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NCT03247543

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

Completed Phase 3 Results posted Last updated 8 July 2021
What this trial tests

Phase 3 trial testing Placebo in ADHD in 313 participants. Completed in 17 October 2018.

Timeline
31 October 2017
Primary endpoint
17 October 2018
17 October 2018

Quick facts

Lead sponsorSupernus Pharmaceuticals, Inc.
PhasePhase 3
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingquadruple
Primary purposetreatment
Enrollment313
Start date31 October 2017
Primary completion17 October 2018
Estimated completion17 October 2018
Sites10 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Supernus Pharmaceuticals, Inc. — full company profile →

Who can join

Adults 6 to 11, any sex, with ADHD. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Efficacy of SPN-812 Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Primary · 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: 0-5

GroupValue95% CI
Placebo-11.7± 1.48
200mg SPN-812-17.6± 1.43
400mg SPN-812-17.5± 1.52
Effect of SPN-812 Assessed by Clinical Global Impression-Improvement (CGI-I) Scale Secondary · 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.

GroupValue95% CI
Placebo3.1± 0.12
200mg SPN-8122.6± 0.12
400mg SPN-8122.6± 0.12
Effect of SPN-812 Assessed by Conners 3 - Parent Short Form (C3PS) Secondary · 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 freq

GroupValue95% CI
Placebo-5.3± 1.00
200mg SPN-812-9.1± 0.96
400mg SPN-812-7.8± 1.06
Effect of SPN-812 Assessed by Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P) Secondary · 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

GroupValue95% CI
Placebo-0.24± 0.042
200mg SPN-812-0.35± 0.041
400mg SPN-812-0.33± 0.044
Effect of SPN-812 Assessed by 50% Responder Rate Per the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5) Secondary · 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.

GroupValue95% CI
Placebo25.8
200mg SPN-81236.0
400mg SPN-81241.2
Effect of SPN-812 Assessed by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF) Secondary · 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 dysfunctio

GroupValue95% CI
Placebo-5.8± 1.95
200mg SPN-812-9.2± 1.88
400mg SPN-812-11.6± 2.01
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) Secondary · 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 fr

Hyperactivity/impulsivity subscale
GroupValue95% CI
Placebo-5.1± 0.78
200mg SPN-812-8.4± 0.76
400mg SPN-812-8.3± 0.81
Inattention subscale
GroupValue95% CI
Placebo-6.2± 0.77
200mg SPN-812-8.9± 0.74
400mg SPN-812-8.6± 0.80
Effect of SPN-812 Assessed by Conners 3 - Self Report Short Form (C3-SRS) Secondary · 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 \[very often, very frequently\] b

GroupValue95% CI
Placebo-3.3± 1.03
200mg SPN-812-3.9± 0.99
400mg SPN-812-5.4± 1.03
Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"] Secondary · 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".

Week 1
GroupValue95% CI
Placebo4.1
200mg SPN-81213.2
400mg SPN-81210.4
Week 2
GroupValue95% CI
Placebo14.5
200mg SPN-81225.8
400mg SPN-81224.9
Week 3
GroupValue95% CI
Placebo21.4
200mg SPN-81231.3
400mg SPN-81236.7
Week 4
GroupValue95% CI
Placebo26.6
200mg SPN-81241.9
400mg SPN-81237.4
Week 5
GroupValue95% CI
Placebo32.7
200mg SPN-81248.5
400mg SPN-81244.4
Week 6
GroupValue95% CI
Placebo30.3
200mg SPN-81251.0
400mg SPN-81249.5
Week 7
GroupValue95% CI
Placebo36.1
200mg SPN-81251.0
400mg SPN-81244.8
Week 8
GroupValue95% CI
Placebo35.5
200mg SPN-81247.3
400mg SPN-81247.8

Adverse events — posted to ClinicalTrials.gov

Time frame: 8 weeks. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Placebo
Serious: 0/103 (0%)
Deaths: 0/103
200mg SPN-812
Serious: 1/107 (1%)
Deaths: 0/107
400mg SPN-812
Serious: 2/100 (2%)
Deaths: 0/100

Serious adverse events (3 terms)

ReactionSystemPlacebo200mg SPN-812400mg SPN-812
SyncopeNervous system disorders
Suicidal behaviorPsychiatric disorders
Suicidal ideationPsychiatric disorders
Other adverse events (10 terms — click to expand)

ReactionSystemPlacebo200mg SPN-812400mg SPN-812
SomnolenceNervous system disorders
HeadacheNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
FatigueGeneral disorders
NasopharyngitisInfections and infestations
InsomniaPsychiatric disorders
VomitingGastrointestinal disorders
Abdominal pain upperGastrointestinal disorders
IrritabilityPsychiatric disorders
CoughRespiratory, thoracic and mediastinal disorders

Most-reported serious reactions: Syncope, Suicidal behavior, Suicidal ideation.

Data from ClinicalTrials.gov NCT03247543 adverse events section.

Sponsor's own description

This study will evaluate the efficacy and safety of high doses of SPN 812 in children with ADHD

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Once-Daily SPN-812 200 and 400 mg in the treatment of ADHD in School-aged Children: A Phase III Randomized, Controlled Trial.
    Nasser A, Liranso T, Adewole T, Fry N, et al · · 2021 · cited 36× · PMID 33750646 · DOI 10.1016/j.clinthera.2021.01.027
  2. A Phase 3 Placebo-Controlled Trial of Once-Daily 400-mg and 600-mg SPN-812 (Viloxazine Extended-Release) in Adolescents with ADHD.
    Nasser A, Liranso T, Adewole T, Fry N, et al · · 2021 · cited 31× · PMID 34092822
  3. Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Lisdexamfetamine in Healthy Adults.
    Faison SL, Fry N, Adewole T, Odebo O, et al · · 2021 · cited 20× · PMID 33587403 · DOI 10.1097/jcp.0000000000001361
  4. Pharmacokinetics of Coadministered Viloxazine Extended-Release (SPN-812) and Methylphenidate in Healthy Adults.
    Faison SL, Fry N, Adewole T, Odebo O, et al · · 2021 · cited 17× · PMID 33368026 · DOI 10.1007/s40261-020-00992-6
  5. Viloxazine: Pediatric First Approval.
    Lamb YN. · · 2021 · cited 15× · PMID 34036533 · DOI 10.1007/s40272-021-00453-3
  6. 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) i
    Nasser A, Kosheleff AR, Hull JT, Liranso T, et al · · 2021 · cited 14× · PMID 33600233 · DOI 10.1089/cap.2020.0148
  7. Population Pharmacokinetics of Viloxazine Extended-Release Capsules in Pediatric Subjects With Attention Deficit/Hyperactivity Disorder.
    Nasser A, Gomeni R, Wang Z, Kosheleff AR, et al · · 2021 · cited 13× · PMID 34269426 · DOI 10.1002/jcph.1940
  8. The Effect of Viloxazine Extended-Release Capsules on Functional Impairments Associated with Attention-Deficit/Hyperactivity Disorder (ADHD) in Children and Adolescents in Four Phase 3 Placebo-Controlled Trials.
    Nasser A, Hull JT, Liranso T, Busse GD, et al · · 2021 · cited 13× · PMID 34113106 · DOI 10.2147/ndt.s312011

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03247543.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing