Safety and Efficacy Study of Centanafadine Sustained-Release (CTN SR) in Adults With Attention-Deficit Hyperactivity Disorder (ADHD)

Inclusion Criteria:

1. Participant is 18 to 60 years of age, inclusive, at the time of consent

2. Participant meets Diagnostic and Statistical Manual of Mental Disorders, Fifth
Edition (DSM-5) criteria for a primary diagnosis of ADHD, any presentation,
established by a comprehensive psychiatric evaluation based on DSM-5 criteria with at
least 5 of the 9 subtype criteria met, as determined by the Conners' Adult ADHD
Diagnostic Interview for Diagnostic and Statistical Manual of Mental Disorders,
Fourth Edition (DSM-IV) (CAADID Part II)

3. Participant has a Baseline score of greater than or equal to 28 using the ADHD-RS-IV

4. Participant has a minimum score of 4 on the CGI-S at Baseline

5. Participant is functioning at an age-appropriate level intellectually, as judged by
the Investigator

Exclusion Criteria:

1. Participant has a current comorbid psychiatric disorder that is either controlled
with medications prohibited in this study or is uncontrolled and associated with
significant symptoms. Exclusionary conditions include any severe comorbid Axis II
disorder or severe Axis I disorder (such as post-traumatic stress disorder [PTSD],
psychosis, bipolar illness, severe obsessive compulsive disorder, severe depressive
or severe anxiety disorder) or other symptomatic manifestations that, in the opinion
of the examining physician, will contraindicate CTN SR treatment or confound efficacy
or safety assessments. Specifically, participants with mild to moderate forms of Axis
I disorders (e.g., social phobia and dysthymia) may be included, whereas participants
with a lifetime history of psychosis or bipolar disorder will be excluded. Comorbid
psychiatric diagnosis will be established by a Semi-Structured Clinical Interview for
DSM-5 Axis I Disorders (the Mini lnternational Neuropsychiatric lnterview, Version
6.0 [M.I.N.I. 6.0]).

2. Participants who are currently considered a suicide risk, any participant who had
previously made a suicide attempt, or those who are currently demonstrating active
suicidal ideation as measured by the Columbia-Suicide Severity Rating Scale (C-SSRS)
at Screening, or if in the opinion of the investigator the participant is considered
a suicide risk. Participants who develop suicidal ideation or behavior during the
trial as measured by the C-SSRS will be discontinued and followed appropriately.

3. The participant has a body mass index (BMI) of less than 18.5 or greater than or
equal to 40 at Baseline

4. Participant has a concurrent chronic or acute illness (such as severe allergic
rhinitis or an infectious process requiring antibiotics), disability, or other
condition that might confound the results of safety assessments administered in the
study or that might increase risk to the participant

5. Participant had a history of seizures (other than infantile febrile seizures), any
tic disorder (except transient tic disorder and participant has no episodes greater
than or equal to 1 year), or a current diagnosis and/or a known family history of
Tourette's Disorder (i.e. first degree relatives)

6. Participant has a known history of symptomatic cardiovascular disease, advanced
arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart
rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke or
other serious cardiac problems that may place them at increased vulnerability to
potential sympathomimetic effects

7. Participant has a known family history of sudden cardiac death or ventricular
arrhythmia

8. Participant has a history of significant bleeding or coagulation disorder and/or low
platelet levels (less than 130 X 109/L) or increased international normalized ratio
(INR) (greater than 1.3) at Screening

9. Participant has a history of cancer

10. Participant has any clinically significant 12-lead ECG or clinically significant
laboratory abnormality at Screening and/or Baseline

11. Participant has current abnormal thyroid function, as defined as abnormal Screening
thyroid stimulating hormone (less than 0.34 or greater than 5.6 μIU/mL). Treatment
with a stable dose of thyroid medication for at least 3 months is permitted.

12. Participant has a resting sitting systolic blood pressure (SBP) greater than or equal
to 140 mm Hg or diastolic blood pressure (DBP) greater than or equal to 90 mm Hg. No
more than 1 repeat measurement will be permitted.

13. Participant has a history of hyponatremia

14. Participant is on an antihypertensive medication of any kind

15. Participant has a known history of orthostatic hypotension or has an orthostatic
blood pressure drop of greater than or equal to 20 mm Hg (based on the drop between
sitting and standing [3 minutes] SBP) at Screening or Baseline

16. Participant has a known history of hypertension

17. Participant exhibits lifestyle that may be confounding to safety or efficacy
assessments per the judgment of the investigator (e.g. exercises, diets or travels
extensively)

18. Participant has a known history of glaucoma

19. Participant has failed to respond to 1 or more adequate courses (e.g., adequate dose
and duration with poor response as judged by the Investigator) of stimulant therapy

20. Participant has a recent history (within the past 6 months) of suspected substance
abuse or dependence disorder (excluding nicotine) in accordance with DSM-5 criteria

21. Participant is taking other medications that have central nervous system (CNS)
effects or affect performance, such as sedating antihistamines and decongestant
sympathomimetic, or was recently on monoamine oxidase inhibitors (during or within 14
days of investigational product [IP] administration). Stable use of bronchodilator
inhalers is not exclusionary. This also includes use of any psychoactive prescription
medication within 30 days prior to Screening or psychoactive over-the-counter (OTC)
medication or herbal products that require more than a 7-day washout. Participants
currently treated with methylphenidate or amphetamine products are permitted and will
undergo a 7-day washout period. Participants who have taken atomoxetine will be
required to undergo a 30-day washout.

22. Participant requires the frequent or regular use of aspirin, ibuprofen, and naproxen
sodium, or is on any anticoagulant, such as warfarin

23. Participants taking known potent inhibitors or inducers of common cytochrome P450
(CYP) enzymes, including herbal products

24. Participant has a positive urine drug screen (UDS) result at Screening or Baseline.
NOTE: The UDS must be negative at Screening (with the exception of the participant's
current ADHD psychostimulant, if applicable) or Baseline, if applicable, for the
participant to potentially be eligible for study participation. The Investigator, in
conjunction with the Medical Monitor, will evaluate the potential impact of a
positive UDS regarding the continued participation of the participant.

25. Participant has taken an investigational product or taken part in a clinical study
within 30 days prior to Screening

26. Investigational site personnel are not permitted to participate in the study

27. Participant has participated previously in a CTN investigational study

28. The female participant is pregnant or lactating

29. Participant has a documented allergy, hypersensitivity, or intolerance to CTN or to
any excipients in the reference product

30. Participant has a history of allergy or hypersensitivity to medications (e.g.,
monoamine reuptake inhibitors or antibiotics)

31. Participant does not agree to or is unable to abstain from consuming alcohol during
the study

Reproductive Potential Requirements

32. All female participants are required to have a negative serum beta human chorionic
gonadotropin (HCG) pregnancy test at Screening, a negative urine pregnancy test at
Baseline, and be either postmenopausal (12 consecutive months of spontaneous
amenorrhea and greater than or equal to 51 years of age), surgically sterile and at
least 6 weeks poststerilization or, for females of childbearing potential, have a
negative pregnancy test prior to entering the study and agree to use acceptable
methods of contraception

Contraceptive Requirements

33. Condoms are to be used with all forms of contraception (i.e., double-barrier method).
Acceptable contraceptives include the following:

1. Intrauterine devices

2. Hormonal contraceptives (oral, depot, patch, injectable, or vaginal ring)

3. Diaphragms with spermicidal gel or foam

34. Females of childbearing potential will be advised to use acceptable contraceptives
from the date of informed consent throughout the study period and for the defined
follow-up period

35. If hormonal contraceptives are used, they are to be administered according to the
package insert

36. Females of childbearing potential who are not currently sexually active agree to use
acceptable contraception, as defined above, if they became sexually active during
their study participation and for the defined follow-up time period