Clinical trial NCT03247530: Evaluation of SPN-812 (Viloxazine Extended-release Capsule) Low Dose in Children With ADHD
Official title: Evaluation of SPN-812 (Viloxazine Extended-release Capsule) 100 and 200 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: 477
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 low doses of SPN-812 in children 6-11 years of age diagnosed 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 (ADHD) Rating Scale, 5th Edition (ADHD-RS-5)
timeFrame: Baseline and Week 6 (End of Study)
Secondary outcomes:
measure: Effect of SPN-812 Assessed by Clinical Global Impression-Improvement (CGI-I) Scale
timeFrame: Week 6 (End of Study)
measure: Effect of SPN-812 Assessed by Conners 3 - Parent Short Form (C3PS)
timeFrame: Baseline and Week 6 (End of Study)
measure: Effect of SPN-812 Assessed by Weiss Functional Impairment Rating Scale-Parent Report (WFIRS-P)
timeFrame: Baseline and Week 6 (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 6 (End of Study)
measure: Effect of SPN-812 Assessed by Parenting Stress Index, Fourth Edition, Short Form (PSI-4-SF)
timeFrame: Baseline and Week 6 (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 6 (End of Study)
measure: Effect of SPN-812 Assessed by Conners 3 - Self Report Short Form (C3-SRS)
timeFrame: Baseline and Week 6 (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
Other outcomes:
Locations:
city: Dothan
country: United States
facility: Harmonex Neuroscience Research
state: Alabama
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc.
state: Florida
city: Meridian
country: United States
facility: Advanced Clinical Research
state: Idaho
city: Rochester
country: United States
facility: Finger Lakes Clinical Research
state: New York
city: Houston
country: United States
facility: Houston Clinical Trials
state: Texas
city: The Woodlands
country: United States
facility: Family Psychiatry of the Woodlands
state: Texas
city: Orem
country: United States
facility: Aspen Clinical Research
state: Utah
Study officials:
affiliation: Supernus Pharmaceuticals, Inc.
name: Stefan Schwabe, 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, 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.
citation: Nasser A, Liranso T, Adewole T, Fry N, Hull JT, Chowdhry F, Busse GD, Cutler AJ, Jones NJ, Findling RL, Schwabe S. A Phase III, Randomized, Placebo-controlled Trial to Assess the Efficacy and Safety of Once-daily SPN-812 (Viloxazine Extended-release) in the Treatment of Attention-deficit/Hyperactivity Disorder in School-age Children. Clin Ther. 2020 Aug;42(8):1452-1466. doi: 10.1016/j.clinthera.2020.05.021. Epub 2020 Jul 25.