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
Phase: PHASE4
Conditions: Attention-Deficit/Hyperactivity Disorder
Sponsor: Supernus Pharmaceuticals, Inc.

Supernus Pharmaceuticals, Inc. 
CONFIDENTIAL 
25Nov2024 
812P413 
 
Version 2.0 
 
This document is confidential. It contains proprietary information of Supernus® Pharmaceuticals, Inc. Any 
viewing or disclosure of such information that is not authorized in writing by the Sponsor is strictly prohibited. 
Such information may be used solely for the purpose of reviewing or performing this study. 
COVER PAGE - PROTOCOL 
 
 
 
 
 
 
 
 
Protocol Number: 
812P413 
Title: 
A Phase IV, Open-label, Decentralized Clinical Trial to Evaluate 
the Efficacy and Safety of Qelbree® in Adults with Attention-
Deficit/Hyperactivity Disorder (ADHD) and Mood Symptoms 
Sponsor: 
Supernus Pharmaceuticals, Inc. 
9715 Key West Avenue 
Rockville, MD 20850 
United States 
Phone: (301) 838-2500 
Fax: (240) 403-0065 
Protocol Version: 
2.0 
Date: 
25Nov2024 
NCT: 
NCT06185985 

           
 
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PROTOCOL 
A PHASE IV, OPEN-LABEL, DECENTRALIZED CLINICAL TRIAL TO EVALUATE THE 
EFFICACY AND SAFETY OF QELBREE® IN ADULTS WITH ATTENTION-
DEFICIT/HYPERACTIVITY DISORDER (ADHD) AND MOOD SYMPTOMS 
Protocol No.: 
  
812P413 
Test Article: 
 
Qelbree® (viloxazine extended-release capsules; SPN-812) 
Sponsor: 
  
Supernus Pharmaceuticals, Inc. 
 
  
9715 Key West Avenue, Rockville, MD 20850 
 
  
United States 
Sponsor Representative: 
 
  
 
  
 
  
 
  
 
  
Clinical Research 
 
Organization (CRO) :  
 
  
 
  
Phase of Study: 
  
Phase IV 
Study Design: 
  
Open label, decentralized clinical trial 
Country of Implementation: United States 
 
 

           
 
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INVESTIGATOR SIGNATURE PAGE 
Protocol Number: 812P413 
Version: 2.0 
Date: 25-Nov-2024 
 
INVESTIGATOR’S SIGNATURE 
I have read the protocol specified above and agree to participate in and comply with the 
procedures, as outlined herein for the conduct of this clinical trial. I also agree to comply with 
the applicable US Food and Drug Administration (FDA) regulations and Institutional Review 
Board (IRB) requirements for testing on human subjects. I agree to ensure that the 
requirements for obtaining informed consent are met. 
 
_______________________________________________________ 
______________ 
Investigator’s Signature 
 
 
 
 
 
          Date 
 
 
_______________________________________________________ 
Printed Name 
 
 
 

           
 
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DOCUMENT HISTORY 
Protocol 
Approval Date (Version) 
Amendment 01 
See Sponsor’s Protocol Approval Page (Version 2.0) 
Original  
10 Oct 2023 (Version 1.0) 
 
 
 

           
 
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SPONSOR’S PROTOCOL APPROVAL PAGE 
Protocol Number: 812P413 
Version: 2.0 
Date: 25-Nov-2024 
 
I have read the protocol specified above and agree to comply with the procedures, as outlined 
herein for the conduct of this clinical trial. The signature below indicates the sponsor’s approval 
of this protocol. 
 
 

           
 
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Contents 
1. 
LIST OF ABBREVIATIONS ................................................................................... 8 
2. 
PROTOCOL SYNOPSIS ..................................................................................... 10 
3. 
INTRODUCTION AND BACKGROUND............................................................... 15 
3.1 
Study Rationale.................................................................................................................. 15 
3.2 
Background ....................................................................................................................... 15 
3.2.1 
ADHD and Mood Symptoms ............................................................................................................ 15 
3.2.2 
Adult ADHD Qelbree Clinical Trial Findings ................................................................................. 17 
3.3 
Risk/Benefit Assessment ................................................................................................... 18 
3.3.1 
Known Potential Risks ........................................................................................................................ 18 
3.3.2 
Known Potential Benefits .................................................................................................................. 19 
3.3.3 
Assessment of Potential Risks and Benefits ................................................................................... 19 
4. 
STUDY OBJECTIVES AND ENDPOINTS.............................................................. 20 
5. 
RECRUITMENT AND PRE-SCREENING ............................................................... 23 
6. 
STUDY DESIGN ................................................................................................ 24 
6.1 
Screening Period ............................................................................................................... 24 
6.1.1 
Televisit #1a: ........................................................................................................................................ 24 
6.1.2 
Televisit #1b:........................................................................................................................................ 25 
6.2 
Treatment Period .............................................................................................................. 25 
6.3 
End of Study ...................................................................................................................... 26 
6.4 
Safety Follow-up (SF) Televisit .......................................................................................... 27 
7. 
STUDY POPULATION ....................................................................................... 30 
7.1 
Inclusion Criteria ............................................................................................................... 30 
7.2 
Exclusion Criteria............................................................................................................... 31 
7.3 
Screen Failures .................................................................................................................. 32 
7.4 
Recruitment and Retention ............................................................................................... 32 
8. 
STUDY TREATMENT ......................................................................................... 32 
8.1 
Study Treatment Description ............................................................................................ 32 
8.2 
Study Treatment Administration ...................................................................................... 32 
8.2.1 
Study Medication ................................................................................................................................ 32 
8.2.2 
Dosing ................................................................................................................................................... 32 
8.2.3 
Mode of Administration .................................................................................................................... 33 
8.3 
Study Product Preparation/Handling/Storage/Accountability ....................................... 33 

           
 
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8.4 
Concomitant Diets, Treatments, and Medications .......................................................... 33 
8.4.1 
Contraindications ............................................................................................................................... 33 
9. 
STUDY ASSESSMENTS AND PROCEDURES ....................................................... 34 
9.1 
Screening Assessments .................................................................................................... 34 
9.1.1 
Psychiatric Diagnostic Instruments .................................................................................................. 34 
9.1.1.1 
Mini-International Neuropsychiatric Interview for ADHD Studies (MINI-AS) .......................... 34 
9.2 
Efficacy Assessments......................................................................................................... 35 
9.2.1 
Clinician-Rated Outcomes (ClinROs) .............................................................................................. 35 
9.2.1.1 
Adult ADHD Investigator Symptom Rating Scale (AISRS)........................................................... 35 
9.2.1.2 
Clinical Global Impressions of Severity/Change (CGI-S/C) Scales ........................................... 35 
9.2.1.3 
Montgomery–Åsberg Depression Rating Scale (MADRS) .......................................................... 36 
9.2.1.4 
Hamilton Anxiety Rating Scale (HAM-A)......................................................................................... 36 
9.2.2 
Patient-Reported Outcomes (PROs) ............................................................................................... 37 
9.2.2.1 
Adult ADHD Self-Report Scale v1.1 Symptom Checklist (ASRSv1.1-SC) ................................. 37 
9.2.2.2 
Patient Health Questionnaire (PHQ-8) ............................................................................................ 38 
9.2.2.3 
General Anxiety Disorder-7 item (GAD-7) Scale .......................................................................... 38 
9.2.2.4 
Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A)............................. 38 
9.2.2.5 
Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) ............... 40 
9.2.2.6 
Pittsburgh Sleep Quality Index (PSQI) ............................................................................................ 40 
9.3 
Questionnaires .................................................................................................................. 41 
9.3.1 
Reproductive/Menstrual Cycle History (RMCH) Questionnaire ................................................. 41 
9.4 
Safety Assessments ........................................................................................................... 41 
9.4.1 
Adverse Events .................................................................................................................................... 41 
9.4.2 
Blood Pressure/Pulse Rate and Weight.......................................................................................... 41 
9.4.3 
Columbia-Suicide Severity Rating Scale (C-SSRS) ........................................................................ 41 
9.5 
Adverse Events .................................................................................................................. 42 
9.5.1 
Definition of Adverse Events ............................................................................................................ 42 
9.5.2 
Definition of Serious Adverse Events .............................................................................................. 42 
9.5.3 
Adverse Event Reporting .................................................................................................................. 42 
9.5.4 
Serious Adverse Event Reporting .................................................................................................... 43 
9.5.5 
Adverse Event Severity and Causality Assessments .................................................................... 43 
9.5.6 
Serious Adverse Event Follow-Up ................................................................................................... 45 
9.5.7 
Pregnancy Reporting ......................................................................................................................... 45 
10. 
STUDY COMPLETION AND DISCONTINUATION................................................ 45 
10.1 
Study Completion.......................................................................................................... 45 
10.2 
Study Discontinuation ................................................................................................... 46 
10.3 
Lost to Follow-up ........................................................................................................... 46 
11. 
DATA MANAGEMENT ...................................................................................... 47 
11.1 
Data Collection .............................................................................................................. 47 

           
 
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11.2 
Data Handling ................................................................................................................ 47 
11.3 
Data Entry....................................................................................................................... 47 
11.4 
Computerized Logical Checks ...................................................................................... 47 
11.5 
Audit Trail ....................................................................................................................... 48 
12. 
STATISTICAL METHODS ................................................................................... 48 
12.1 
General Considerations ................................................................................................ 48 
12.2 
Populations for Analyses ............................................................................................... 48 
12.3 
Determination of Sample size ....................................................................................... 48 
12.4 
Patient Disposition......................................................................................................... 49 
12.5 
Demographics and Baseline Analysis .......................................................................... 49 
12.6 
Study Medication Exposure and Compliance.............................................................. 49 
12.7 
Concomitant Medications ............................................................................................. 49 
12.8 
Efficacy Analysis ............................................................................................................. 49 
12.8.1 
Primary Endpoint(s) ............................................................................................................................ 49 
12.8.2 
Secondary Endpoint(s) ...................................................................................................................... 49 
12.9 
Safety Analysis ............................................................................................................... 50 
12.10 
Exploratory Analysis ...................................................................................................... 50 
13. 
QUALITY CONTROL AND ASSURANCE ............................................................. 51 
13.1 
Acceptability of Case Report Forms (Source Documents) .......................................... 51 
13.2 
Modification of Protocol ................................................................................................ 51 
13.3 
Reporting Protocol Deviations ...................................................................................... 52 
13.4 
Monitoring ..................................................................................................................... 52 
13.5 
Audits and Inspections .................................................................................................. 52 
14. 
ETHICS AND REGULATORY REQUIREMENTS .................................................... 53 
14.1 
Institutional Review Board/Independent Ethics Committee ....................................... 53 
14.2 
Investigator Responsibilities ......................................................................................... 53 
14.3 
Informed Consent Process ............................................................................................ 53 
15. 
STUDY CLOSURE.............................................................................................. 54 
16. 
PUBLICATION PLAN ......................................................................................... 54 
17. 
REFERENCES ................................................................................................... 56 
 

           
 
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mg 
Milligrams  
MI 
Metacognition Index 
MINI-AS 
Mini-International Neuropsychiatric Interview for ADHD Studies 
NRI 
Norepinephrine reuptake inhibitor 
OCD 
Obsessive compulsive disorder  
PHQ-8 
Patient Health Questionnaire-8 item 
PI 
Principal Investigator 
PRO 
Patient-reported outcome 
PSQI 
Pittsburgh Sleep Quality Index 
PT 
Preferred Term 
PTSD 
Post-traumatic stress disorder 
QA 
Quality Assurance 
QC 
Quality Control 
OCD 
Obsessive Compulsive Disorder 
QD 
Once a day 
RMCH 
Reproductive/Menstrual Cycle History Questionnaire 
SAE 
Serious Adverse Event 
SIGH-A 
Structured Interview Guide for the Hamilton Anxiety Scale 
SIGMA 
Structured Interview Guide for the Montgomery-Åsberg Depression Rating 
Scale 
SM 
Study medication 
SOC 
System Organ Class  
SOE 
Schedule of Events 
SOP 
Standard Operating Procedure 
Sub-I 
Sub-Investigator 
TEAE 
Treatment-emergent Adverse Event 
UAP 
Unanticipated problems 
US 
United States 
WPAI:SHP 
Work Productivity and Activity Impairment: Specific Health Problem 
Questionnaire 
 
 
 

           
 
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2. Protocol Synopsis 
Title 
A Phase IV, Open-label, Decentralized Clinical Trial to Evaluate the Efficacy and Safety of 
Qelbree in Adults with Attention-Deficit/Hyperactivity Disorder (ADHD) and Mood 
Symptoms 
Study Description: 
This is a Phase IV, open-label, decentralized clinical trial to evaluate the efficacy and safety 
of Qelbree in adults with ADHD and mood symptoms. Adults 18 years and older will be 
recruited into this study. Participants will be recruited using digital and social media 
advertising, and referrals from physicians' existing patient pool. Individuals who are pre-
qualified will be sent an email invitation to download the study app and contacted to 
schedule a screening televisit. Once eligibility is confirmed and participants are enrolled, 
study medication will be shipped. The treatment period will last for up to a total of 14 
weeks. Participants will be assessed for compliance and specific outcomes during the 
treatment period 
Study Objectives  
Primary Efficacy Objective 
The primary objective of this study is to evaluate the efficacy of Qelbree as a monotherapy 
and/or as an adjunctive therapy for ADHD symptoms in adults with ADHD and comorbid 
mood symptoms as measured by the clinician-rated ADHD Investigator Symptom Rating 
Scale (AISRS). 
Secondary Efficacy Objectives 
The secondary objectives of this study are to evaluate the effect of Qelbree as a 
monotherapy and/or as an adjunctive therapy in adults with ADHD and comorbid mood 
symptoms on:  
• Inattention and Hyperactivity/Impulsivity symptoms as measured by the clinician-rated 
AISRS. 
• ADHD symptoms as measured by self-rated Adult ADHD Self-Report Scale Symptoms 
Checklist (ASRSv1.1-SC). 
• Inattention and Hyperactivity/Impulsivity symptoms as measured by the self-rated 
ASRSv1.1-SC 
• Global severity of ADHD symptoms as measured by Clinical Global Impression of 
Severity (CGI-S) scale 
• Global change of ADHD symptoms as measured by the Clinical Global Impression of 
Change (CGI-C) scale 
• Depressive symptoms as measured by the clinician-rated Structured Interview Guide for 
the Montgomery and Åsberg Depression Rating Scale (SIGMA) and by the self-rated 
Patient Health Questionnaire 8-Item (PHQ-8) 

           
 
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• Anxiety symptoms as measured by the clinician-rated Structured Interview Guide for the 
Hamilton Anxiety Scale (SIGH-A) and the self-rated General Anxiety Disorder 7-Item 
(GAD-7) 
• Executive Function as measured by the Behavior Rating Inventory of Executive Function–
Adult Version (BRIEF-A), Self-Report 
• Aspects of functioning in daily life (work productivity and regular activities) as measured 
by the Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) 
Questionnaire 
• Sleep as measured by the self-rated Pittsburgh Sleep Quality Index (PSQI) 
Secondary Safety Objective 
To evaluate the safety of Qelbree as a monotherapy and/or as an adjunctive therapy in 
adults with ADHD and comorbid mood symptoms. 
Exploratory Objective 
Study Endpoints  
Primary Efficacy Endpoint 
• 
Change from baseline in AISRS Total score by visit 
Secondary Efficacy Endpoints 
• 
Change from baseline in AISRS Inattention and Hyperactivity/Impulsivity Subscale 
scores by visit 
• 
Change from baseline in ASRSv1.1-SC Total score by visit 
• 
Change from baseline in ASRSv1.1-SC Inattention and Hyperactivity/Impulsivity 
Subscale scores by visit 
• 
Change from baseline in CGI-S score by visit 
• 
CGI-C score by visit 
• 
Change from baseline in MADRS Total Score at Week 14/EOS 
• 
Change from baseline in PHQ-8 Total Score by visit 
• 
Change from baseline in HAM-A Total Score at Week 14/EOS 
• 
Change from baseline in GAD-7 Total Score by visit 
• 
Change from baseline at Week 14/EOS in BRIEF-A T-score for:  
i. Global Executive Composite (GEC)  
ii. Behavioral Regulation Index (BRI) 
iii. Metacognition Index (MI) 

           
 
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• 
Change from baseline in the WPAI:SHP: 
o absenteeism percentage by visit 
o presenteeism percentage by visit 
o work productivity percentage by visit 
o regular activity percentage by visit 
• 
Change from baseline at Week 14/EOS in the PSQI global score  
Secondary Safety Endpoints 
• 
Adverse events (AEs)  
• 
Change from baseline in blood pressure, pulse rate, and weight  
• 
Suicidality using the Columbia Suicide Severity Rating Scale (C-SSRS) 
Exploratory Endpoints 
Study Population 
Adults ≥18 years of age with ADHD (primary diagnosis) and Mood Symptoms will be 
screened for eligibility. Up to 750 adults will be enrolled (defined as having signed ICF and 
taken at least 1 dose of Qelbree). Based on a dropout rate of 33%, up to 500 participants 
will complete the study. 
Study Sites  
Single, decentralized site in the United States  
Study Duration 
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 between 
informed consent and the end of the Treatment Period is approximately 18 weeks. 
Description of Study Treatment  
Study Medication (SM): Qelbree [viloxazine extended-release capsules; SPN-812] 100 mg, 
150 mg, and 200 mg capsules. 
Dosing: 200 mg once daily (QD) during Week 1; and 400 mg QD Week 2 onwards. Dosage 
may be adjusted/titrated in increments of up to 200 mg weekly to the maximum 
recommended dosage of 600 mg once daily, depending on response and tolerability.  
Reference Therapy: None 
Route of administration: Orally, with or without food. Can be swallowed intact (whole) or 
contents of the capsule can be sprinkled over a teaspoonful of pudding/applesauce that is 
consumed entirely. See Section 8.2 for further details. 

           
 
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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: 
a. Has undergone menopause, defined as a biological female who reports amenorrhea 
for at least 12 consecutive months prior to providing informed consent.  
b. 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 
c. 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: 
a. 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.  
b. 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. 

           
 
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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: 
a. A current diagnosis of a major neurological disorder; or 
b. Seizures, seizure disorder or seizure-like events; or a history of seizure disorder within 
the immediate family (siblings, parents); or 
c. 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. 

           
 
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3. Introduction and Background 
3.1 
Study Rationale 
Attention-deficit/hyperactivity disorder (ADHD) is one of the most common childhood 
disorders that can continue through to adolescence and into adulthood. Symptoms include 
difficulty staying focused and paying attention, difficulty controlling behavior, and 
hyperactivity (over-activity). The overall prevalence of ADHD in adults is between 2.5% and 
6.7% with it being more common in men than women (Abdelnour et al., 2022). A majority of 
adults with ADHD also experience psychiatric comorbidities, particularly mood disorder 
symptoms, like depression and anxiety (Kessler et al., 2006; Kolar et al., 2008). Medication 
treatment for both ADHD and any comorbid psychiatric disorders can be challenging.  
While there is no cure for ADHD, available treatments aim to reduce symptoms and improve 
functioning. Qelbree, viloxazine extended-release capsules (SPN-812), is a selective 
norepinephrine reuptake inhibitor indicated for the treatment of ADHD in adults and 
pediatric patients 6 years and older. It is the first novel, non-stimulant option FDA-approved 
for adults with ADHD in the last twenty years. 
The active substance in Qelbree is viloxazine, whose mechanism of action is still not fully 
understood. Viloxazine was previously marketed in several European countries as an 
antidepressant in an immediate-release (IR) product (Findling et al., 2021). The efficacy and 
safety of Qelbree was evaluated for the treatment of ADHD in children (Johnson et al., 2020; 
Nasser et al., 2020; Nasser et al., 2021a), in adolescents (Nasser et al., 2021b; Nasser et al., 
2021c) and in adults (Nasser et al., 2022). In these trials including the adult trial, participants 
were excluded for other psychiatric disorders, including depression and anxiety. 
To date no evaluation of Qelbree has been conducted in adults with ADHD and mood 
symptoms, as well as those receiving concurrent medication treatment for mood symptoms. 
This study will evaluate the efficacy and safety of Qelbree in adults with ADHD and mood 
symptoms in an open-label, real-world setting. 
3.2 
Background 
3.2.1 
ADHD and Mood Symptoms 
ADHD, a childhood-onset neurodevelopmental condition, is a frequent and disabling 
condition in adults (Magnin and Maurs, 2017). In adulthood, the clinical presentation, as in 
childhood, involves the symptom triad of inattention, hyperactivity, and impulsivity (Weibel et 
al., 2020). However, in adults, hyperactivity is more often internalized, symptoms of 
inattention may be masked by anxiety symptoms or obsessive-like compensation strategies 
(Weibel et al., 2020).  
Several studies in adults with ADHD have reported its association with comorbid depression, 
anxiety, bipolar disorder, and substance use disorder. The National Comorbid Survey found 
that adults with ADHD are three times more likely to develop major depressive disorder 
(MDD), six times more likely to develop dysthymia, and more than four times more likely to 
have any mood disorder (Kessler et al., 2006). These comorbidities present important clinical 

           
 
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challenges since their co-occurrence results in greater disease burden and more severe 
illness courses than ADHD or mood and anxiety disorders alone (Katzman et al., 2017). 
Furthermore, the World Federation of ADHD International Consensus Statement reports that 
many large epidemiologic and clinical studies show that ADHD often co-occurs with other 
psychiatric disorders, especially depression, bipolar disorder, autism spectrum disorders, 
anxiety disorders, oppositional defiant disorder, conduct disorder, eating disorders, and 
substance use disorders; and their presence does not rule out a diagnosis of ADHD (Faraone 
et al., 2021).  
An important treatment consideration is the potential for the effective treatment of ADHD to 
improve functional outcomes in people with comorbid conditions. For instance, many studies 
have reported improvements in comorbid psychiatric symptoms when ADHD is effectively 
treated. Atomoxetine has been associated with improvements in both ADHD and comorbid 
anxiety and depressive symptoms; and the efficacy of co-administration of SSRIs or SNRIs 
with stimulants on functional outcomes in ADHD with comorbid anxiety or depressive 
symptoms (Katzman et al., 2017).  
Furthermore, data suggests that early and optimal treatment of ADHD has the potential to 
alter the trajectory of psychiatric morbidity by preventing the emergence of psychiatric 
comorbidities such as mood and anxiety disorders or substance use disorders (Katzman et 
al., 2017). In a 10-year longitudinal study of male youths with ADHD, Biederman et al., (2009) 
found that those who were treated with stimulants had a significantly lower risk of developing 
comorbid depressive and anxiety disorders as adults and were also significantly less likely to 
have impaired functional outcomes, than those who were not treated (Katzman et al., 2017). 
The burden of associated mood disorders with ADHD in adulthood affects multiple areas of a 
person’s life, and may result in serious functional impairment, in various domains, leading to 
academic, social, vocational, and familial consequences (Weibel et al., 2020). Furthermore, 
adults with ADHD have shown lower self-esteem, greater sleep disturbances, and an 
increased risk of mortality and comorbidities such as depression, anxiety, and substance use 
disorders compared with non-ADHD adults (Weibel et al., 2020). Accordingly, the cumulative 
negative consequences of living with ADHD in adulthood can substantially impact an 
individual’s social, emotional, educational, professional, and economic well-being (Weibel et 
al., 2020). The considerable disability and the poorer quality of life among adults with ADHD, 
therefore, warrants optimal evaluation and management (Weibel et al., 2020).  
Management often employs common psychological approaches such as psycho-education 
and cognitive-behavioral therapy with a specific focus on emotional regulation (Weibel et al., 
2020). Current pharmacological treatments for ADHD include stimulant and nonstimulant 
medications (Groom and Cortese, 2022). Psychostimulants are commonly used to treat 
ADHD and although their safety and tolerance are satisfactory, their long-term clinical benefit 
is still under discussion (Weibel et al., 2020; Groom and Cortese, 2022). Alternatively, when 
response or tolerability to psychostimulants is poor, or when certain comorbid disorders are 
present, nonstimulants stand to play an important role in the management of ADHD (Weibel 
et al., 2020; Groom and Cortese, 2022). 

           
 
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3.2.2 
Adult ADHD Qelbree Clinical Trial Findings 
The efficacy and safety of Qelbree for the treatment of ADHD in adults was assessed in a 
Phase III, multicenter, randomized, double-blind, placebo-controlled, parallel group, two-
arm, 6-week trial (Study 812P306) (Qelbree® Prescribing Information [PI]; Nasser et al., 2022). 
Eligible adults aged 18 to 65 years were randomized 1:1 to viloxazine extended-release (ER) 
(flexible dose of 200–600 mg/day) or matched placebo. Participants took Qelbree 200 mg or 
matching placebo QD during Week 1 and Qelbree 400 mg or matching placebo QD during 
Week 2. Based on efficacy and tolerability, the Investigator could adjust dose by 200mg/day 
per week at Week 3 and Week 4 visits. Treatments were administered as a once daily single 
dose. The primary efficacy endpoint was the change from baseline in the AISRS Total score at 
end of study (EOS; Week 6). The key secondary endpoint was the change from baseline in 
the CGI-S score at EOS. Other secondary measures included CGI-I score at EOS and change 
from baseline at EOS in the AISRS inattention and hyperactivity/impulsivity subscale scores, 
BRIEF-A T-scores, and GAD-7 total score. 
A total of 374 adults were randomized, 372 were dosed and 267 completed the study. At end 
of study, the mean viloxazine ER dose was 504 mg. In this study (Nasser et al., 2022): 
• 
The reduction in the change from baseline AISRS Total score (least-square means ± 
standard error) at EOS was greater in participants treated with viloxazine ER (−15.5 ± 
0.91; n=175) compared with placebo (−11.7 ± 0.90; n=179), and the difference (-3.7 ± 
1.28) was statistically significant (p = 0.0040).  
• 
The reduction in the change from baseline CGI-S score at EOS was also greater in 
participants treated with viloxazine ER (−1.4 ± 0.10; n=175) compared with placebo 
(−1.0 ± 0.10; n=179), and the difference (-0.4 ± 0.14) was statistically significant (p = 
0.0023).  
• 
The viloxazine ER group demonstrated significantly greater improvements (mean 
difference [lower95%CI, upper95%CI]) in the AISRS Inattention (−2.5 [−4.0, −0.9]; p = 
0.0015) and Hyperactivity/Impulsivity (−1.4 [−2.7, −0.1]; p = 0.0380) subscales, the 
CGI-I (−0.3 [−0.6, -0.1]; p = 0.0076), and the BRIEF-A Global Executive Composite 
(−2.4 [−4.8, 0.0]; p = 0.0468) and Metacognition Index (−3.3 [−5.9, −0.8]; p = 0.0100).  
• 
Analysis of categorical secondary endpoints revealed that the AISRS 30% response rate 
(defined as the percent of participants with a 30% or more reduction in AISRS Total 
Score) at Week 6 was significantly higher in the viloxazine ER group compared with 
placebo (12.4 [0.6, 23.8]; p = 0.0395); all other comparisons were not significant. 
In terms of safety, the most common adverse reactions of Qelbree (occurring at ≥5% and at 
least twice the placebo rate) were insomnia, headache, somnolence, fatigue, nausea, 
decreased appetite, dry mouth, and constipation (Qelbree PI). Adverse events (AEs) leading 
to discontinuation of Qelbree treatment were fatigue, insomnia, constipation, and headache. 
Adverse reactions that occurred in at least 2% of patients treated with Qelbree (n=189) and 
more frequently in Qelbree-treated patients than in placebo-treated patients were: insomnia 
(23% vs 7%), headache (17% vs 7%), nausea (12% vs 3%), dry mouth (10% vs 2%), fatigue 
(12% vs 3%), decreased appetite (10% vs 3%), and tachycardia (4% vs 1%).  

           
 
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3.3 
Risk/Benefit Assessment 
3.3.1 
Known Potential Risks 
The safety of Qelbree has been evaluated in 189 adult participants (18 to 60 years of age) 
with ADHD exposed to one or more doses ranging from 200 mg to 600 mg QD in a short-
term (6 week), randomized, double-blind, placebo-controlled trial (Study 812P306). 
Approximately 9% of the 189 participants receiving Qelbree discontinued treatment due to 
an adverse reaction. The adverse reactions most commonly associated with discontinuation 
of Qelbree were fatigue (n=4), insomnia (n=3), constipation (n=3), and headache (n=2). The 
most commonly reported adverse reactions (occurring at ≥5% and at least twice the placebo 
rate of Qelbree) were insomnia, headache, somnolence, fatigue, nausea, decreased appetite, 
dry mouth, and constipation (Qelbree PI).  
Adverse Events of concern include (Qelbree PI): 
• 
Suicidal Thoughts and Behavior: Among 189 adults treated with Qelbree, a total of 
three participants (1.6%) reported suicidal ideation on the C-SSRS, versus 0 of 183 
adults treated with placebo. No adults treated with either Qelbree or placebo 
reported suicidal behavior on the C-SSRS in the study. No attempted or completed 
suicides occurred in the trial. Participants treated with Qelbree had higher rates of 
insomnia and irritability. Although a causal link between the emergence of insomnia 
and irritability and the emergence of suicidal impulses has not been established, there 
is a concern that these and other symptoms such as depressed mood, anxiety, 
agitation, akathisia, mania, hypomania, panic attacks, impulsive behavior, and 
aggression may represent precursors to emerging suicidal ideation or behavior.  
• 
Blood Pressure and Heart Rate Increases: In a clinical study in adult participants (18 to 
60 years of age), 52/178 (29%) of participants treated daily with Qelbree (200 mg to 
600 mg) had a >20 beat per minute (bpm) increase in pulse rate at any time point in 
the clinical trial, compared to 23/181 (13%) of participants who received placebo. Of 
participants treated daily with Qelbree (200 to 600 mg), 23/178 (13%) had a ≥ 15 
mmHg increase in diastolic blood pressure at any time in the clinical trial, compared 
to 16/181 (9%) of participants in the placebo group. 
• 
Somnolence and Fatigue: In adults, somnolence was reported in 6% of Qelbree-
treated participants versus 2% in placebo-treated participants. Fatigue was reported 
in 12% of Qelbree-treated participants versus 3% of placebo-treated participants. 
• 
Activation of Mania or Hypomania: Noradrenergic drugs, such as Qelbree, may 
induce a manic or mixed episode in participants with bipolar disorder.  
The safety of Qelbree has also been evaluated in 159 adults (18 to 60 years of age) with 
ADHD [e.g., completed the adult Phase 3 trial (812P306)] who were exposed to one or more 
doses ranging from 200 mg to 600 mg QD in a long-term (up to 156 weeks; 3 years), open-
label extension safety trial (Study 812P311). All participants initiated Qelbree at 200 mg once 
daily (first 58 participants were instructed to titrate up to 400 mg after 1 week; for all 
subsequent participants, any dose adjustment following Visit 1 did not occur until end of 
Week 2 at Visit 2). All participants completed 3 visits during the first 12 weeks (Optimization 
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optimal dose. Following the Optimization Phase, participants completed regular study visits 
to assess safety/efficacy every 8 weeks for up to another 144 weeks (~3 years total); maximum 
exposure was 124 weeks. 
Adverse Events were reported in 115 (72.3%) participants. The most frequently reported AEs 
were insomnia, nausea, headache, fatigue, corona virus infection, anxiety, dry mouth, and 
vomiting. AEs for most participants were considered mild [n=42 (26.4%)] or moderate [n=64 
(40.3%)] in severity and related to study medication [n=82 (51.6%)] by the Investigator. AEs 
leading to permanent study medication discontinuation occurred in 28 (17.6%) participants. 
SAEs were reported in 2 (1.3%) participants (syncope/fall/spinal column injury; deep vein 
thrombosis/pulmonary embolism); neither were considered related to the study medication 
by the Investigator. No deaths occurred during the study. 
3.3.2 
Known Potential Benefits 
Qelbree is the first non-stimulant approved for adult ADHD in over 20 years. Qelbree has 
been proven to significantly reduce ADHD symptoms, including symptoms of inattention and 
hyperactivity/impulsivity as early as Week 2. Qelbree is dosed once-daily, can be taken with 
or without food, and its extended-release formula provides 24-hour exposure. Studies with 
Qelbree have shown no evidence of abuse potential and its once-daily dosing minimizes the 
risk of treatment abuse, misuse, or diversion. Furthermore, studies have not reported 
withdrawal symptoms or signs of dependence reported as AEs in clinical trials (Qelbree HCP, 
n.d.).  
3.3.3 
Assessment of Potential Risks and Benefits  
Viloxazine extended-release capsules (Qelbree) is a novel nonstimulant that is US FDA 
approved for the treatment of ADHD in patients 6 years of age and older based on positive 
results from three pediatric pivotal phase III trials and one adult phase III trial. In adults, 
treatment with viloxazine ER resulted in a statistically significant improvement on the AISRS, 
indicating an improvement in ADHD symptoms and associated functional impairment after 
only 2 weeks of treatment, and was demonstrable until the end of the study. Furthermore, 
safety data provided in adults with ADHD indicate viloxazine ER was tolerated with no 
reported serious AEs and <10% of viloxazine ER-treated participants discontinuing as a result 
of an AE. Viloxazine ER was generally regarded as safe with most reported TEAEs being 
assessed by Investigators as “mild” or “moderate” in severity.4 
This study aims to confirm the findings reported in controlled clinical trials in a real-world 
setting. Given the findings reported during Qelbree’s clinical development, participants of 
this study are expected to receive improvement in ADHD symptoms, executive functioning, 
and overall clinical improvement.  
Given the known risks of treatment with Qelbree, this study will closely monitor participants 
for AEs. This study will closely monitor participants using standardized and validated clinical-
rated scales for behavior change or worsening of behavior. Participants will be shipped a 
BP/PR cuff for monitoring potential increases in blood pressure and pulse rate. Participants 
will also be monitored for mania or hypomania while on treatment. Participants will be 
advised to exercise caution when driving or operating hazardous machinery due to the 
potential for somnolence and fatigue with treatment. 

           
 
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6. Study Design  
This is a Phase IV, open-label, fully decentralized clinical trial to evaluate the efficacy and 
safety of Qelbree in adults with ADHD and Mood Symptoms (Figure 1). Participants will 
complete patient-reported outcome (PRO) measures on the study mobile app, and 
participate in televisits with a qualified, trained rater or assessor (Table 1).  
Figure 1. Protocol Schema 
 
6.1 
Screening Period 
The duration of the screening period is up to 4 weeks (28 days) starting from the date of 
Screening televisit (e.g. Televisit #1a) after obtaining informed consent. The Screening Period 
includes two virtual televisits. The first televisit should occur within 3 weeks after the date of 
obtaining informed consent. If a potential participant is still considered eligible after Televisit 
1a, the second screening televisit will be scheduled; Televisit 1b should occur tentatively no 
later than a week prior to participant taking first dose of study medication. If participants 
prefer, Televisit #1a and #1b can be combined and completed in a single visit (Table 1). 
6.1.1 
Televisit #1a:  
After signing the eIC, the following will be administered/obtained/collected by a trained 
assessor at televisit, unless otherwise noted (Table 1): 
• 
Demographic information and Height  
• 
Medical/Psychiatric/Social History  
• 
Reproductive/Menstrual Cycle History Questionnaire; biological females only  
• 
MINI-AS   
• 
Prior Medications (past 12 months) and Concomitant Medications 
• 
C-SSRS ‘Baseline/Screening’ Version  
• 
Review Inclusion and Exclusion Criteria 

           
 
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6.1.2 
Televisit #1b:  
The following will be administered/obtained/collected by a qualified/trained rater or assessor 
during televisit (Table 1): 
• 
AISRS  
• 
CGI-S  
• 
SIGMA 
• 
SIGH-A 
• 
C-SSRS ‘Since Last Visit’ Version  
• 
Review Concomitant Medications 
• 
Review Inclusion and Exclusion Criteria  
If participant is still considered eligible: 
1. The participant will complete the following via the study mobile app: 
• 
Training Module 
• 
ASRSv1.1-SC 
• 
PHQ-8 
• 
GAD-7 
• 
WPAI:SHP  
• 
PSQI 
• 
BRIEF-A 
2. Schedule next televisits (Week 4, 9, and 14). 
3. The following items will be shipped to participant’s home address: 
• 
Blood pressure cuff to measure and report blood pressure and pulse rate 
• 
Urine Pregnancy Test (UPT) for females of childbearing potential (FOCP). A negative 
pregnancy test is required to continue participation in the study.  
• 
First shipment of study medication 
Once the shipment has been received, participants will report their first blood pressure and 
pulse rate reading and UPT result (FOCPs only) in the study mobile app. At all other 
timepoints in the study this information will be reported during the televisit (Table 1).  
6.2 
Treatment Period 
The first shipment will contain sufficient medication for the first 4 weeks of the study, after 
which, two more shipments will be triggered for ongoing treatment based on participant 
response and PI or designee’s prescription. 
Once study medication is received, the participant will confirm receipt and administration of 
the first dose within the study mobile app. At all other timepoints, dosing information will be 
captured during the televisit.  
A televisit will be scheduled 4 weeks (28 days), 9 weeks (63 days ) and 14 weeks (98 days) 
after date of first dose (Table 1, Figure 1). Participants will need to continue to take study 
medication as per the instructions provided by the Investigator during the Treatment Period. 

           
 
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During the Televisit #2 and #3 (Weeks 4 and 9), the following will be administered, obtained 
or collected by a qualified/trained rater or assessor (ClinRO efficacy assessments should not 
be administered if participant is discontinuing and has not taken daily dose of Qelbree for >7 
consecutive days prior to the televisit): 
• 
AISRS  
• 
CGI-S  
• 
CGI-C 
• 
C-SSRS ‘Since Last Visit’ Version  
• 
Review AEs 
• 
Review Concomitant Medications 
• 
Report systolic/diastolic blood pressure, pulse rate, and weight  
• 
Report UPT results (FOCPs only) 
• 
RMCH Questionnaire’s Menstrual-Question #5 (FOCPs only) 
• 
SM accountability; Report the number of remaining capsules in bottle  
• 
Confirm or reschedule next virtual visit (Week 9 and Week 14, as applicable) 
In addition, at Weeks 4 and 9, the participant will complete the following via the study mobile 
app (PRO efficacy assessments should not be administered if participant is discontinuing and 
has not taken daily dose of Qelbree for >7 consecutive days prior to attempting them): 
• 
SM administration mode/time query; report admin method and average admin time  
• 
ASRSv1.1-SC 
• 
PHQ-8 
• 
GAD-7 
• 
WPAI:SHP 
During the treatment period, participants should continue all current medications or other 
treatment regimens as prescribed by their primary care physician. Their primary care 
physician will determine changes to these regimens according to routine clinical practice, but 
participants should be reminded to report changes in concomitant medications (e.g., new 
medication started, current medication discontinued, or dose reduced, etc.) to the study staff 
between televisits. Participants may withdraw consent or PI/designee can discontinue a 
participant if they feel it is no longer in the best interest of the participant to continue in the 
study. If the participant’s participation ends prior to Week 14 of treatment, the reason for 
discontinuation will be captured by the study staff. 
6.3 
End of Study  
During the Televisit #4 (Week 14/EOS), the following will be administered, obtained or 
collected by a qualified/trained rater (Table 1; ClinRO efficacy assessments should not be 
administered if participant has not taken daily dose of Qelbree for >7 consecutive days 
prior): 
• 
AISRS  
• 
CGI-S  
• 
CGI-C 
• 
SIGMA 

           
 
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• 
SIGH-A 
• 
C-SSRS ‘Since Last Visit’ Version  
• 
Review AEs 
• 
Review Concomitant Medications 
• 
Report systolic/diastolic blood pressure, pulse rate, and weight  
• 
Report UPT results (FOCPs only) 
• 
RMCH Questionnaire’s Menstrual-Question #5 (FOCPs only) 
• 
SM accountability; report the number of remaining capsules in bottle  
• 
Schedule safety follow-up televisit 
In addition, at Week 14/EOS, the participant will complete or report the following via the 
study mobile app (efficacy assessments should not be administered if participant has not 
taken daily dose of Qelbree for >7 consecutive days prior): 
• 
SM administration mode/time query; report admin method and average admin time  
• 
ASRSv1.1-SC 
• 
PHQ-8 
• 
GAD-7 
• 
WPAI:SHP 
• 
PSQI 
• 
BRIEF-A 
If participant discontinues early (Early-Termination), perform Week 14 assessments; however, 
ClinRO/PRO efficacy assessments should not be administered if participant has not taken 
daily dose of Qelbree for >7 consecutive days prior. 
6.4 
Safety Follow-up (SF) Televisit 
A week following participant’s last dose of study medication, a safety follow-up televisit will 
be conducted to review AEs and Concomitant Medications (Table 1).  

           
 
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7. Study Population 
7.1 
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 to provide and sign electronic informed consent.  
3. Has a primary diagnosis of ADHD based on the Diagnostic and Statistical Manual of 
Mental Disorders; Fifth Edition, Text Revised (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: 
a. Has undergone menopause, defined as a biological female who reports 
amenorrhea for at least 12 consecutive months prior to providing informed 
consent.  
b. 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. 
c. Has had bilateral tubal ligation, hysterectomy, bilateral oophorectomy 
(permanently sterilized) at least 6 months prior to providing informed.  
8. If potential participant is a biological male, one of the following must be met: 
a. 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. 
b. 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, 

           
 
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and is willing to have visual telemedicine appointments (televisits) at times designated 
in the study protocol. 
7.2 
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 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: 
a) A current diagnosis of a major neurological disorder; or 
b) Seizures, seizure disorder or seizure-like events; or a history of seizure disorder 
within the immediate family (siblings, parents); or 
c) 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. 

           
 
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12. In the Investigator’s opinion, is unlikely to comply with the protocol or is unsuitable for 
any other reason. 
7.3 
Screen Failures 
Participants who are consented to participate in the clinical trial, who do not meet one or 
more criteria required for participation in the trial during the screening procedures, are 
considered screen failures.  
On a case-by-case basis, participants who previously screened for this study (e.g., provided 
informed consent), but were not dispensed SM may be allowed to rescreen for this study, but 
only after receiving written permission from sponsor and medical monitor.  
7.4 
Recruitment and Retention 
Participants will be targeted for recruitment using digital and social media advertisements, 
and referrals from physicians' existing patient pool, within the contiguous US. A sufficient 
number of individuals will be screened to obtain up to 750 participants who will be dosed. 
An anticipated attrition rate of 33% is expected to result in the completion of up to 500 
participants through the treatment period (14 weeks). Participants will have completed the 
study upon completion of all study procedures, assessments, and observations through the 
end of Week 14 of treatment. 
8. Study Treatment 
8.1 
Study Treatment Description 
Qelbree (viloxazine extended-release capsules) is a selective norepinephrine reuptake 
inhibitor indicated for the treatment of ADHD in adults and pediatric patients 6 years and 
older. Qelbree received marketing approval in the US in 2021 for pediatric patients 6-17 
years of age, and in 2022 for adults ≥18 years of age (Qelbree PI). 
8.2 
Study Treatment Administration 
8.2.1 
Study Medication  
Qelbree (viloxazine extended-release capsules) is supplied in 100 mg, 150 mg, and 200 mg 
capsules (Qelbree PI).  
8.2.2 
Dosing 
Participants will be instructed to take Qelbree 200 mg once daily (QD) in the morning during 
Week 1 and 400 mg QD in the morning during Week 2 onwards until next contact with 
Investigator. The investigator may adjust/titrate dosage in increments of up to 200 mg weekly 
to the maximum recommended dosage of 600 mg once daily, depending on response and 
tolerability. At the discretion of the Investigator based on tolerability, the participant may be 

           
 
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instructed to take total daily dose once daily in the evening. See full prescribing information 
for Qelbree regarding participants who have severe renal impairment. 
8.2.3 
Mode of Administration 
Qelbree is administered orally, with or without food. Qelbree capsules should not be cut, 
crushed, or chewed. Qelbree capsules should be swallowed whole, and if swallowing the 
capsule(s) whole is difficult, the capsule(s) can be opened, and the entire contents can be 
sprinkled over a teaspoonful or tablespoonful of pudding or applesauce. This mixture must 
be consumed entirely, without chewing, within 15 minutes for pudding or within 2 hours for 
applesauce. This mixture must not be stored for future use. 
At Week 4, 9 and 14, participant will report the method of oral administration that was used 
during the past 4-5 weeks of treatment, e.g., in the past 4 or 5 weeks: (a) I swallowed intact 
capsule whole each time; (b) I swallowed food mixture each time; or (c) I used both methods 
to swallow study medication. In addition, at Week 4, 9 and 14, the participant will report the 
average clock time (hh:mm AM/PM) or time of day range that he/she took their daily dose of 
study medication during past 4-5 weeks. 
For warnings and precautions, refer to full prescribing information for Qelbree. 
8.3 
Study Product Preparation/Handling/Storage/Accountability 
Qelbree (viloxazine extended-release capsules) are available in the following strengths and 
colors: 
• 
100mg (yellow capsule printed with “SPN” on capsule cap and “100” on capsule body 
with edible black ink). 
• 
150mg (lavender capsule printed with “SPN” on capsule cap and “150” on capsule 
body with edible black ink). 
• 
200mg (light green capsule printed with “SPN” on capsule cap and “200” on capsule 
body with edible black ink). 
Storage and Handling 
• 
Qelbree should be stored at 20°C to 25°C (68°F to 77°F); excursions are permitted 
between 15°C to 30°C (59°F to 86°F). 
8.4 
Concomitant Diets, Treatments, and Medications 
8.4.1 
Contraindications 
Qelbree is contraindicated in participants: 
• 
receiving concomitant treatment with monoamine oxidase inhibitors (MAOI), or within 
14 days following discontinuing an MAOI, because of an increased risk of 
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• 
receiving concomitant administration of sensitive CYP1A2 substrates or CYP1A2 
substrates with a narrow therapeutic range. 
For drug interactions, refer to full prescribing information for Qelbree. 
Furthermore, participants that are currently undergoing treatment for substance use disorder 
(if participant is stable/in recovery; with or without medication-assisted treatment), may be 
allowed to participate in this study on a case-by-case basis with Sponsor input. 
 
All concomitant medications will be recorded in the eCRF. If a participant is taking a stimulant 
medication that is commercially available in a short-acting (immediate-release) and a long-
acting (extended-release, prolonged release, etc.) formulation, also record in parentheses 
next to the name of stimulant in ConMeds page in participant’s eCRF whether the 
participant’s stimulant medication is either a short-acting [e.g., methylphenidate (IR), 
amphetamine [IR], etc.] or a long-acting [i.e., methylphenidate (ER), amphetamine [XR], etc.) 
formulation.  
9. Study Assessments and Procedures 
9.1 
Screening Assessments 
9.1.1 
Psychiatric Diagnostic Instruments 
9.1.1.1 
Mini-International Neuropsychiatric Interview for ADHD Studies (MINI-AS) 
The Mini International Neuropsychiatric Interview (MINI) was developed and designed as a 
brief structured diagnostic interview for the major psychiatric disorders in DSM-III-R, DSM-IV 
and DSM-5 and ICD-10 (Sheehan et al., 1997; Lecrubier et al., 1997; Sheehan et al., 1998). 
Validation and reliability studies have shown that the MINI has similar reliability and validity 
properties to similar instruments, however administration duration of time of the MINI is 
much shorter than the other diagnostic instruments. The standard MINI assesses the 17 most 
common mental health disorders (e.g., current prevalence rates of 0.5% or higher in the 
general population in epidemiology studies) using branching tree logic. Compared to the 
standard MINI, the MINI-AS version has a more detailed set of questions for each of the nine 
Psychotic Disorders. It is suitable for clinical and research settings where Psychotic Disorders 
are a focus of interest and where it is important to differentiate between the different 
psychotic disorders (e.g., schizophrenia vs schizoaffective disorder). The standard MINI does 
assess both Major Depressive Disorder with Psychotic Features and Bipolar I Disorder with 
Psychotic Features. Otherwise, all the other modules are similar to the standard MINI.  
As outlined in Section 6.1.1, a diagnosis of ADHD is confirmed via MINI-AS by trained central 
assessor/psychiatrist.  

           
 
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9.2 
Efficacy Assessments 
9.2.1 
Clinician-Rated Outcomes (ClinROs) 
As outlined in Section 6.1.2, once a diagnosis of ADHD is confirmed, all clinician-rated 
outcome assessments will be administered by trained central raters or psychiatric nurse 
practitioners for reliability of data captured. ClinRO efficacy assessments should not be 
administered if participant is discontinuing and has not taken daily dose of Qelbree for >7 
consecutive days prior to televisit.  
9.2.1.1 
Adult ADHD Investigator Symptom Rating Scale (AISRS) 
The adult ADHD Investigator Symptom Rating Scale (AISRS) was developed to better 
measure the presence and severity of ADHD symptoms based on DSM-IV diagnostic criteria 
in adult participants (Spencer et al., 2010). It is a semi-structured clinical interview with 
suggested prompts for each item to improve interrater reliability. The scale consists of 18 
items that directly correspond to the 18 symptoms of ADHD and are further subdivided into 
two subscales: Inattention (9 items) and Hyperactivity/Impulsivity (9 items). During the 
interview with the participant, the clinician/Investigator rates the frequency and severity of 
each symptom on a 4-point Likert-type scale, where 0 = None, 1 = Mild, 2 = Moderate, and 3 
= Severe, with a maximum total score of 54 points and maximum subscale score of 27 points. 
The scale allows the assessment of functional impairments linked to each symptom 
dimension. The AISRS Total score is the sum of all 18 items (or sum of the Inattention and 
Hyperactivity/Impulsivity subscale scores). The AISRS is being used in this study to assess 
efficacy of Qelbree in the treatment of ADHD in adults with mood disorders. The AISRS Totals 
and Subscale scores are the primary outcome measures for this study. 
9.2.1.2 
Clinical Global Impressions of Severity/Change (CGI-S/C) Scales 
The Clinical Global Impression scale was developed to provide a brief, stand-alone 
assessment of the clinician’s view of a participant’s global functioning prior to and after 
administration of SM (Guy, 1976). The Clinical Global Impression of Severity (CGI-S) scale is a 
single item clinician rating of clinician’s assessment of the severity of the ADHD symptoms in 
relation to the clinician’s total experience with patients with ADHD. The CGI-S is evaluated on 
a 7-point scale with 1 = Asymptomatic, no symptoms, 2 = Borderline, 3 = Mild, 4 = Moderate, 
5 = Marked, 6 = Severe, and 7 = Among the most extreme. Successful therapy is indicated by 
a lower overall score in subsequent testing. The Clinical Global Impression of Change (CGI-C) 
scale is a single item clinician assessment of how much the patient’s ADHD symptoms have 
changed (improved, worsened or no change) during treatment relative to his/her baseline 
state prior to the beginning of treatment. The CGI-C is evaluated on a 7-point scale with 1 = 
Very much improved, 2 = Much improved, 3 = Minimally improved, 4 = No change, 5 = 
Minimally worse, 6 = Much worse, and 7 = Very much worse. Successful therapy is indicated 
by a score <4 in subsequent testing. The CGI is being used in this study to assess efficacy of 
Qelbree in the treatment of ADHD in adults with mood disorders. The CGI-S/C scores are 
secondary outcome measures for this study. 

           
 
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9.2.1.3 
Montgomery–Åsberg Depression Rating Scale (MADRS) 
The Montgomery–Åsberg Depression Rating Scale (MADRS) is a 10-item investigator-rated 
diagnostic questionnaire used to measure the severity of depressive episodes in participants 
with mood disorders and is designed to be sensitive to changes brought on by treatment 
(Montgomery and Åsberg, 1979). A structured interview guide for the Montgomery–Åsberg 
Depression Rating Scale (SIGMA) was developed to improve consistency on how the scale is 
administered among clinicians/raters across study sites or clinical trials and to improve the 
reliability of the ratings (Williams and Kobak, 2008). The questionnaire assesses the severity 
of the following 10 symptoms: (1) Apparent sadness; (2) Reported sadness; (3) Inner tension; 
(4) Reduced sleep; (5) Reduced appetite; (6) Concentration difficulties; (7) Lassitude; (8) 
Inability to feel; (9) Pessimistic thoughts; (10) Suicidal thoughts. Nine of the items are based 
upon patient report, and one is on the rater’s observation during the rating interview. Each 
MADRS item/symptoms is rated on a 7-point Likert scale (0–6 continuum, where 0=no 
abnormality to 6=severe); point can be defined rating (0, 2, 4, 6) or points between them (1, 
3, 5). The overall score ranges from 0 to 60. A higher MADRS total score indicates more 
severe depression; total score ranges of 0 to 6 indicate normal/symptom absent, 7 to 19 
indicate mild depression, 20 to 34 indicate moderate depression, >34 indicate severe 
depression (Snaith et al., 1986; Herrmann et al., 1998; Müller et al., 2000). It takes about 25-
45 minutes to complete the SIGMA. The MADRS is being used in this study to assess 
symptoms of depression during Qelbree treatment in adults with ADHD. The MADRS Total 
score is a secondary outcome measure for this study. 
9.2.1.4 
Hamilton Anxiety Rating Scale (HAM-A) 
The Hamilton Anxiety Rating Scale (HAM-A) is a rating scale developed to assess/measure the 
severity of an individual’s anxiety (Hamilton, 1959). The HAM-A is used to assess severity of 
anxiety in children, adolescents and adults in both clinical and research settings (Hamilton, 
1959; Maier et al., 1988; Borkovec and Costello, 1993). The HAM-A consists of 14 items or 
parameters, each defined by a series of symptoms. It measures both psychic anxiety (mental 
agitation and psychological distress) and somatic anxiety (physical complaints related to 
anxiety). The original HAM-A does not provide any standardized probe questions. Therefore, 
a structured interview guide for the Hamilton Anxiety Rating Scale (SIGH-A) was developed to 
instructions for administration and clear anchor points for the assignment of severity ratings 
(Shear et al., 2001). Each item on the HAM-A is rated/scored on a 5-point Likert scale, where 
0 = Not present, 1 = Mild, 2 = Moderate, 3 = Severe, and 4 = Very severe. The ratings/scores 
of all 14 items are summated to yield a total score (ranging from 0 to 56), where ≤ 17 
indicates “mild anxiety severity,” 18 to 24 indicates “moderate anxiety severity,” 25 to 30 
indicates “moderate to severe anxiety severity,” and ≥ 31 indicates “severe anxiety.” It takes 
25 to 35 minutes to complete the HAM-A. The HAM-A is being used in this study to assess 
symptoms of anxiety during Qelbree treatment in adults with ADHD. The HAM-A Total score 
is a secondary outcome measure for this study. 

           
 
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9.2.2 
Patient-Reported Outcomes (PROs) 
As outlined in Section 6.1.2, once a diagnosis of ADHD is confirmed and ClinROs have been 
completed, eligible participants will complete patient-reported outcome assessments via the 
study mobile app prior to first dose (e.g., during virtual visit #2, if necessary). During the 
Treatment Period, following first dose, the PRO efficacy assessments should not be 
administered if participant is discontinuing and has not taken daily dose of Qelbree for >7 
consecutive days prior.  
9.2.2.1 
Adult ADHD Self-Report Scale v1.1 Symptom Checklist (ASRSv1.1-SC) 
The Adult ADHD Self-Report Scale v1.1 Symptom Checklist (ASRSv1.1-SC) was developed in 
conjunction with the World Health Organization (WHO) and the Workgroup on Adult ADHD 
to help screen for ADHD in adult participants based on DSM-IV diagnostic criteria (Kessler et 
al., 2005; Adler et al., 2006; Adler et al., 2019). The ASRSv1.1-SC consists of 18 items that 
correspond to the 18 DSM-IV symptoms of ADHD, which are further subdivided into two 
subscales: Inattention (IA; 9 items: 1 to 4 and 7 to 11) and Hyperactivity/Impulsivity (HI; 9 
items; 5, 6, and 12 to 18) to allow assessment of functional impairments linked to each 
symptom dimension. Individuals rate the frequency of each symptom on a 5-point scale 
(where 0 = Never, 1 = Rarely, 2 = Sometimes, 3 = Often, and 4 = Very Often) based on their 
experience over an indicated period of time (e.g., in the past week). The ASRSv1.1-SC ratings 
can be evaluated as a categorical (Screener and ADHD Presentation Type) or continuous 
variable (Total and Subscale scores) as follows: 
• As a categorical variable, absolute ratings (0-4) are first converted to a binary score (1 or 
0). For instance, for items 1 to 3, 9, 12, 16, and 18 ratings of Sometimes, Often, and Very 
Often are assigned a value of 1 and ratings of Never and Rarely are assigned a value of 0. 
For the remaining 11 items (4 to 8, 10 and 11, 13 to 15, and 17) ratings of Often and Very 
Often are assigned a value of 1 and ratings of Never, Rarely, and Sometimes are assigned 
a value of 0. For the Screener, if the sum of the binary scores for six items (items 1 to 6) is 
≥4 then the patient is considered to have symptoms highly consistent with ADHD in 
adults. For ADHD Presentation Type, if sum of the binary score of the 9 IA items or the 9 
HI items is ≥ 6 then the patient is considered to be symptomatic for AI and/or HI, 
respectively.  
• As a continuous variable, the sum of absolute rating (0-4) of all18 items yields the 
absolute Total score (range 0 to 72: the higher the score, the more severe the ADHD 
symptoms). The sum of the absolute rating of the 9 IA items or the 9 HI items yields 
absolute Subscale score (range 0 to 36: the higher the score, the more severe the IA or 
HI symptoms, respectively).  
It takes approximately 5 minutes to complete the ASRSv1.1-SC. The ASRSv1.1-SC is being 
used in this study to characterize ADHD symptoms at baseline (categorical) prior to treatment 
and to assess efficacy (continuous variable)of Qelbree in the treatment of ADHD in adults. 
The absolute ASRSv1.1-SC Totals and Subscale scores are secondary outcome measures for 
this study. 

           
 
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9.2.2.2 
Patient Health Questionnaire (PHQ-8) 
The Patient Health Questionnaire (PHQ) is a multipurpose instrument for screening, 
diagnosing, monitoring and measuring the severity of depression (Spitzer et al., 1999; Spitzer 
et al., 2000; Kroenke et al., 2001). The initial 9-item version (PHQ-9) incorporates DSM-IV 
depression diagnostic criteria with other leading major depressive symptoms into a brief self-
report tool. It is one of the most validated tools in mental health which can assist clinicians 
with diagnosing depression and assist researchers with monitoring treatment response. 
Research has shown that certain scores on the PHQ-9 are strongly correlated with a 
subsequent major depression diagnosis. However, not everyone with an elevated PHQ-9 is 
certain to have major depression. The PHQ-9 is a self-administered version of the PRIME-MD 
diagnostic instrument for common mental disorders (Kroenke et al., 2001). Since the C-SSRS 
is being administered at screening and follow up during treatment in this study, the PHQ-8 
will be administered in this study (e.g., 8-item depression scale with item #9 for suicide risk 
omitted). The PHQ-8 has been validated as a diagnostic and severity measure for depressive 
disorders in large clinical studies (Kroenke et al., 2009). The PHQ-8 is the depression module, 
which the patient scores each on 4-point Likert scale, including 0 = not at all; 1 = several days, 
2 = more than half the days, and 3 = nearly every day; sum of all items yields total score (0-
24). PHQ-8 total scores ≥10 indicate major depression and ≥20 indicate severe major 
depression. The PHQ-8 takes less than 5 minutes to complete. The PHQ is being used in this 
study to assess self-reported symptoms of depression during Qelbree treatment in adults 
with ADHD. The PHQ-8 Total score is a secondary outcome measure for this study. 
9.2.2.3 
General Anxiety Disorder-7 item (GAD-7) Scale 
Generalized Anxiety Disorder 7 scale (GAD-7) is a self-reported 7-item questionnaire for 
screening and measuring the severity of generalized anxiety disorder (Spitzer et al., 2006). 
The GAD-7 measures the severity of various symptoms of generalized anxiety disorder over 
the past 2 weeks according to reported response categories with assigned points. The 
patient scores each GAD-7 item on 4-point Likert scale, where 0 = Not at all, 1 = Several days, 
2 = Over half the days, and 3 = Nearly every day. The clinician/Investigator can obtain the 
total score by summating all 7 items. GAD 7 total scores range from 0 to 21, where a total 
score of 1 to 4 = None/Minimal anxiety, 5 to 9 = Mild anxiety, 10 to 14 = Moderate anxiety, 
and ≥ 15 = Severe anxiety. It takes less than 5 minutes to complete the GAD-7. The GAD-7 is 
being used in this study to assess self-reported symptoms anxiety during Qelbree treatment 
in adults with ADHD. The GAD-7 Total score is a secondary outcome measure for this study. 
9.2.2.4 
Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A) 
The Behavior Rating Inventory of Executive Function–Adult Version (BRIEF-A; Self report) is a 
standardized rating scale that captures views of an individual’s executive functions into 
everyday behaviors in adults ages 18 to 90 years (Roth et al., 2005; Roth et al., 2013). It has 
been utilized in clinical trials to assess changes in executive function with treatment for 
neurological and psychiatric disorders, including ADHD (Adler et al., 2014). The self-report 

           
 
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provides the insight of the individual’s viewpoint of their own difficulties in self-regulation. 
The BRIEF-A is a 75-item self-rating scale that assesses overall functioning (Global Executive 
Function [GEC]) and 9 non-overlapping scales among 2 summary index scales. 
(Metacognition Index [MI] and Behavioral Regulation Index [BRI]) that assess aspects of 
executive function and problems with self-regulation from the perspective of the individual. 
Description of the nine BRIEF-A scales (Roth et al., 2013) by summary index scale: 
1. The Behavioral Regulation Index (BRI) captures the ability to maintain appropriate 
regulatory control of one’s own behavior and emotional responses. The BRI is broken 
down into the following four scales within the BRIEF-A: 
• Inhibit: Control impulses; appropriately stop verbal, attentional, physical behavior at 
the proper time 
• Shift: Move freely from one situation, activity, or aspect of a problem to another as the 
situation demands; think flexibly to aid problem-solving 
• Emotional control: Modulate one’s emotional responses appropriately 
• Self-Monitor: Recognize the effect of one’s own behavior on others  
2. The Metacognition Index (MI) reflects the individual’s ability to initiate activity and 
generate problem-solving ideas, to sustain working memory, to plan and organize 
problem-solving approaches, to monitor success and failure in problem solving, and to 
organize one’s materials and environment. The MI is broken down into the following four 
scales within the BRIEF-A: 
• Initiate: Begin a task or activity without external prompting; independently generate 
ideas 
• Working memory: Hold information in mind in order to complete a task; stay with, or 
stick to, an activity 
• Plan/organize: Anticipate future events; set goals; develop steps ahead of time to 
carry out a task; organize information and behavior to achieve and objective; carry out 
tasks in a systematic manner 
• Task Monitor: Assess performance during or after finishing a task for mistakes 
• Organization of Materials: Keep workspace and living areas in an orderly manner; 
keep track of materials needed for tasks 
Participants rate each item on a 3-point scale (1=Never, 2=Sometimes, or 3=Often) based on 
their experience within the last month. The sum of 70 items yields the GEC raw score (range: 
70-210), the sum of 40 items yields the MI raw score (range: 40-120), the sum of 30 items 
yields the BRI raw score (range: 30-90), the sum of 8 items yields the “Inhibit” raw score 
(range: 8-24), the sum of 6 items yields the ”Shift” raw score (range: 6-18), the sum of 10 
items yields the “Emotional Control” raw score (range: 10-30), sum of 6 items yields the “Self-
Monitor” raw score (range: 6-18), sum of 8 items yields the “Initiate” scale raw score (range: 8-
24), the sum of 10 items yields the “Plan/Organize” raw score (range: 10-30), the sum of 6 
items yields the “Task Monitor” raw score (range: 6-18), the sum of 8 items yields the 

           
 
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”Organization of Material” raw score (range: 8-24), and the sum of 8 items yields the 
“Working Memory” raw score (range: 8-24). Raw scores are converted to a T-score (normative 
population mean=50 and standard deviation=10; T-score ≥ 65 is considered abnormally 
elevated). It takes 15-20 minutes to complete the BRIEF-A. The BRIEF-A is being used in this 
study to assess self-reported executive function during Qelbree treatment in adults with 
ADHD. The BRIEF-A T-scores for GEC, BRI, MI and the nine individual scales are secondary 
outcome measures for this study. 
9.2.2.5 
Work Productivity and Activity Impairment: Specific Health Problem 
(WPAI:SHP) 
The Work Productivity and Activity Impairment (WPAI) Questionnaire is a self-assessment 
questionnaire that measures the impact of health problems on work productivity and regular 
activities (Reilly et al., 1993). There are WPAI versions that assesses based on a general health 
problem (WPAI:GH) or based on specific health problem (WPAI:SHP; e.g., ADHD). The 
WPAI:SHP will be used in this study. The WPAI questionnaire has been used to clinical 
research to assess the impact of ADHD and ADHD treatments on work productivity and 
regular activities in adults with ADHD (Pawaskar et al., 2020; Spaulding et al., 2022; Schein et 
al., 2023; Lee et al., 2023). The WPAI:SHP questionnaire consists of six questions that ask 
about employment status (Q1), the number of hours missed from work or regular activities 
due to the specific health problem or other reasons (Q2, Q3), the number of hours actually 
worked (Q4), and the degree of impairment while working or performing regular activities 
(Q5, Q6) on an 11-point scale (where 0 = “PROBLEM (My ADHD symptoms) had no effect on 
my work/ daily activities” and 10 = “PROBLEM (My ADHD symptoms) completely prevented 
me from doing my work/ daily activities . The WPAI:SHP questionnaire can be used to 
calculate four outputs: Absenteeism percentage , Presenteeism percentage, Work 
Productivity Loss percentage, and Activity Impairment percentage.  It takes 2-3 minutes to 
complete the WPAI:SHP. The WPAI:SHP scores/percents are secondary outcome measures 
for this study. 
9.2.2.6 
Pittsburgh Sleep Quality Index (PSQI) 
The Pittsburgh Sleep Quality Index (PSQI) is a validated and effective instrument used to 
measure the quality and patterns of sleep in adults (Buysse et al., 1989). The PSQI is a self-
rated questionnaire which assesses sleep quality and disturbances over a 1-month time 
interval. It is a 19-item questionnaire out of which generate 7 component scores (or domains): 
subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep 
disturbances, use of sleep medication, and daytime dysfunction over the last month. The 
individual rates each of these seven areas of sleep. Scoring of the answers is based on a 0 to 
3 scale, whereby 3 reflects the negative extreme on the Likert Scale. A global sum of “5” or 
greater indicates a “poor” sleeper. Although there are several questions that request the 
evaluation of the client’s bedmate or roommate, these are not scored, nor reflected in the 
attached instrument. An updated scoring was established from original scoring algorithm: if 

           
 
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5J is not complete or the value is missing, it now counts as a “0”. It takes 10-15 minutes to 
complete the PSQI. The PSQI is being used in this study to assess self-reported sleep 
behavior and daytime function during Qelbree treatment in adults with ADHD. The PSQI 
global 
scores are secondary outcome measures for this study. 
9.3 
Questionnaires  
9.3.1 
Reproductive/Menstrual Cycle History (RMCH) Questionnaire 
All biologically female participants will be asked about timing of menarche, history of 
pregnancies, and current reproductive status at Screening. Those biologically female 
participants who are of childbearing potential will also be asked questions about their 
menstrual cycle in the past year at Screening. Those biologically female participants who are 
not of childbearing potential will be asked questions about when their menses stopped and 
the reason at Screening. At each Televisit FOCPs will report the date of their last menses 
(RMCH Questionnaire’s Menstrual-Question #5).  
9.4 
Safety Assessments 
The safety endpoints measured during this study are AEs, blood pressure/pulse rate, weight, 
and the Columbia Suicide Severity Rating Scale (C-SSRS). 
9.4.1 
Adverse Events 
Adverse events will be captured and/or recorded from the time the participant administers 
the first dose of study medication and until 30 days after last dose of study medication has 
been administered. Adverse events will be assessed/captured by assessor at every 
contact/televisit with participant. 
9.4.2 
Blood Pressure/Pulse Rate and Weight 
Blood pressure/pulse rate (BP/PR) and weight will be measured using BP/PR cuffs and weight 
scale, respectively. BP/PR cuffs will be shipped to participants. All participants will use the 
same BP/PR device for measurement consistency . Although the BP/PR device records each 
measurement/reading, systolic/diastolic BP and PR values will be captured by participant in 
study app at Screening and by assessor in eCRF during all other televisits during the 14-week 
treatment period. 
9.4.3 
Columbia-Suicide Severity Rating Scale (C-SSRS)  
Assessment of suicidal ideation and behavior will be conducted using the Columbia-Suicide 
Severity Rating Scale (C-SSRS) (Posner et al., 2011). The C-SSRS is an FDA-recommended 
prospective assessment instrument that directly classifies suicidal ideation and behavior 
events into 11 preferred categories, including 5 levels of suicidal ideation, 5 levels of suicidal 
behavior, and the category of self-injurious behaviors with no suicidal intent.  

           
 
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The instrument has been validated used successfully in adult participants with various 
psychiatric disorders that do not involve cognitive impairment. The C-SSRS outcomes that 
can be used for clinical management and safety monitoring are suicidal lethality rating, 
suicidal ideation score, and suicidal ideation intensity rating. The C-SSRS is a short 
questionnaire that can be administered quickly and consists of simple questions to assess the 
severity and immediacy of suicide risk. The C-SSRS will be administered by trained assessor 
during televisits during screening (Baseline/Screening version) and treatment (Since Last Visit 
version) periods. 
9.5 
Adverse Events 
9.5.1 
Definition of Adverse Events 
An AE means any untoward medical occurrence associated with the use of an intervention in 
humans, whether or not considered intervention-related (21 CFR 312.32 (a)). 
The use of the term “AE” does not imply a relationship with the study product or with the 
clinical study. AEs will be defined as falling into the categories “non-serious AE” and “SAE”.  
The AE may be a new illness, worsening of a concomitant illness, an effect of the study 
product, or a combination of two or more of these factors. 
9.5.2 
Definition of Serious Adverse Events 
An AE or suspected adverse reaction is considered "serious” if, in the view of either the 
Investigator or Sponsor, it results in any of the following outcomes: death, a life-threatening 
AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or 
significant incapacity or substantial disruption of the ability to conduct normal life functions, 
or a congenital anomaly/birth defect. Important medical events that may not result in death, 
be life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the participant and may require medical 
or surgical intervention to prevent one of the outcomes listed in this definition (21 CFR 
312.32 (a)). 
9.5.3 
Adverse Event Reporting 
For the purposes of this study, the period of observation for collection of AEs begins after the 
first dose is administered and continues through the completion of the study at Week 14 (end 
of treatment). Any health changes prior to first dose will be recorded as medical history.  
All AEs occurring during the study will be individually assessed by the Investigator, reported, 
and recorded, regardless of seriousness or relationship to the study product.  
The following information will be documented in each case: 
• 
Participant ID  
• 
AE Term 

           
 
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• 
Start Date of event 
• 
End Date of event or Ongoing 
• 
Severity or Intensity 
• 
Seriousness 
• 
Action taken with study product 
• 
Action taken to treat event 
• 
Outcome  
• 
Relationship to study product 
• 
Participant’s health status 
9.5.4 
Serious Adverse Event Reporting 
Documentation of an SAE requires that in addition to AE information provided in Section 9.5.3, 
the Investigator or designee will provide: 
• 
Seriousness criteria: life threatening, hospitalization, persistent/significant disability, 
congenital anomaly/birth defect, death [if marked, then date of death] 
• 
Event Description: where a narrative would capture the details of the event 
• 
Relevant Medical History: any medical history pertinent to the event 
• 
Other situations: 
o Medical or scientific judgment will be exercised by the Investigator in deciding 
whether SAE reporting is appropriate in other situations, such as significant 
medical events that may jeopardize the participant, and/or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive 
treatment for allergic bronchospasm, blood dyscrasias, convulsions or 
development of intervention dependency or intervention abuse. 
In addition, the Sponsor (via the Investigator or designee) will be notified of SAE via email 
within 24 hours of identifying it ( e.g. recorded in the SAE form). SAE meeting the Institutional 
Review Board (IRB) criteria for reporting will be reported to the IRB within the required 
timeline. SAEs which result in death or are life-threatening must be reported to IRB and 
Sponsor immediately.  
9.5.5 
Adverse Event Severity and Causality Assessments 
Assessment of Severity  
The severity of AEs will be defined by the following criteria.  
• 
Mild: Symptoms hardly perceived, only slight impairment of general well-being 
• 
Moderate: Clearly noticeable symptoms, but tolerable without immediate relief 
• 
Severe: Overwhelming discomfort 
Assessment of Causality  

           
 
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The Investigator or designee will assess the possibility of a link between the study product 
and an AE on the basis of the following criteria: 
• 
Unrelated 
  
o There is an evident other explanation for the AE 
o The AE is in accordance with the effect or adverse effect of the concomitant 
medication being taken by participant  
o The AE occurred prior to the administration of the study product 
• 
Unlikely relation 
o Reasonable temporal relationship with the intake of the study product, although 
there is another plausible explanation for the occurrence of the AE 
• 
Possible relation 
o Reasonable temporal relationship with the intake of the study product, although 
there are a number of other factors that could have caused the AE 
• 
Probable relation  
o Reasonable temporal relationship with the intake of the study product although 
other plausible reasons point to a causal relationship with the study product 
• 
Definite relation  
o Reasonable temporal relationship with the intake of the study product, and 
o There is no other explanation for the AE, and 
o Subsidence or disappearance of the AE on withdrawal of the study product 
(discontinuation), and 
o Recurrence of the symptoms on reintroduction of the study product 
Expected Adverse Events  
Expected AEs are known AEs based on previous findings from use of the products or 
procedures used in this study. The most commonly observed adverse reactions in adults are 
insomnia, headache, somnolence, fatigue, nausea, decreased appetite, dry mouth and 
constipation (Qelbree PI). 
Adverse events of concern include (1) suicidal thoughts and behavior, (2) blood pressure and 
pulse rate increases, (3) activation of mania or hypomania, and (4) somnolence and fatigue 
(Qelbree PI). 
Unanticipated Problems 
Definition  
Unanticipated problems (UAP) involving risks to particpants or others includes, in general, 
any incident, experience, or outcome that meets all of the following criteria:  
• 
Unexpected in terms of nature, severity, or frequency given (a) the research 
procedures that are described in the protocol-related documents, such as the 
Institutional Review Board (IRB)-approved research protocol and informed consent 
document; and (b) the characteristics of the participant  population being studied;  

           
 
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• 
Related or possibly related to participation in the research (“possibly related” means 
there is a reasonable possibility that the incident, experience, or outcome may have 
been caused by the procedures involved in the research); and  
• 
Suggests that the research places participants  or others at a greater risk of harm 
(including physical, psychological, economic, or social harm) than was previously 
known or recognized.  
Notification to Regulatory Authorities and IRBs  
The Investigator or designee will report UAPs to the IRB per required timelines, and the 
Sponsor will notify the FDA as applicable. 
9.5.6 
Serious Adverse Event Follow-Up 
The Investigator or designee will continue to follow all AEs and SAEs until the completion of 
the study (Week 14). All communication between the Investigator or designated study team 
members and participants regarding the treatment and outcome of the AE will be documented 
and included as part of the study database.  
If a participant is withdrawn at any stage during the study due to an AE, the Investigator or 
designee will advise the participant of appropriate follow-up with a local doctor, if needed. If a 
participant’s involvement in the study ends prior to resolution of an event, the event will be 
marked as ongoing and the Investigator or designee will advise the participant of appropriate 
follow-up (e.g., to provide follow-up information/referral to the participant’s primary care 
physician). The status of the AE at the last follow-up will be documented. 
Notification to Regulatory Authorities and IRBs  
The Investigator or designee will report UAPs to the IRB per required timelines, and the 
Sponsor will notify the FDA as applicable. 
9.5.7 
Pregnancy Reporting 
Participants who self-report pregnancy will be excluded from the study at screening. If the 
participant reports being pregnant after enrollment, they will be withdrawn from the study 
and a Pregnancy Reporting Form will be filled out by the PI or designee and the Sponsor will 
be alerted of the pregnancy. Participants that become pregnant after enrollment and have 
taken at least one dose of Qelbree, will be followed until the outcome of the pregnancy is 
known. 
10. 
Study 
Completion 
and 
Discontinuation 
10.1 Study Completion 
Participants that take study medication until Week 14/EOS and complete most study 
procedures (e.g. safety and ClinROs) by the end of the 14-week treatment period will be 

           
 
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considered to have completed the study. Participants that choose to discontinue study 
medication prior to Week 14, will be withdrawn from the study and reasons for 
discontinuation will be noted in the eCRF. 
10.2 Study Discontinuation 
The participant may withdraw themselves from the study at any time by notifying the study 
team. Participants may be discontinued from the study by the Investigator or designee if 
study procedures have not been followed or if the Investigator or designee determines the 
participant is not able to safely continue with the study due to an AE or other health-related 
issue. 
Reasons for participant’s study discontinuation may include:  
• 
Withdrawal of consent (the reason for withdrawal of consent should be captured) 
• 
Adverse event(s) 
• 
Lack of efficacy 
• 
Noncompliance with study procedures  
• 
Lost to follow-up (the Investigator will document efforts to attempt to reach the 
participant by phone, email, and chat via study mobile app prior to considering that 
participant lost to follow-up) 
• 
Other 
After a participant has been discontinued, they will not be allowed to re-screen for 
enrollment in the study, unless there is a technical issue. The reasons for discontinuation will 
be documented in the participant’s study record. Participants enrolled in error may be 
discontinued from the study with agreement from the Investigator and Sponsor. 
If a participant is discontinued for any reason other than lost to follow-up, Week 14 
procedures should be completed, and any outstanding data recorded in their record. If a 
participant is withdrawn at any stage during the study due to an AE, the Investigator or 
designee will advise the participant of appropriate follow-up with a local doctor, if needed. If 
a participant’s involvement in the study ends prior to resolution of an event, the event will be 
marked as ongoing and the Investigator or designee will advise the participant of 
appropriate follow-up (e.g., to provide follow-up information/referral to the participant’s 
primary care physician). The status of the AE at the last follow-up will be documented. The 
reason for discontinuation and efforts to follow participants who discontinue because of AEs 
will be fully documented. 
10.3 Lost to Follow-up 
A participant can be considered lost to follow-up if they fail to comply with scheduled visits 
and are unable to be contacted by the Investigator or designated study personnel on three 
separate documented attempts. The date of study termination will be the last scheduled visit 
contact with the participant. If, at any point, contact is re-established with the participant, they 

           
 
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may be allowed to continue in the study at the discretion of the Investigator and with prior 
written approval from the Sponsor. 
11. 
Data Management 
11.1 Data Collection 
Study data will be collected in the study mobile app and study’s Electronic Data Capture 
(EDC) Platform.  
All questionnaire responses/assessment ratings will be directly captured in the study’s EDC 
platform, with the exception of the MINI-AS that is completed separately, and select portions 
are captured in the study’s EDC platform.  
Management of clinical data will be performed in accordance with applicable standards and 
procedures with oversight by the Sponsor to ensure integrity of the data. 
To protect the privacy of participants, no personal information [including the name(s) or 
initial(s)] is to be recorded in the eCRF or as part of the query text. Identifiable data are 
isolated to specific members of the study team and these data will not be 
transferred/available to the Sponsor. 
The Sponsor will be provided with all associated study data, as applicable, at the completion 
of the study. 
11.2 Data Handling 
Documentation of all data management activities should allow step-by-step retrospective 
assessment of data quality and study performance. Any changes or corrections to data will be 
performed in the study’s EDC Platform, and it will include rationale for changes. The EDC 
system has an audit trail, which will provide a complete record of the changes and 
corrections endorsed by the Investigator.  
The study mobile app and associated management system  are fully validated and 21 CFR 
Part 11 complaint. Release notes and validation certificates are held by CRO. 
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
and any concomitant medications terms (if applicable) will be coded using the medication 
dictionary, WHODrug. 
11.3 Data Entry 
Once consent is obtained, the participants will complete the required information via the 
study mobile app. In addition to the participant entered information, the decentralized site 
staff will be entering data into an EDC. 
11.4 Computerized Logical Checks 

           
 
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The database will incorporate the needed programmed logical checks to ensure consistent 
and complete data entry. The data management team will perform logical manual checks, 
and queries will be raised for the decentralized site staff to address. 
11.5 Audit Trail 
The Clinical Data Management System complies with Good Clinical Practice (GCP) 
predicated rule requirements, laws, and regulations (Personal data protection) for clinical 
trials and allows an audit of actions performed by users.  
All original entries and changes made in the database will be captured by an audit trail which 
will include the date and time of the entry or change, and the individual making the entry or 
change who will be identified via their unique user ID. 
12. Statistical Methods 
12.1 General Considerations 
All statistical analysis will be performed using SAS version 9.4 or higher or R version 4.03 or 
higher. All statistical analyses will be presented using descriptive statistics. Summary statistics 
for continuous variables will include sample size (N), mean, median, standard deviation, first 
quartile (Q1), third quartile (Q3), minimum, and maximum. Summary statistics for categorical 
variables will be presented in terms of frequencies and percentages. Participant data listing 
to support summaries will be provided. More details will be provided in the Statistical 
Analysis Plan (SAP). 
Baseline is defined as the last non-missing assessment recorded before receiving the first 
dose of study medication.  
12.2 Populations for Analyses 
Safety Analysis Set: This set includes all participants who provided informed consent and 
took at least one dose of Qelbree. The safety analyses will be conducted using the Safety 
Analysis Set. Safety data will be summarized based on the Safety Analysis Set.  
Efficacy Analysis Set: For each secondary efficacy outcome measure, the summary will be 
based on a subset of participants in the Safety Analysis Set who have a valid AISRS at baseline 
(prior to first dose) and at least one valid AISRS post-baseline (following first dose) 
assessment. 
12.3 Determination of Sample size 
Up to 750 participants will be dosed in this study, to obtain up to 500 competed (through the 
end of Week 14 of treatment) participants, with an anticipated attrition rate of 33%. There is 
no consideration for power for the sample size determination in this decentralized, open 
label study.  

           
 
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12.4 Patient Disposition 
The number and percentage of participants in the Safety Analysis Set, the Efficacy Analysis 
Set, who completed the study and discontinued from the study and the primary reason for 
early discontinuation will be summarized. 
12.5 Demographics and Baseline Analysis 
Demographic/baseline variables will be presented in descriptive summaries that include age, 
age group, sex, ethnicity, race, height and weight at baseline, BMI, and other baseline 
efficacy end points using descriptive statistics for continuous variables and using counts and 
percentages for categorical variables.  
12.6 Study Medication Exposure and Compliance 
Duration of exposure is defined as the total number of days a patient is exposed to Qelbree. 
This will be calculated for each patient by taking the difference between the date of last dose 
minus the date of the first dose, plus 1 (date of last dose minus date of first dose +1). 
Duration of SM exposure will be summarized by duration category (defined in the SAP) and 
will also be summarized using descriptive statistics. 
Percent of SM compliance is defined as {(number of capsules dispensed minus number of 
capsules returned) /number of capsules instructed to take * 100%. SM compliance will be 
summarized by compliance category (<80%, 80-120%, and >120%) and number and percent 
of participants in each compliance category. Study medication compliance will also be 
summarized as a continuous variable using descriptive statistics. 
12.7 Concomitant Medications 
Concomitant medications will be assigned an 11-digit code using the WHO-DD drug codes. 
Concomitant medications will be further coded to the appropriate Anatomical-Therapeutic-
Chemical (ATC) code indicating therapeutic classification. A tabular summary of concomitant 
medications by drug class will be presented for the Safety population. 
12.8 Efficacy Analysis 
12.8.1 Primary Endpoint(s) 
• 
The primary efficacy endpoint is change from baseline in AISRS Total score by visit. 
The observed (raw) and change from baseline Total score will be summarized by 
study visit using descriptive statistics as described above. The summary will be based 
on Efficacy Analysis Set.  
12.8.2 Secondary Endpoint(s) 
The following secondary endpoints will be analyzed in a similar manner to the primary 
endpoint. 

           
 
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• 
Change from baseline in AISRS Inattention and Hyperactivity/Impulsivity Subscale 
scores by visit 
• 
Change from baseline in ASRSv1.1-SC Total score by visit 
• 
Change from baseline in ASRSv1.1-SC Subscale (Inattention and 
Hyperactivity/Impulsivity) scores by visit 
• 
Change from baseline CGI-S score by visit 
• 
CGI-C score by visit 
• 
Change from baseline in MADRS Total Score at Week 14/EOS 
• 
Change from baseline in PHQ-8 Total Score by visit 
• 
Change from baseline in HAM-A Total Score at Week 14/EOS 
• 
Change from baseline in GAD-7 Total Score by visit 
• 
Change from baseline at Week 14/EOS in BRIEF-A T-score for the:  
i. Global Executive Composite (GEC) 
ii. Behavioral Regulation Index (BRI) 
iii. Metacognition Index (MI) 
• 
Change from baseline in the WPAI:SHP absenteeism percentage by visit, 
presenteeism percentage by visit, work productivity percentage by visit, and regular 
activity percentage by visit 
• 
Change from baseline at Week 14/EOS in the PSQI global score  
 
The observed (raw) and the change from baseline (except CGI-C) score/value will be 
summarized by study visit for each secondary efficacy outcome measure (total/global score 
and subscale scores) using descriptive statistics as described above. For each secondary 
efficacy outcome measure, the summary will be based on Efficacy Analysis Set. 
12.9 Safety Analysis 
Safety analyses will be performed based on the safety analysis set. 
AEs will be classified into standardized medical terminology from the Verbatim description 
(Investigator term) using the Medical Dictionary for Regulatory Activities (MedDRA) and 
Preferred Term (PT). 
The incidence rate, severity, and relationship to Qelbree for all AEs will be summarized for 
each System Organ Class (SOC) and PT. The absolute and change from baseline for blood 
pressure, pulse rate, and weight will be presented will be summarized using descriptive 
statistics by study visit. 
Columbia Suicide Severity Rating Scale (C-SSRS) outcomes will be summarized using number 
and percent of participants by categories for suicidal ideation, suicidal behavior and suicidal 
ideation or behavior. 
12.10 Exploratory Analysis 

           
 
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13. 
Quality Control and Assurance 
13.1 Acceptability of Case Report Forms (Source Documents) 
A case report form (CRF) is a printed, optical, or electronic document designed to record the 
protocol required information to be reported to the sponsor on each trial participant.  
Management of clinical data will be performed in accordance with CRO’s applicable 
standards and procedures with oversight from the Sponsor to ensure integrity of the data.  
To protect the privacy of participants, no personal information (including the name or initials) 
is to be recorded in the eCRF or as part of the query text.  
All eCRF pages should be completed during a participant’s assessment when the eCRF has 
been designated as the source. 
The Sponsor will obtain and retain all eCRFs and associated study data as applicable at the 
completion of the study.  
Any identifiable data accessible to a designated team at CRO will not be transferred/available 
to the Sponsor except if needed during routine monitoring, regulatory audit, and/or 
inspection.  
Before enrolling any participants in the study, the Sponsor or its designee and the 
Investigator will review the protocol, the eCRF and eCRF instructions, the procedure for 
obtaining informed consent, and the procedure for reporting AEs. 
13.2 Modification of Protocol 
All additions or changes to the study protocol must be approved by the Sponsor. The IRB 
must be notified of all subsequent additions or changes in the study protocol for review and 
approval as necessary.  
The Investigator will not make any changes to this protocol without prior written consent from 
the Sponsor and the subsequent approval by the IRB. Any permanent change to the protocol, 
whether it is an overall change or a specific change, must be handled as a protocol 
amendment. The written amendment must be submitted to the chairperson of the IRB 
identified with this responsibility. Except for ‘’administrative amendment’’, Investigators must 

           
 
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await IRB approval of protocol amendments before implementing the change(s). 
Administrative amendments are defined to have no effect on the safety of the research 
participants, scope of the investigation, or quality of the trial. However, a protocol change 
intended to eliminate an apparent immediate hazard to participants should be implemented 
immediately, and the IRB notified as per stipulated timeline within five days.  
When, in the judgment of the reviewing IRB, the Investigators and/or Sponsor, the 
amendment to the protocol substantially alters the study design and/or increases the 
potential risk to the participant, the currently approved written informed consent form will 
require similar modification. In such cases, informed consent will be re-obtained from 
participants enrolled in the study before expecting continued participation. 
13.3 Reporting Protocol Deviations 
A protocol deviation is any non-compliance with the clinical study protocol or International 
Conference on Harmonization Good Clinical Practice (ICH GCP). The non-compliance may be 
either on the part of the participant, the Investigator, or the study staff. It is the responsibility 
of the Investigator to identify and report deviations per IRB requirements. 
13.4 Monitoring 
This study will be monitored on an ongoing basis.  
The Sponsor or its designated study monitor may perform ongoing review of the eCRFs in 
accordance with the monitoring plan, to confirm that data entered into the eCRF by 
authorized site personnel is accurate, complete, and verifiable from source documents (as 
applicable); that the safety and rights of participants are being protected; and that the study 
is being conducted in accordance with the currently approved protocol and any other study 
agreements, ICH GCP, and all applicable regulatory requirements. At the end of the trial the 
monitor will make a study site close-out visit to ensure that all documentation is complete. In 
all cases, it is the responsibility of the CPM / monitor to maintain participant confidentiality. 
13.5 Audits and Inspections 
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor may 
conduct a quality assurance assessment and/or audit of the study records, and the regulatory 
agencies may conduct a regulatory inspection at any time during or after completion of the 
study.  
In the event of an assessment, audit, or inspection, CRO will grant advisor(s), auditor(s), and 
inspector(s) access as per agreed upon terms to relevant documents and to allocate their 
time and the time of their staff to discuss the conduct of the study, any findings/relevant 
issues and to implement any corrective and/or preventative actions to address any 
findings/issues identified. 

           
 
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CRO will notify the Sponsor or its agents immediately of any regulatory inspection notification 
in relation to the study.  
The Sponsor will be available to help CRO prepare for an inspection. 
14. 
 Ethics and Regulatory Requirements 
14.1 Institutional Review Board/Independent Ethics Committee 
The study protocol will be submitted by the Investigator for examination by the IRB. 
Commencement of the clinical study is not permitted without written approval of the IRB. 
The study will be initiated after approval from the IRB which follows the guidance of US 
regulatory bodies, general GCP regulations, and standards set by the ICH. 
This study will be conducted according to the principles and rules laid down in the 
Declaration of Helsinki and its subsequent amendments. 
14.2 Investigator Responsibilities 
The Investigator or designee is responsible for the following: 
• 
Obtaining the written and dated approval of the applicable IRB and other regulatory 
agency, if any, prior to the conduct of the study 
• 
Selecting participants in accordance with the inclusion and exclusion criteria after the 
eIC is signed 
• 
Maintaining confidentiality and safety of participants in accordance with the 
Declaration of Helsinki 
• 
Adhering to the study protocol and the spirit of GCP 
• 
Following procedure if modification becomes necessary. The PI or designee will 
provide a rationale in a protocol amendment, which is signed by the Investigator and 
Sponsor for submission to the IRB. After the protocol amendment approval, 
participants still active in the study must re-sign the eIC to remain in the study 
• 
Providing accurate, complete, and timely data reported to the Sponsor  
• 
Providing participants with any newly available information that may be relevant to 
them during the study 
• 
Identifying AEs and notifying the Sponsor, IRB, and health authorities, as applicable 
• 
Cooperating in the case of an audit and/or regulatory inspections, providing direct 
access to data and/or documents. 
14.3 Informed Consent Process 
Informed consent will be obtained from the participants using the IRB-approved electronic 
Informed Consent (eIC) method before any study-related procedures are performed or any 
data are collected and will be done in accordance with all applicable regulatory 
requirements. 

           
 
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The informed consent form (ICF) used during the informed consent process must be the 
current IRB approved ICF. The IRB/Ethics Committee (EC) will approve the eIC language. Any 
amendments to these documents must be approved by the IRB/EC prior to distribution or 
use. 
Before any protocol-required procedures are performed, the participant must: 
• 
Be informed of all aspects of the study (risks and benefits) 
• 
Be given time to ask questions and time to consider the decision to participate 
• 
Voluntarily agree to participate in the study  
• 
Sign and date an IRB approved eIC 
The Investigator and/or designee will be available to answer questions about all aspects of 
the study before the participant decides they want to participate.  
The decision of the participant to participate in the study is entirely voluntary. It will be clearly 
stated to the participant within the eIC language that the consent to participate can be 
withdrawn at any time without penalty or loss of benefits to which the participant is otherwise 
entitled. 
15. 
 Study Closure 
Premature Termination of Study 
Should it prove necessary to discontinue the study permanently prior to completion, the 
Sponsor will notify CRO and the IRB of the rationale. Participants will be informed by CRO or 
its designee. All relevant study documents and data will then be returned to the Sponsor. 
Termination of Study 
After the completion or termination of the study, all relevant study documents and data will 
be sent to the Sponsor by the CRO. The Investigator will inform the IRB of the end of the 
study and a certificate of study closure will be issued. 
16. 
 Publication Plan 
Any presentation or publication of data collected as a direct or indirect result of this trial will 
be considered as a joint publication by the Investigator(s) and the appropriate personnel at 
the Sponsor’s site. Authorship will be determined by mutual agreement. All manuscripts, 
abstracts or other modes of presentation arising from the results of the study must be 
reviewed and approved in writing by the Sponsor, prior to submission for publication or 
presentation. No publication or presentation with respect to the study shall be made until all 
Sponsor comments on the proposed publication or presentation have been addressed to the 
Sponsor’s satisfaction. 

           
 
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The detailed obligations regarding the publication of any data, material results, or other 
information, generated or created in relation to the study shall be outlined in the agreement 
between each Investigator and the Sponsor or designee. 
 
 

           
 
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17. 
 References 
Abdelnour E, Jansen MO, Gold JA. ADHD Diagnostic Trends: Increased Recognition or 
Overdiagnosis? Mo Med. 2022 Sep-Oct;119(5):467-473. 
Adler LA, Clemow DB, Williams DW, Durell TM. Atomoxetine Effects on Executive Function as 
Measured by the BRIEF-A in Young Adults with ADHD: A Randomized, Double-Blind, 
Placebo-Controlled Study. PLoS One. 2014 Aug 22;9(8):e104175. 
Adler LA, Faraone SV, Sarocco P, Atkins N, Khachatryan A. Establishing US norms for the 
Adult ADHD Self-Report Scale (ASRS-v1.1) and characterizing symptom burden among 
adults with self-reported ADHD. Int J Clin Pract. 2019;73(1):e13260. 
Adler LA, Spencer T, Faraone SV, Kessler RC, Howes MJ, Biederman J, Secnik K. Validity of 
pilot Adult ADHD Self- Report Scale (ASRS) to rate adult ADHD symptoms. Ann Clin 
Psychiatry. 2006;18(3):145-148. 
Attention-Deficit/Hyperactivity Disorder (ADHD). NIH. Available online: 
https://www.nimh.nih.gov/health/statistics/attention-deficit-hyperactivity-disorder-adhd 
(Accessed on 26JUL2023). 
Biederman J, Monuteaux MC, Spencer T, Wilens TE, Faraone SV. Do stimulants protect 
against psychiatric disorders in youth with ADHD? A 10-year follow-up study. Pediatrics. 
2009;124(1):71–78. 
Borkovec T and Costello E. Efficacy of applied relaxation and cognitive behavioral therapy in 
the treatment of generalized anxiety disorder. J Clin Consult Psychol. 1993;61(4):611-
619. 
Buysse DJ, Reynolds CF III, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality 
Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 
May;28(2):193-213. 
Faraone SV, Banaschewski T, Coghill D, Zheng Y, et al. The World Federation of ADHD 
International Consensus Statement: 208 Evidence-based conclusions about the disorder. 
Neurosci Biobehav Rev. 2021;128:789-818. 
Findling RL, Candler SA, Nasser AF, Schwabe S, Yu C, Garcia-Olivares J, O'Neal W, Newcorn 
JH. Viloxazine in the Management of CNS Disorders: A Historical Overview and Current 
Status. CNS Drugs. 2021 Jun;35(6):643-653. 
Groom MJ and Cortese S. Current Pharmacological Treatments for ADHD. Curr Top Behav 
Neurosci. 2022;57:19-50. 
Guy W, 1976. Clinical global impressions. ECDEU Assessment manual for 
Psychopharmacology, Rockville, MD: US National Institutes of Health, 
Psychopharmacology Research Branch. 
Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. 1959;32:50-55. 
Herrmann N, Black S, Lawrence J, Szekely C, Szalai J. The Sunnybrook stroke study: A 
prospective study of depressive symptoms and functional outcomes. Stroke. 1998; 
29:618-624. 

           
 
Protocol 812P413 
Page 
57 of 61 
Version  
2.0  
 
CONFIDENTIAL – DO NOT DISTRIBUTE 
Johnson JK, Liranso T, Saylor K, Tulloch G, Adewole T, Schwabe S, Nasser A, Findling RL, 
Newcorn JH. A Phase II Double-Blind, Placebo-Controlled, Efficacy and Safety Study of 
SPN-812 (Extended-Release Viloxazine) in Children With ADHD. J Atten Disord. 2020 
Jan;24(2):348-358. 
Katzman MA, Bilkey TS, Chokka PR, Fallu A, Klassen LJ. Adult ADHD and comorbid disorders: 
clinical implications of a dimensional approach. BMC Psychiatry. 2017 Aug 22;17(1):302. 
Kessler RC, Adler L, Ames M, Demler O, Faraone S, Hiripi E, et al. The World Health 
Organization Adult ADHD Self-Report Scale (ASRS): a short screening scale for use in the 
general population. Psychol Med. 2005;35(2):245-256. 
Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, Faraone SV, Greenhill LL, 
Howes MJ, Secnik K, Spencer T, Ustun TB, Walters EE, Zaslavsky AM. The prevalence and 
correlates of adult ADHD in the United States: results from the National Comorbidity 
Survey Replication. Am J Psychiatry. 2006 Apr;163(4):716-723.  
Kolar D, Keller A, Golfinopoulos M, Cumyn L, Syer C, Hechtman L. Treatment of adults with 
attention-deficit/hyperactivity disorder. Neuropsychiatr Dis Treat. 2008 Apr;4(2):389-403. 
Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity 
measure. J Gen Intern Med. 2001 Sep;16(9):606-613. 
Kroenke K, Strine TW, Spitzer RL, Williams JB, Berry JT, Mokdad AH. The PHQ-8 as a measure 
of current depression in the general population. J Affect Disord. 2009 Apr;114(1-3):163-
173. 
Lecrubier Y, Sheehan D, Weiller E, Amorim P, Bonora I, Sheehan K, Janavs J, Dunbar G. The 
MINI International Neuropsychiatric Interview (M.I.N.I.) A Short Diagnostic Structured 
Interview: Reliability and Validity According to the CIDI. European Psychiatry. 1997;12: 
224-231. 
Lee L, Arunajadai S, Mikl J, Erensen JG, Goodman DW. The Burden of Attention-
Deficit/Hyperactivity Disorder in Adults: A Real-World Linked Data Study. Prim Care 
Companion CNS Disord. 2023 Mar 14;25(2):22m03348. 
Magnin E and Maurs C. Attention-deficit/hyperactivity disorder during adulthood. Rev Neurol 
(Paris). 2017 Jul-Aug;173(7-8):506-515. 
Maier W, Buller R, Philipp M, Heuser I. The Hamilton Anxiety Scale: reliability, validity and 
sensitivity to change in anxiety and depressive disorders. J Affect Disord. 1988;14(1):61-
68. 
Montgomery SA and Asberg M. A new depression scale designed to be sensitive to change. 
Br J Psychiatry. 1979;134(4):382-389. 
Müller MJ, Szegedi A, Wetzel H, Benkert O. Moderate and severe depression. Gradations for 
the Montgomery-Asberg Depression Rating Scale. J Affect Disord. 2000 Nov;60(2):137-
140. 
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 

           
 
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CONFIDENTIAL – DO NOT DISTRIBUTE 
of Attention-deficit/Hyperactivity Disorder in School-age Children. Clin Ther. 2020 
Aug;42(8):1452-1466. 
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. 2021a 
Apr;43(4):684-700.  
Nasser A, Liranso T, Adewole T, Fry N, Hull JT, Busse GD, Chowdhry F, Cutler AJ, Jones NJ, 
Findling RL, Schwabe S. A Phase 3, Placebo-Controlled Trial of Once-Daily Viloxazine 
Extended-Release Capsules in Adolescents With Attention-Deficit/Hyperactivity Disorder. 
J Clin Psychopharmacol. 2021b;41(4):370-380. 
Nasser A, Liranso T, Adewole T, Fry N, Hull JT, Chowdhry F, Busse GD, Melyan Z, Cutler AJ, 
Findling RL, Schwabe S. A Phase 3 Placebo-Controlled Trial of Once-Daily 400-mg and 
600-mg SPN-812 (Viloxazine Extended-Release) in Adolescents with ADHD. 
Psychopharmacol Bull. 2021c Mar 16;51(2):43-64. 
Nasser A, Hull JT, Chaturvedi SA, Liranso T, Odebo O, Kosheleff AR, Fry N, Cutler AJ, Rubin J, 
Schwabe S, Childress A. A Phase III, Randomized, Double-Blind, Placebo-Controlled Trial 
Assessing the Efficacy and Safety of Viloxazine Extended-Release Capsules in Adults with 
Attention-Deficit/Hyperactivity Disorder. CNS Drugs. 2022 Aug;36(8):897-915. 
Pawaskar M, Fridman M, Grebla R, Madhoo M. Comparison of Quality of Life, Productivity, 
Functioning and Self-Esteem in Adults Diagnosed With ADHD and With Symptomatic 
ADHD. J Atten Disord. 2020 Jan;24(1):136-144. 
Posner K, Brown GK, Stanley B, Brent DA, Yershova KV, Oquendo MA, Currier GW, Melvin 
GA, Greenhill L, Shen S, Mann JJ. The Columbia-Suicide Severity Rating Scale: initial 
validity and internal consistency findings from three multisite studies with adolescents and 
adults. Am J Psychiatry. 2011 Dec;168(12):1266-1277. 
Qelbree® (viloxazine extended-release capsules), for oral use. Prescribing Information.  
Qelbree® For US Healthcare Professionals only. Available online: 
https://www.qelbreehcp.com/efficacy/adults (Accessed on 26JUL2023). 
Reilly MC, Zbrozek AS, Dukes EM. The validity and reproducibility of a work productivity and 
activity impairment instrument. Pharmacoeconomics. 1993 Nov;4(5):353-365. 
Roth R. M., Isquith P. K., Gioia G. A. Behavior Rating Inventory of Executive Function - Adult 
Version (BRIEF-A) Lutz, FL: Psychological Assessment Resources; 2005. 
Roth RM, Lance CE, Isquith PK, Fischer AS, Giancola PR. Confirmatory factor analysis of the 
Behavior Rating Inventory of Executive Function-Adult version in healthy adults and 
application to attention-deficit/hyperactivity disorder. Arch Clin Neuropsychol. 2013 
Aug;28(5):425-434. 
Schein J, Cloutier M, Gauthier-Loiselle M, Bungay R, Guerin A, Childress A. Symptoms 
associated with ADHD/treatment-related adverse side effects and their impact on quality 
of life and work productivity in adults with ADHD. Curr Med Res Opin. 2023 
Jan;39(1):149-159. 

           
 
Protocol 812P413 
Page 
59 of 61 
Version  
2.0  
 
CONFIDENTIAL – DO NOT DISTRIBUTE 
Shear MK, Vander Bilt J, Rucci P, Endicott J, Lydiard B, Otto MW, Pollack MH, Chandler L, 
Williams J, Ali A, Frank DM. Reliability and validity of a structured interview guide for the 
Hamilton Anxiety Rating Scale (SIGH-A). Depress Anxiety. 2001;13(4):166-178.  
Sheehan DV, Lecrubier Y, Harnett-Sheehan K, Janavs J, Weiller E, Bonara LI, Keskiner A, 
Schinka J, Knapp E, Sheehan MF, Dunbar GC. Reliability and Validity of the MINI 
International Neuropsychiatric Interview (M.I.N.I.): According to the SCID-P. European 
Psychiatry. 1997; 12:232-241. 
Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, 
Dunbar GC. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development 
and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J 
Clin Psychiatry. 1998;59 Suppl 20:22-33;quiz 34-57. 
Snaith R, Harrop F, Newby D, Teale C. Grade scores of the Montgomery- Åsberg Depression 
and the Clinical Anxiety Scales. Brit J Psychiatry. 1986 May; 148:599-601. 
Spalding W, Farahbakhshian S, Maculaitis MC, Peck EY, Goren A. The Association of Oral 
Stimulant Medication Adherence with Work Productivity among Adults with ADHD. J 
Atten Disord. 2022 Apr;26(6):831-842. 
Spencer TJ, Adler LA, Meihua Q, Saylor KE, Brown TE, Holdnack JA, Schuh KJ, Trzepacz PT, 
Kelsey DK. Validation of the adult ADHD investigator symptom rating scale (AISRS). J 
Atten Disord. 2010 Jul;14(1):57-68. 
Spitzer RL, Kroenke K, Williams JB, Löwe B. A brief measure for assessing generalized anxiety 
disorder: the GAD-7. Arch Intern Med. 2006 May 22;166(10):1092-1097. 
Spitzer RL, Kroenke K, Williams JB. Validation and utility of a self-report version of PRIME-MD: 
the PHQ primary care study. Primary Care Evaluation of Mental Disorders. Patient Health 
Questionnaire. JAMA. 1999 Nov 10;282(18):1737-1744. 
Spitzer RL, Williams JB, Kroenke K, Hornyak R, McMurray J. Validity and utility of the PRIME-
MD patient health questionnaire in assessment of 3000 obstetric-gynecologic patients: 
the PRIME-MD Patient Health Questionnaire Obstetrics-Gynecology Study. Am J Obstet 
Gynecol. 2000 Sep;183(3):759-769. 
Weibel S, Menard O, Ionita A, Boumendjel M, Cabelguen C, Kraemer C, Micoulaud-Franchi 
JA, Bioulac S, Perroud N, Sauvaget A, Carton L, Gachet M, Lopez R. Practical 
considerations for the evaluation and management of Attention Deficit Hyperactivity 
Disorder (ADHD) in adults. Encephale. 2020 Feb;46(1):30-40. 
Williams JBW and Kobak KA. Development and reliability of a structured interview guide for 
the Montgomery– Åsberg Depression Rating Scale (SIGMA). Brit J Psychiatry. 2008 Jan; 
192:52-58. 
 
 

           
 
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