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This study will evaluate the efficacy and safety of low doses of SPN-812 in adolescents 12-17 years of age.
This is a multicenter, randomized, double-blind, placebo-controlled, 3-arm, parallel-group study, to assess the efficacy and safety of SPN-812 as monotherapy for the treatment of adolescents 12-17 years old with ADHD.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo, qd, oral capsule |
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| 200mg SPN-812 | Experimental | 200mg SPN-812, qd, oral capsule |
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| 400mg SPN-812 | Experimental | 400mg SPN-812, qd, oral capsule |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Drug | Placebo was administered once daily |
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| Measure | Description | Time Frame |
|---|---|---|
| Efficacy of SPN-812 Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) | The Primary Endpoint was the change from baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Total 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 Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) 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 and Week 6 (End of Study) |
| Measure | Description | Time Frame |
|---|---|---|
| Effect of SPN-812 Assessed by Clinical Global Impression-Improvement (CGI-I) Scale | 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. |
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Inclusion Criteria:
Healthy male or female subjects, 12-17 years of age, inclusive.
Diagnosis of ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5), confirmed with the Mini International Neuropsychiatric Interview for Children and Adolescents (MINI-KID).
Attention Deficit/Hyperactivity Disorder Rating Scale-5-Home Version: Adolescent, Investigator Administered and Scored (ADHD-RS-5) score of at least 28.
CGI-S score of at least 4 at screening.
Weight of at least 35 kg.
Free of medication for the treatment of ADHD for at least one week prior to randomization and agreement to remain so throughout the study.
Considered medically healthy by the Investigator via assessment of physical examination, medical history, clinical laboratory tests, vital signs, and electrocardiogram.
Written informed consent obtained from the subject's parent or legal representative and informed assent from the subject, if applicable.
Females of childbearing potential (FOCP) must be either sexually inactive (abstinent) or, if sexually active, must agree to use one of the following acceptable birth control methods beginning 30 days prior to the first dose, throughout the study:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stefan Schwabe | Supernus Pharmaceuticals, Inc. | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Harmonex Neuroscience Research | Dothan | Alabama | 36303 | United States | ||
| Neuropsychiatric Research Center of Orange County |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36847750 | Derived | Faraone SV, Gomeni R, Hull JT, Busse GD, Lujan B, Rubin J, Nasser A. Response of peer relations and social activities to treatment with viloxazine extended-release capsules (Qelbree(R) ): A post hoc analysis of four randomized clinical trials of children and adolescents with attention-deficit/hyperactivity disorder. Brain Behav. 2023 Apr;13(4):e2910. doi: 10.1002/brb3.2910. Epub 2023 Feb 27. | |
| 34523063 |
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| ID | Title | Description |
|---|---|---|
| FG000 | Placebo | Placebo oral capsule Treatment A: Placebo will be administered once daily |
| FG001 | 200mg SPN-812 | 200mg SPN-812 oral capsule Treatment B: SPN-812 was administered once daily and compared to placebo |
| Title | Milestones | Reasons Not Completed | ||||
|---|---|---|---|---|---|---|
| Overall Study |
|
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Sep 18, 2018 | May 7, 2021 |
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| 200mg SPN-812 | Drug | 200mg SPN-812 was administered once daily and compared to placebo |
|
|
| 400mg SPN-812 | Drug | 400mg SPN-812 was administered once daily and compared to placebo |
|
|
| Week 6 (End of Study) |
| Effect of SPN-812 Assessed by Conners 3rd Edition - Parent Short Form (C3-PS) | 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. | Baseline and Week 6 (End of Study) |
| Effect of SPN-812 Assessed by Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) | 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. | Baseline and Week 6 (End of Study) |
| Effect of SPN-812 Assessed by 50% Responder Rate Per the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) | 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. | Week 6 (End of Study) |
| Effect of SPN-812 Assessed by Stress Index for Parents of Adolescents (SIPA) | Another secondary endpoint was the change from baseline in the Stress Index for Parents of Adolescents (SIPA) Total score to Week 6 (End of Study). The SIPA is a 112-item screening/diagnostic instrument for parents of adolescents 11-19 years of age that identifies areas of stress in parent-adolescent interactions. Items 1-90 are rated on a 5-point Likert scale (where SD=Strongly Disagree, D=Disagree, NS=Not Sure, A=Agree, and SA=Strongly Agree) and yields a raw score for 3 Domains (Adolescent Domain, Parent Domain, and Adolescent-Parent Domain) that focus on a parent's perception of their child's personality and on the parent's characteristics and behaviors. The sum of the 3 Domain scores yields the Total (Parent Stress) score (range: 90-450; higher total scores indicate higher levels of stress). Lower change from baseline scores (<0) represent a better outcome. | Baseline and Week 6 (End of Study) |
| Effect of SPN-812 Assessed by the Hyperactivity/Impulsivity Subscale and the Inattention Subscale of the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) | 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. | Baseline and Week 6 (End of Study) |
| Effect of SPN-812 Assessed by Conners 3rd Edition - Self Report Short Form (C3-SRS) | 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. | Baseline and Week 6 (End of Study) |
| Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"] | 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". | Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 |
| Orange |
| California |
| 92868 |
| United States |
| Indago Research & Health Center, Inc. | Hialeah | Florida | 33012 | United States |
| Clinical Neuroscience Solutions, Inc | Jacksonville | Florida | 32217 | United States |
| Miami Clinical Research | Miami | Florida | 33155 | United States |
| Advanced Clinical Research | Meridian | Idaho | 83642 | United States |
| Icahn School of Medicine at Mount Sinai | New York | New York | 10029 | United States |
| Finger Lakes Clinical Research | Rochester | New York | 14618 | United States |
| Clinical Neuroscience Solutions, Inc. | Memphis | Tennessee | 38119 | United States |
| Texas Physicians Medical Research Group | Arlington | Texas | 76014 | United States |
| Houston Clinical Trials | Houston | Texas | 77098 | United States |
| Family Psychiatry of the Woodlands | The Woodlands | Texas | 77381 | United States |
| Derived |
| Faraone SV, Gomeni R, Hull JT, Busse GD, Melyan Z, Rubin J, Nasser A. Executive Function Outcome of Treatment with Viloxazine Extended-Release Capsules in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Post-Hoc Analysis of Four Randomized Clinical Trials. Paediatr Drugs. 2021 Nov;23(6):583-589. doi: 10.1007/s40272-021-00470-2. Epub 2021 Sep 15. |
| 33971070 | Derived | Nasser A, Kosheleff AR, Hull JT, Liranso T, Qin P, Busse GD, Fava M, Maletic V, Rubin J, Lopez F. Evaluating the likelihood to be helped or harmed after treatment with viloxazine extended-release in children and adolescents with attention-deficit/hyperactivity disorder. Int J Clin Pract. 2021 Aug;75(8):e14330. doi: 10.1111/ijcp.14330. Epub 2021 May 26. |
| 33600233 | Derived | Nasser A, Kosheleff AR, Hull JT, Liranso T, Qin P, Busse GD, O'Neal W, Fava M, Faraone SV, Rubin J. Translating Attention-Deficit/Hyperactivity Disorder Rating Scale-5 and Weiss Functional Impairment Rating Scale-Parent Effectiveness Scores into Clinical Global Impressions Clinical Significance Levels in Four Randomized Clinical Trials of SPN-812 (Viloxazine Extended-Release) in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder. J Child Adolesc Psychopharmacol. 2021 Apr;31(3):214-226. doi: 10.1089/cap.2020.0148. Epub 2021 Feb 17. |
| FG002 | 400mg SPN-812 | 400mg SPN-812 oral capsule Treatment C: SPN-812 was administered once daily and compared to placebo |
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| COMPLETED |
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| NOT COMPLETED |
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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.
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| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | Placebo oral capsule Treatment A: Placebo will be administered once daily |
| BG001 | 200mg SPN-812 | 200mg SPN-812 oral capsule Treatment B: SPN-812 will be administered once daily and compared to placebo |
| BG002 | 400mg SPN-812 | 400mg SPN-812 oral capsule Treatment C: SPN-812 will be administered once daily and compared to placebo |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| ADHD-RS-5 Total Score | 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). | Mean | Standard Deviation | units on a scale |
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| ADHD-RS-5 Inattention | 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. | Mean | Standard Deviation | units on a scale |
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| ADHD-RS-5 Hyperactivity/Impulsivity | 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 HI Subscale score = 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. | Mean | Standard Deviation | units on a scale |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | Efficacy of SPN-812 Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) | The Primary Endpoint was the change from baseline in the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Total 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 Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) 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. | 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. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline and Week 6 (End of Study) |
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| Secondary | Effect of SPN-812 Assessed by Clinical Global Impression-Improvement (CGI-I) Scale | 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. | Posted | Mean | Standard Error | units on a scale | Week 6 (End of Study) |
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| Secondary | Effect of SPN-812 Assessed by Conners 3rd Edition - Parent Short Form (C3-PS) | 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. | Posted | Least Squares Mean | Standard Error | T-score | Baseline and Week 6 (End of Study) |
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| Secondary | Effect of SPN-812 Assessed by Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) | 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. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline and Week 6 (End of Study) |
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| Secondary | Effect of SPN-812 Assessed by 50% Responder Rate Per the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) | 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. | Posted | Number | percentage of subjects | Week 6 (End of Study) |
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| Secondary | Effect of SPN-812 Assessed by Stress Index for Parents of Adolescents (SIPA) | Another secondary endpoint was the change from baseline in the Stress Index for Parents of Adolescents (SIPA) Total score to Week 6 (End of Study). The SIPA is a 112-item screening/diagnostic instrument for parents of adolescents 11-19 years of age that identifies areas of stress in parent-adolescent interactions. Items 1-90 are rated on a 5-point Likert scale (where SD=Strongly Disagree, D=Disagree, NS=Not Sure, A=Agree, and SA=Strongly Agree) and yields a raw score for 3 Domains (Adolescent Domain, Parent Domain, and Adolescent-Parent Domain) that focus on a parent's perception of their child's personality and on the parent's characteristics and behaviors. The sum of the 3 Domain scores yields the Total (Parent Stress) score (range: 90-450; higher total scores indicate higher levels of stress). Lower change from baseline 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. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline and Week 6 (End of Study) |
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| Secondary | Effect of SPN-812 Assessed by the Hyperactivity/Impulsivity Subscale and the Inattention Subscale of the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) | 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. | Posted | Least Squares Mean | Standard Error | units on a scale | Baseline and Week 6 (End of Study) |
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| Secondary | Effect of SPN-812 Assessed by Conners 3rd Edition - Self Report Short Form (C3-SRS) | 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. | Posted | Least Squares Mean | Standard Error | T-score | Baseline and Week 6 (End of Study) |
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| Secondary | Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"] | 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. | Posted | Number | percentage of subjects | Week 1, Week 2, Week 3, Week 4, Week 5, Week 6 |
|
6 weeks
The number of subjects reported in each arm for Adverse Events table is based on the Safety Population (actual treatment arm); includes subjects who were randomized and took at least one dose of study medication. One subject was randomized to the 400mg SPN-812 arm (assigned treatment arm), but received 200mg SPN-812 during the trial (actual treatment arm). Therefore, the number of participants between SPN-812 arms will differ by 1 between the Participant Flow table and Adverse Events table.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo oral capsule Treatment A: Placebo will be administered once daily | 0 | 104 | 0 | 104 | 22 | 104 |
| EG001 | 200mg SPN-812 | 200mg SPN-812 oral capsule Treatment B: SPN-812 was administered once daily and compared to placebo | 0 | 99 | 2 | 99 | 39 | 99 |
| EG002 | 400mg SPN-812 | 400mg SPN-812 oral capsule Treatment C: SPN-812 was administered once daily and compared to placebo | 0 | 105 | 0 | 105 | 50 | 105 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Thermal burn | Injury, poisoning and procedural complications | MedDRA 20.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Somnolence | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 20.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 20.1 | Systematic Assessment |
|
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Joseph Hull, PhD, Associate Director Clinical Research | Supernus | 240-403-5324 | jhull@supernus.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Oct 18, 2018 | May 7, 2021 | SAP_001.pdf |
Not provided
| ID | Term |
|---|---|
| D001289 | Attention Deficit Disorder with Hyperactivity |
| ID | Term |
|---|---|
| D019958 | Attention Deficit and Disruptive Behavior Disorders |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
Not provided
Not provided
| 15 to 17 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| 0.0091 |
| Least Square Mean Difference |
| -5.1 |
| Standard Error of the Mean |
| 1.93 |
| 2-Sided |
| 95 |
| -8.9 |
| -1.3 |
| Superiority |
400mg SPN-812 oral capsule
Treatment C: SPN-812 was administered once daily and compared to placebo
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|
|
| 200mg SPN-812 |
200mg SPN-812 oral capsule Treatment B: SPN-812 was administered once daily and compared to placebo |
| OG002 | 400mg SPN-812 | 400mg SPN-812 oral capsule Treatment C: SPN-812 was administered once daily and compared to placebo |
|
|
|
| 200mg SPN-812 |
200mg SPN-812 oral capsule Treatment B: SPN-812 was administered once daily and compared to placebo |
| OG002 | 400mg SPN-812 | 400mg SPN-812 oral capsule Treatment C: SPN-812 was administered once daily and compared to placebo |
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|
200mg SPN-812 oral capsule
Treatment B: SPN-812 was administered once daily and compared to placebo
| OG002 | 400mg SPN-812 | 400mg SPN-812 oral capsule Treatment C: SPN-812 was administered once daily and compared to placebo |
|
|
|
| 200mg SPN-812 |
200mg SPN-812 oral capsule Treatment B: SPN-812 was administered once daily and compared to placebo |
| OG002 | 400mg SPN-812 | 400mg SPN-812 oral capsule Treatment C: SPN-812 was administered once daily and compared to placebo |
|
|
|
| 200mg SPN-812 |
200mg SPN-812 oral capsule Treatment B: SPN-812 was administered once daily and compared to placebo |
| OG002 | 400mg SPN-812 | 400mg SPN-812 oral capsule Treatment C: SPN-812 was administered once daily and compared to placebo |
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