Open-label Safety and Efficacy of SPN-812 (Viloxazine Extended-release Capsule) in Adults With ADHD and Mood Symptoms

A Phase IV, Open-Label, Decentralized Clinical Trial to Evaluate the Efficacy and Safety of Qelbree® in Adults With Attention-Deficit/Hyperactivity Disorder and Mood Symptoms

Open label, flexible dose, decentralized clinical trial evaluating the efficacy and safety of SPN-812 in adults with ADHD and mood symptoms.

This is a Phase IV, open-label, flexible dose, decentralized clinical trial to evaluate the efficacy and safety of SPN-812 in adults with ADHD and mood symptoms. Adults 18 years and older with ADHD will be recruited, consented and screened for eligibility. Following the Screening Period (up to 4 weeks), eligible participants will be treated with Study medication for up to 14 weeks (Treatment Period). The total study duration is approximately 18 weeks, and there are up to 6 virtual study visits (or Televisits). All Televisits are conducted via an application downloaded to participant's mobile phone. There are up to 2 Televisits during the Screening period and 3 Televisits during the Treatment period. Subjects initiate SPN-812 dosing at 200 mg once daily during first week and then titrate up to 400 mg once daily during the second week. At the Investigator's discretion, based on subject's clinical response and tolerability, the dose of SPN-812 can be increased or decreased to optimal dose within the range between 200 and 600 mg once daily during the remaining Treatment period. Participants will answer questions during structured clinical interviews with an investigator during Televisits and complete additional questionnaires and scales via the mobile app.

Inclusion Criteria:

To be eligible for participation in this study, a participant must meet all of the following criteria:

1. Is male or female, ≥18 years of age.

2. Is willing and capable of providing and signing electronic informed consent.

3. Has a primary diagnosis of ADHD based on the Diagnostic and Statistical Manual of Mental Disorders; Fifth Edition, Text Revision (DSM-5-TR) as confirmed with the Mini-International Neuropsychiatric Interview for ADHD Studies (MINI-AS).

4. Has an AISRS Total score ≥24 at Screening.

5. Has a CGI-S score ≥3 at Screening.

6. Has a MADRS (SIGMA) Total score >22 at Screening and/or HAM-A (SIGH-A) Total score >22 at Screening.

7. If potential participant is a biological female, one of the following (a, b, or c) must be met:

   1. Has undergone menopause, defined as a biological female who reports amenorrhea for at least 12 consecutive months prior to providing informed consent.
   2. Is a non-pregnant Female of Childbearing Potential (FOCP) who is not seeking fertility treatment during the study and agrees to use one of the following acceptable birth control methods beginning 14 days prior to the first dose of study medication, throughout the study while taking study medication, and for 7 days following the last dose of study medication: i. Hormonal contraceptive; ii.Barrier method: simultaneous use of male condom and diaphragm or cervical cap with spermicidal foam/gel/film/cream/suppository.
   3. Has had bilateral tubal ligation, hysterectomy, bilateral oophorectomy (permanently sterilized) at least 6 months prior to providing informed consent.

8. If potential participant is a biological male, one of the following must be met:

   1. Is capable of having children and agrees to use 2 methods of contraception beginning 14 days prior to the first dose of study medication, throughout the study while taking study medication, and for 7 days following the last dose of study medication.
   2. Has had sterilization surgery (permanently sterilized) at least 6 months prior to providing informed consent.

9. Owns a functioning smartphone device, has access to an internet connection (Wi-Fi or data plan), is willing to download and use the study mobile app throughout the study, and is willing to have visual telemedicine appointments (televisits) at times designated in the study protocol.

Exclusion Criteria:

A participant who meets any of the following criteria will be excluded from participation in the study:

1. Has a history of substance use disorder (alcohol, opioids, etc.) within the last 6 months prior to providing informed consent with exception of nicotine and cannabis.

2. Is currently taking or has taken Qelbree for treatment of ADHD in the last 3 months or is currently taking another non-stimulant medication for treatment of ADHD, like atomoxetine (Strattera), Clonidine (Catapres, Kapvay) or Guanfacine (Tenex, Intuniv). Stimulant medications for ADHD and most medications for mood symptoms (symptoms of depression and/or anxiety) are allowed.

3. Is taking a prohibited concomitant medication per the Qelbree prescribing information.

4. Is a FOCP who is pregnant, nursing, sexually active with a male partner and not willing to use one of the acceptable birth control methods throughout the study and/or is seeking fertility treatment.

5. Has a history of moderate or severe head trauma or other neurological disorder or systemic medical disease that, in the Investigator's opinion, is likely to affect central nervous system functioning. This would include participants with:

   1. A current diagnosis of a major neurological disorder; or
   2. Seizures, seizure disorder or seizure-like events; or a history of seizure disorder within the immediate family (siblings, parents); or
   3. Encephalopathy

6. Has attempted suicide within the 6 months prior to the C-SSRS assessment at Screening, or is at significant risk of suicide, either in the opinion of the Investigator or defined as a "yes" to suicidal ideation questions 4 or 5 or answering "yes" to suicidal behavior on the C-SSRS within the 6 months prior to the C-SSRS assessment at Screening.

7. Is currently participating in another clinical trial or has participated in a clinical trial within the 60 days prior to providing informed consent.

8. Has any history of schizophrenia, schizoaffective disorder, or bipolar disorder, or has any other psychiatric disorders in the investigator's clinical judgement would interfere with their ability to participate in the study.

9. Has any unstable, clinically significant cardiovascular condition that in the investigator's clinical judgement would preclude their participating in the study.

10. Has any disease or taking any medication that could, in the Investigator's opinion, interfere with the assessments of safety, tolerability, or efficacy, or interfere with study conduct or interpretation of results.

11. History of unexplained loss of consciousness, unexplained syncope, unexplained irregular heartbeat or palpitations or near drowning with hospital admission.

12. In the Investigator's opinion, is unlikely to comply with the protocol or is unsuitable for any other reason.