Clinical trial NCT03247543: Evaluation of SPN-812 (Viloxazine Extended-release Capsule) High Dose in Children With ADHD
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: ADHD
Lead sponsor: Supernus Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2017-08-11
Enrollment: 313
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Efficacy of SPN-812 Assessed by Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5)
timeFrame: Baseline and Week 8 (End of Study)
Secondary outcomes:
measure: Effect of SPN-812 Assessed by Clinical Global Impression-Improvement (CGI-I) Scale
timeFrame: Week 8 (End of Study)
measure: Effect of SPN-812 Assessed by Conners 3 - Parent Short Form (C3PS)
timeFrame: Baseline and Week 8 (End of Study)
measure: Effect of SPN-812 Assessed by Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P)
timeFrame: Baseline and Week 8 (End of Study)
measure: Effect of SPN-812 Assessed by 50% Responder Rate Per the Attention-Deficit/Hyperactivity Disorder Rating Scale, 5th Edition (ADHD-RS-5)
timeFrame: Week 8 (End of Study)
measure: Effect of SPN-812 Assessed by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
timeFrame: Baseline and Week 8 (End of Study)
measure: 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)
timeFrame: Baseline and Week 8 (End of Study)
measure: Effect of SPN-812 Assessed by Conners 3 - Self Report Short Form (C3-SRS)
timeFrame: Baseline and Week 8 (End of Study)
measure: Effect of SPN-812 Assessed by Categorical Clinical Global Impression - Improvement (CGI-I) [the Percentage of Subjects Who Were 'Improved"]
timeFrame: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7, Week 8
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: Alliance for Wellness
state: California
city: Lauderhill
country: United States
facility: Innovative Clinical Research, Inc
state: Florida
city: Orlando
country: United States
facility: APG Research, LLC
state: Florida
city: Tampa
country: United States
facility: University of South Florida- Dept. of Psychiatry and Neurosciences
state: Florida
city: Overland Park
country: United States
facility: Psychiatric Associates
state: Kansas
city: Oklahoma City
country: United States
facility: Paradigm Research Professionals
state: Oklahoma
city: Charleston
country: United States
facility: Carolina Clinical Trials, Inc.
state: South Carolina
city: Austin
country: United States
facility: BioBehavioral Research of Austin P.C.
state: Texas
city: Houston
country: United States
facility: Bayou City Research Corporation
state: Texas
city: Clinton
country: United States
facility: Ericksen Research & Development
state: Utah
Study officials:
affiliation: Supernus Pharmaceuticals, Inc.
name: Jonathan Rubin, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: Nasser A, Liranso T, Adewole T, Fry N, Hull JT, Chowdhry F, Busse GD, Melyan Z, Cutler AJ, Findling RL, Schwabe S. Once-Daily SPN-812 200 and 400 mg in the treatment of ADHD in School-aged Children: A Phase III Randomized, Controlled Trial. Clin Ther. 2021 Apr;43(4):684-700. doi: 10.1016/j.clinthera.2021.01.027. Epub 2021 Mar 6.
citation: 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.