100mg SPN-812 was administered once daily and compared to placebo

200mg SPN-812 was administered once daily and compared to placebo

The second Key Secondary Endpoint was the change from baseline in the Conners 3rd Edition - Parent Short Form (C3PS) Composite T-score at Week 6 (End of Study). The Conners 3rd Edition is a focused diagnostic tool for the assessment of ADHD and associated learning, behavior, and emotional problems in children 6 to 18 years of age. The C3PS is completed by a child's parent/guardian and is comprised of 45 items with subsets of items related to six content scales: inattention, hyperactivity/impulsivity, executive functioning, learning problems, defiance/aggression and peer relations. The parent rates his/her child on the first 43 items of the C3PS using a 4-point Likert scale (0-3; where 0=not at all true [never, seldom] and 3=very much true [very often, very frequently]) based on past month; the last 2 items are fill-in-the-blank and do not contribute to the raw score(s). Raw scores are converted to T-scores. Lower change from baseline T-scores (<0) represent a better outcome.

The third Key Secondary Endpoint was the change from baseline in the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) Total Average score at Week 6 (End of Study). The WFIRS instrument evaluates ADHD-related functional impairment. The WFIRS-P is completed by the child's parent/guardian and is comprised of 50 items grouped into six domains: Family (10 items), School (10 items, includes learning [4 items] and behavior [6 items]), Life Skills (10 items), Child's Self-Concept (3 items), Social Activities (7 items), and Risky Activities (10 items). The parent/guardian rates each item on a 4-point Likert scale (0-3; where 0=never or not at all to 3= very often or very much) based on their child's behavior past month. A Total Average score was computed by calculating mean rating of all 50 items (ranging from 0 to 3, where a higher value represents more severe functional impairment). Lower change from baseline Total Average scores (<0) represent a better outcome.

An additional secondary endpoint was the percentage of responders at Week 6 (End of Study). A responder was defined as a subject who had a 50% or greater reduction (improvement) in their change from baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Total score at Week 6 (End of Study). Values range from 0 to 100%. A higher percentage represents a greater number of responders.

An additional secondary endpoint was the change from baseline in Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) Total score at Week 6 (End of Study). The PSI-4 questionnaire evaluates the magnitude of stress in the parent-child relationship based on the parent's perception of the child's characteristics, the personal characteristics of the parent, and the interaction between the parent and the child. The PSI-4-SF was developed for parents of children ages 1 month to 12 years. The PSI-4-SF consists of 36 items divided into three domains: parental distress, parent-child dysfunctional interaction, and difficult child. Each item is rated on a 5-point Likert scale, where SD=Strongly Disagree, D=Disagree, NS=Not Sure, A=Agree, and SA=Strongly Agree. The total score ranges between 90 and 450; higher total scores indicate higher levels of stress. Lower change from baseline total scores (<0) represent better outcome.

An additional secondary endpoint was the change from baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Hyperactivity/Impulsivity subscale score and Inattention subscale score at Week 6 (End of Study). The ADHD-RS-5 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 DSM-5 symptoms of ADHD, including 9 items for the Hyperactivity/Impulsivity subscale and 9 items for the Inattention subscale. Each item is rated on a 4-point Likert-type scale from 0 (never or rarely) to 3 (very often). Each subscale score is calculated by adding the responses of all respective 9 items (range: 0-27; the higher the subscale score, the more severe the Hyperactivity/Impulsivity or Inattention symptoms). Lower change from baseline subscale scores (<0) represent a better outcome.

An additional secondary endpoint was the change from baseline in the Conners 3rd Edition - Self Report Short Form (C3-SRS) Composite T score at Week 6 (End of Study). The Conners 3rd Edition is a focused diagnostic tool for assessment of ADHD and associated learning, behavior, and emotional problems in children 6 to 18 years of age. The C3-SRS, which is only validated in children/adolescents 8-18 years of age, is comprised of 41 items with subsets of items related to five content scales: inattention, hyperactivity/impulsivity, learning problems, aggression and family relations. The subject rates himself/herself on the first 39 items of C3-SRS using a 4-point Likert scale (0-3; where 0=not at all true [never, seldom] and 3=very much true [very often, very frequently] based on past month; the last 2 items are fill-in-the-blank and do not contribute to the raw score(s). Raw scores are converted to T-scores. Lower change from baseline T-scores (<0) represent a better outcome.

An additional secondary endpoint was the percentage of subjects who were "improved" by visit; "improved" was defined as a subject who had a Clinical Global Impression - Improvement (CGI-I) score of 1 = "Very Much Improved" or 2 = "Much Improved". Values range from 0 to 100%. A higher percentage represents a greater number of subjects who were "improved".

SPN-812 oral capsule

Treatment C: 200mg SPN-812 was administered once daily and compared to placebo

Total of all reporting groups

The Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. It consists of 18 items that correspond to the 18 ADHD symptoms per the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5). Each item is rated on a 4-point Likert-type scale from 0 (never or rarely) to 3 (very often). Total score = sum of 18 items (range: 0 to 54). The higher the score, the more severe the ADHD symptoms (a total score >=28 was an inclusion criterion of this study).

The Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. It consists of 18 items that correspond to 18 ADHD symptoms per DSM-5, including 9 items for the Hyperactivity/Impulsivity (HI) subscale and 9 items for the Inattention (IA) subscale. Each item is rated on a 4-point Likert-type scale from (0=never or rarely to 3=very often). The IA Subscale score = sum of all 9 IA items on the ADHD-RS-5 (range: 0 to 27). The higher the score, the more severe the IA symptoms of ADHD.

The Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) is an ADHD-specific rating scale designed and validated to assess current ADHD symptomatology. It consists of 18 items that correspond to 18 ADHD symptoms per DSM-5, including 9 items for the Hyperactivity/Impulsivity (HI) subscale and 9 items for the Inattention (IA) subscale. Each item is rated on a 4-point Likert-type scale (0=never or rarely to 3=very often). The HI Subscale score = the sum of all 9 HI items on the ADHD-RS-5 (range: 0 to 27). The higher the score, the more severe the HI symptoms of ADHD.

The first Key Secondary Endpoint was the Clinical Global Impression-Improvement (CGI-I) Scale score at Week 6 (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" and 7 = "very much worse." Successful therapy is indicated by a lower overall score in subsequent testing.

Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.

The second Key Secondary Endpoint was the change from baseline in the Conners 3rd Edition - Parent Short Form (C3PS) Composite T-score at Week 6 (End of Study). The Conners 3rd Edition is a focused diagnostic tool for the assessment of ADHD and associated learning, behavior, and emotional problems in children 6 to 18 years of age. The C3PS is completed by a child's parent/guardian and is comprised of 45 items with subsets of items related to six content scales: inattention, hyperactivity/impulsivity, executive functioning, learning problems, defiance/aggression and peer relations. The parent rates his/her child on the first 43 items of the C3PS using a 4-point Likert scale (0-3; where 0=not at all true [never, seldom] and 3=very much true [very often, very frequently]) based on past month; the last 2 items are fill-in-the-blank and do not contribute to the raw score(s). Raw scores are converted to T-scores. Lower change from baseline T-scores (<0) represent a better outcome.

Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.

The third Key Secondary Endpoint was the change from baseline in the Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) Total Average score at Week 6 (End of Study). The WFIRS instrument evaluates ADHD-related functional impairment. The WFIRS-P is completed by the child's parent/guardian and is comprised of 50 items grouped into six domains: Family (10 items), School (10 items, includes learning [4 items] and behavior [6 items]), Life Skills (10 items), Child's Self-Concept (3 items), Social Activities (7 items), and Risky Activities (10 items). The parent/guardian rates each item on a 4-point Likert scale (0-3; where 0=never or not at all to 3= very often or very much) based on their child's behavior past month. A Total Average score was computed by calculating mean rating of all 50 items (ranging from 0 to 3, where a higher value represents more severe functional impairment). Lower change from baseline Total Average scores (<0) represent a better outcome.

Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.

An additional secondary endpoint was the percentage of responders at Week 6 (End of Study). A responder was defined as a subject who had a 50% or greater reduction (improvement) in their change from baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Total score at Week 6 (End of Study). Values range from 0 to 100%. A higher percentage represents a greater number of responders.

Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.

An additional secondary endpoint was the change from baseline in Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) Total score at Week 6 (End of Study). The PSI-4 questionnaire evaluates the magnitude of stress in the parent-child relationship based on the parent's perception of the child's characteristics, the personal characteristics of the parent, and the interaction between the parent and the child. The PSI-4-SF was developed for parents of children ages 1 month to 12 years. The PSI-4-SF consists of 36 items divided into three domains: parental distress, parent-child dysfunctional interaction, and difficult child. Each item is rated on a 5-point Likert scale, where SD=Strongly Disagree, D=Disagree, NS=Not Sure, A=Agree, and SA=Strongly Agree. The total score ranges between 90 and 450; higher total scores indicate higher levels of stress. Lower change from baseline total scores (<0) represent better outcome.

Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.

An additional secondary endpoint was the change from baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Hyperactivity/Impulsivity subscale score and Inattention subscale score at Week 6 (End of Study). The ADHD-RS-5 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 DSM-5 symptoms of ADHD, including 9 items for the Hyperactivity/Impulsivity subscale and 9 items for the Inattention subscale. Each item is rated on a 4-point Likert-type scale from 0 (never or rarely) to 3 (very often). Each subscale score is calculated by adding the responses of all respective 9 items (range: 0-27; the higher the subscale score, the more severe the Hyperactivity/Impulsivity or Inattention symptoms). Lower change from baseline subscale scores (<0) represent a better outcome.

Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.

An additional secondary endpoint was the change from baseline in the Conners 3rd Edition - Self Report Short Form (C3-SRS) Composite T score at Week 6 (End of Study). The Conners 3rd Edition is a focused diagnostic tool for assessment of ADHD and associated learning, behavior, and emotional problems in children 6 to 18 years of age. The C3-SRS, which is only validated in children/adolescents 8-18 years of age, is comprised of 41 items with subsets of items related to five content scales: inattention, hyperactivity/impulsivity, learning problems, aggression and family relations. The subject rates himself/herself on the first 39 items of C3-SRS using a 4-point Likert scale (0-3; where 0=not at all true [never, seldom] and 3=very much true [very often, very frequently] based on past month; the last 2 items are fill-in-the-blank and do not contribute to the raw score(s). Raw scores are converted to T-scores. Lower change from baseline T-scores (<0) represent a better outcome.

Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment. There is a lower 'N' for this scale because the scale was only completed by subjects 8 to 11 years of age, since this specific scale is only validated in children 8-18 years of age.

An additional secondary endpoint was the percentage of subjects who were "improved" by visit; "improved" was defined as a subject who had a Clinical Global Impression - Improvement (CGI-I) score of 1 = "Very Much Improved" or 2 = "Much Improved". Values range from 0 to 100%. A higher percentage represents a greater number of subjects who were "improved".

Intent-to-Treat (ITT) Population: The ITT population includes subjects who were randomized, took at least one dose of study medication, have a baseline Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) assessment and have at least one post-baseline ADHD-RS-5 assessment.

SPN-812 oral capsule

Treatment B: 100mg SPN-812 administered once daily and compared to placebo

SPN-812 oral capsule

Treatment C: 200mg SPN-812 administered once daily and compared to placebo

This analysis pertains to the Hyperactivity/Impulsivity subscale score

This analysis pertains to the Hyperactivity/Impulsivity subscale score

This analysis pertains to Week 3 of treatment

This analysis pertains to Week 4 of treatment

This analysis pertains to Week 5 of treatment

This analysis pertains to Week 6 of treatment

This analysis pertains to Week 1 of treatment

This analysis pertains to Week 2 of treatment

This analysis pertains to Week 3 of treatment

This analysis pertains to Week 4 of treatment

This analysis pertains to Week 5 of treatment

This analysis pertains to Week 6 of treatment