A Phase I/IIa, Randomized, Double-Blind Study of the Safety and Efficacy of SPN-812 in Adults With ADHD

Study Overview
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Brief Summary
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This will be a randomized, double-blind, placebo-controlled, parallel group, safety and tolerability study in adults with ADHD. The target subjects are healthy male or female adults aged 18 to 64 years, inclusive, with a diagnosis of ADHD. A total of fifty subjects will be enrolled at approximately 5 sites in the US. Subjects will be randomized (1:1) to one of two treatment groups, SPN-812V or placebo.

Official Title
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A Phase I/IIa Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of the Safety and Efficacy of SPN-812 in Adults With Attention Deficit Hyperactivity Disorder (ADHD)

Conditions
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ADHD

Intervention / Treatment
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* Drug: SPN-812
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Able to provide informed consent prior to any study procedure being conducted. Capable and willing to comply with study procedures. Male or female aged 18 to 64, inclusive. Subjects with a current diagnosis of ADHD as confirmed by the Conners' Adult ADHD Diagnostic Interview for DSM-IV (CAADID) Clinical Global Impression - Severity (CGI-S) score of 4 or higher. On no treatment for ADHD or willing to be withdrawn from an ongoing treatment after a washout of at least 10 days. Body Mass Index (BMI) between 18.0 and 34.0 inclusive. Subject must be in general good health as determined by medical history, ECG, and other analysis that, in the judgment of the Investigator, would confirm the Subject's good health. Females of childbearing potential (FOCP) who, if sexually active, agree to use acceptable forms of contraception (including oral, transdermal, or implanted contraceptives; intrauterine device; female condom with spermicide; diaphragm with spermicide; cervical cap; abstinence; use of condom with spermicide by sexual partner or sterile [at least 6 months prior to SM administration] sexual partner) at least 14 days prior to start of study drug administration, throughout the study, and for 30 days following the last dose of SM. Postmenopausal females with amenorrhea for at least 2 years or females who are permanently sterilized (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy). Exclusion Criteria Current or past history of psychotic disorder or major depressive disorder with psychotic features. Presence of another primary DSM-IV-TR disorder. Suicidality, defined as either active suicidal plan/intent or active suicidal thoughts, in the 6 months before the Screening Visit or more than 1 lifetime suicide attempt. (The Columbia-Suicide Severity Rating Scales [C-SSRS] will be administered at each visit.) Substance or alcohol abuse/dependence within previous 6 months, or a positive urine drug screen at screening or baseline prior to first dose of study medication (SM). Any known or suspected significant medical or psychiatric illnesses that, in the judgment of the Investigator, may impair interpretation of study results or constitute a significant safety concern in the context of the clinical trial ECG abnormalities (clinically significant according to Investigator's opinion) or vital sign abnormalities (systolic blood pressure [SBP] <90 or >140 millimeters of mercury [mmHg], diastolic blood pressure [DBP] <40 or >90mmHg, or heart rate [HR] <40 or >100 beats per minute [BPM]) at screening. Clinically significant laboratory abnormalities; including presence of potential hepatic function impairment as shown by, but not limited to alanine aminotransferase (ALT/SGPT) values >2 times upper limit of normal (ULN), aspartate aminotransferase (AST/SGOT) > 2 times ULN, gamma-glutamyl transpeptidase (GGT) >3 times ULN, or total bilirubin >1.5 ULN . Medications, including health food supplements judged by the Investigator to be likely to have central nervous system activity (for example, St John's Wort, gingko leaf, and melatonin), are not permitted during the study. If the subject is taking the medication prior to study entry, there must be a 7 day washout period prior to first dose of SM. Lifetime history of tic disorder, Tourette's Disease, or organic brain disorder; or family history of Tourette's Disease. Current or lifetime history of hyperthyroidism unless treated and stable for at least 6 months. Participation in or plan to begin behavioral therapy during the study. Subject has a prior history of allergy or any significant adverse reaction (including rash) to study medication, or any of the product components. Females who are pregnant or lactating or are unwilling to use an acceptable form of contraception throughout the study. Difficulty swallowing whole capsules. History of seizures or risk factors for seizures (e.g., head trauma), not including febrile seizures. Use of an investigational drug or participation in an investigational study within 30 days prior to first dose of SM. Any reason which, in the opinion of the Investigator, would prevent the subject from participating in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SPN-812<br>viloxazine, oral, 300mg, tid, 6 weeks | Drug: SPN-812<br>* Viloxazine, oral, 300mg, tid, 6 weeks<br>* Other names: viloxazine;|
| Placebo Comparator: Placebo<br>placebo, oral, tid, 6weeks | Drug: Placebo<br>* Placebo, oral, tid, 6 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigator-rated Conners' Adult ADHD Rating Scales (CAARS) | Change from Baseline in the Investigator-rated Conners' Adult ADHD Rating Scales (CAARS) Total ADHD Symptom Score | At Baseline and at each study visit (V1-V8) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CGI-Improvement (CGI-I) Scale | Changes from Baseline in the CGI-Improvement (CGI-I) Scale At Baseline: CGI-Severity (CGI-S) | At each study visit (V1-V8) | 
| Self rated CAARS | Changes from Baseline in the Self rated CAARS Total ADHD Symptom Score | Baseline and at each study visit (V1-V8) |