusion Criteria: Current or lifetime diagnosis of major depressive disorder, bipolar disorder, personality disorder, Tourette's disorder, or psychosis not otherwise specified. Currently meeting DSM-IV criteria for pervasive developmental disorder, obsessive compulsive disorder, post-traumatic stress disorder, or any other anxiety disorder as primary diagnosis. Significant systemic disease. Evidence of suicidality within the six months before Screening or at Screening. BMI greater than 95th percentile for the appropriate age and gender. Pregnancy or refusal to practice abstinence during the study for female subjects of childbearing potential (FOCP). Substance or alcohol use during the last three months. Positive urine screen for cotinine, alcohol, or drugs of abuse at Screening.

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo, qd, oral capsule | Drug: Placebo<br>* Placebo was administered once daily<br>* Other names: PBO;|
| Experimental: 100mg SPN-812<br>100mg SPN-812, qd, oral capsule | Drug: 100mg SPN-812<br>* 100mg SPN-812 was administered once daily and compared to placebo<br>* Other names: SPN-812, Low Dose;|
| Experimental: 200mg SPN-812<br>200mg SPN-812, qd, oral capsule | Drug: 200mg SPN-812<br>* 200mg SPN-812 was administered once daily and compared to placebo<br>* Other names: SPN-812, Low-Medium Dose;|
| Experimental: 300mg SPN-812<br>300mg SPN-812, qd, oral capsule | Drug: 300mg SPN-812<br>* 300mg SPN-812 was administered once daily and compared to placebo<br>* Other names: SPN-812, Medium-High Dose;|
| Experimental: 400mg SPN-812<br>400mg SPN-812, qd, oral capsule | Drug: 400mg SPN-812<br>* 400mg SPN-812 was administered once daily and compared to placebo<br>* Other names: SPN-812, High Dose;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Efficacy of SPN-812 on the Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) | The Primary Endpoint was the change from baseline in Attention-Deficit/Hyperactivity Disorder Rating Scale, 4th Edition (ADHD-RS-IV) Total score at Week 8 (End of Study). The ADHD-RS-IV is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. The scale consists of 18 items that directly correspond to the 18 Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) symptoms of ADHD. Each item is rated on a 4-point Likert-type scale from 0 (never or rarely) to 3 (very often). A Total score is calculated by adding the responses of all 18 items (range: 0-54; the higher the score, the more severe the ADHD symptoms). Lower change from baseline scores (<0) represent a better outcome. | Baseline to Week 8 (End of Study) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of SPN-812 on Clinical Global Impression - Improvement (CGI-I) Scale | The first additional secondary endpoint was the Clinical Global Impression-Improvement (CGI-I) Scale score at Week 8 (End of Study). The CGI-I scale is a single item assessment of how much the patient's illness has improved or worsened relative to a baseline state prior to the beginning of treatment. The CGI-I is rated on a 7-point Likert 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. Successful therapy is indicated by a lower score (<4) in subsequent testing. | Week 8 (End of Study) | 
| Effect of SPN-812 on the Clinical Global Impression - Severity (CGI-S) Scale | The second additional secondary endpoint was the change from baseline in the Clinical Global Impression-Severity (CGI-S) Scale score at Week 8 (End of Study). The CGI-S scale is a single item clinician/investigator rating of the 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 was rated on a 7-point Likert scale, where 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 CGI-S score in subsequent testing. A lower change from baseline score (<0) represents a better outcome. | Baseline to Week 8 (End of Study) |