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Evaluation of SPN-812 (Viloxazine Extended-release Capsule) High Dose in Children With ADHD

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ClinicalTrials.gov Identifier: NCT03247543
Recruitment Status : Completed
First Posted : August 11, 2017
Results First Posted : July 8, 2021
Last Update Posted : July 8, 2021
Sponsor:
Information provided by (Responsible Party):
Supernus Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE August 9, 2017
First Posted Date  ICMJE August 11, 2017
Results First Submitted Date  ICMJE May 24, 2021
Results First Posted Date  ICMJE July 8, 2021
Last Update Posted Date July 8, 2021
Actual Study Start Date  ICMJE October 31, 2017
Actual Primary Completion Date October 17, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 24, 2021)
Efficacy of SPN-812 Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) [ Time Frame: Baseline and Week 8 (End of Study) ]
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 8 (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 (none) to 3 (severe). 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 9, 2017)
Efficacy of SPN-812 ER assessed by ADHD-Rating Scale [ Time Frame: 8 weeks ]
Change from Baseline to End of Study in the ADHD-RS-V-total score
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 16, 2021)
  • Effect of SPN-812 Assessed by Clinical Global Impression-Improvement (CGI-I) Scale [ Time Frame: Week 8 (End of Study) ]
    The first Key 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" and 7 = "very much worse." Successful therapy is indicated by a lower overall score in subsequent testing.
  • Effect of SPN-812 Assessed by Conners 3 - Parent Short Form (C3PS) [ Time Frame: Baseline and Week 8 (End of Study) ]
    The second Key Secondary Endpoint was the change from baseline in the Conners 3rd Edition - Parent Short Form (C3PS) Composite T-score at Week 8 (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. 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 raw score(s). Raw score is converted to T-score to account for age (6-11 yrs or 12-18 yrs) and sex (male or female); the difference between T-score at Week 8 and the T-score at Baseline is then computed. A lower change from baseline T-score (<0) at Week 8 represent a better outcome.
  • Effect of SPN-812 Assessed by Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) [ Time Frame: Baseline and Week 8 (End of Study) ]
    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 8 (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). Lower change from baseline Total Average scores (<0) represent a better outcome.
  • Effect of SPN-812 Assessed by 50% Responder Rate Per the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) [ Time Frame: Week 8 (End of Study) ]
    An additional secondary endpoint was the percentage of responders at Week 8 (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 8 (End of Study). Values range from 0 to 100%. A higher percentage represents a greater number of responders.
  • Effect of SPN-812 Assessed by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) [ Time Frame: Baseline and Week 8 (End of Study) ]
    An additional secondary endpoint was the change from baseline in Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) Total score at Week 8 (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. Lower change from baseline total scores (<0) represent a better outcome.
  • 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) [ Time Frame: Baseline and Week 8 (End of Study) ]
    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 8 (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 (none) to 3 (severe). 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.
  • Effect of SPN-812 Assessed by Conners 3 - Self Report Short Form (C3-SRS) [ Time Frame: Baseline and Week 8 (End of Study) ]
    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 8 (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, validated in 8-18 years olds, is comprised of 41 items. 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 score is converted to T-score to account for age (8-11 yrs or 12-18 yrs) and sex (male or female); the difference between T-score at Week 8 and the T-score at Baseline is then computed. A lower change from baseline T-score (<0) at Week 8 represent a better outcome.
  • Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"] [ Time Frame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8 ]
    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".
Original Secondary Outcome Measures  ICMJE
 (submitted: August 9, 2017)
  • Effect of SPN-812 ER assessed by Conners 3 Rating Scale [ Time Frame: 8 weeks ]
    Change from Baseline to End-of Study in Conners Score
  • Effect of SPN-812 ER assessed by 30% Responder Rate [ Time Frame: 8 weeks ]
    Percentage of subjects with at least a 30% improvement in ADHD-RS-V Total score from Baseline to End of Study
  • Effect of SPN-812 ER assessed by ADHD Subscores [ Time Frame: 8 weeks ]
    Change from Baseline to End of Study in the hyperactivity/impulsivity and inattention subscales of ADHD-RS-V score
  • Effect of SPN-812 ER assessed by Weiss Functional Impairment Rating Scale- Parent report (WFIRS-P) [ Time Frame: 8 weeks ]
    Change from Baseline to End-of Study in WFIRS-P Score
  • Effect of SPN-812 ER assessed by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) [ Time Frame: 8 weeks ]
    Change from Baseline to End-of Study in PSI-4-SF Score
  • Effect of SPN-812 ER assessed by Clinical Global Impression-Severity of Illness and Improvement (CGI-S/I) Scale [ Time Frame: 8 weeks ]
    Change from Baseline to End of Study in CGI-S/I score
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of SPN-812 (Viloxazine Extended-release Capsule) High Dose in Children With ADHD
Official Title  ICMJE Evaluation of SPN-812 (Viloxazine Extended-release Capsule) 200 and 400 mg Efficacy and Safety in Children With ADHD - A Double-Blind, Placebo-Controlled, Pivotal Trial
Brief Summary This study will evaluate the efficacy and safety of high doses of SPN 812 in children with ADHD
Detailed Description 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 children 6-11 years old with ADHD.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
double-blind
Primary Purpose: Treatment
Condition  ICMJE ADHD
Intervention  ICMJE
  • Drug: Placebo
    Placebo was administered once daily
    Other Name: PBO
  • Drug: 200mg SPN-812
    200mg SPN-812 was administered once daily and compared to placebo
    Other Name: SPN-812
  • Drug: 400mg SPN-812
    400mg SPN-812 was administered once daily and compared to placebo
    Other Name: SPN-812
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Placebo, qd, oral capsule
    Intervention: Drug: Placebo
  • Active Comparator: 200mg SPN-812
    200mg SPN-812, qd, oral capsule
    Intervention: Drug: 200mg SPN-812
  • Active Comparator: 400mg SPN-812
    400mg SPN-812, qd, oral capsule
    Intervention: Drug: 400mg SPN-812
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 17, 2019)
313
Original Estimated Enrollment  ICMJE
 (submitted: August 9, 2017)
300
Actual Study Completion Date  ICMJE October 17, 2018
Actual Primary Completion Date October 17, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Healthy male or female subjects, 6-11 years of age, inclusive.
  2. 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).
  3. Attention Deficit/Hyperactivity Disorder Rating Scale-5, Home Version: Child, Investigator Administered and Scored (ADHD-RS-5) score of at least 28.
  4. CGI-S score of at least 4 at screening.
  5. Weight of at least 20 kg.
  6. Free of medication for the treatment of ADHD for at least one week prior to randomization and agreement to remain so throughout the study.
  7. Considered medically healthy by the Investigator via assessment of physical examination, medical history, clinical laboratory tests, vital signs, and electrocardiogram.
  8. Written informed consent obtained from the subject's parent or legal representative and informed assent from the subject, if applicable.
  9. 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:

    1. simultaneous use of male condom and intra-uterine contraceptive device placed at least four weeks prior to the first study drug administration
    2. surgically sterile male partner
    3. simultaneous use of male condom and diaphragm with spermicide
    4. established hormonal contraceptive

Exclusion Criteria:

  1. Current diagnosis of major psychiatric disorders. Subjects with Major Depressive Disorder are allowed in the study if the subject is free of episodes both currently and for the last six months.
  2. Current diagnosis of major neurological disorders. Subjects with seizures or a history of seizure disorder within the immediate family (siblings, parents), or a history of seizure-like events are excluded from the study.
  3. Current diagnosis of significant systemic disease.
  4. Evidence of suicidality (defined as either active suicidal plan/intent or active suicidal thoughts, or more than one lifetime suicide attempt) within the six months before Screening or at Screening.
  5. BMI greater than 95th percentile for the appropriate age and gender.
  6. History of an allergic reaction to viloxazine or related drugs.
  7. Any food allergy, intolerance, restriction or special diet that, in the opinion of the Investigator, could contraindicate the subject's participation in this study.
  8. Subjects who received any investigational drug within the longer of 30 days or 5 half-lives prior to Day 1 dosing of SM.
  9. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.
  10. Positive drug screen at the Screening Visit. 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 study, beginning at least one week prior to the Baseline Visit.
  11. Pregnancy or refusal to practice abstinence or acceptable birth control during the study (for female subjects of childbearing potential)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Years to 11 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03247543
Other Study ID Numbers  ICMJE 812P303
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Supernus Pharmaceuticals, Inc.
Study Sponsor  ICMJE Supernus Pharmaceuticals, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jonathan Rubin, MD Supernus Pharmaceuticals, Inc.
PRS Account Supernus Pharmaceuticals, Inc.
Verification Date August 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP