Efficacy of Centanafadine SR as a Potential Smoking Cessation Treatment

This study will explore the efficacy and tolerability of centanafadine at a dose of 400 mg per day of centanafadine in promoting smoking abstinence in adult smokers seeking to quit.

This single-group, open-label study of 50 participants will explore the potential of centanafadine in promoting smoking abstinence in adult smokers seeking to quit. The efficacy and tolerability of centanafadine at a dose of 400 mg total daily dose (TDD) (200 mg twice a day (BID)) approximately 4 to 6 hours apart (during a 7-week treatment period) will be compared with a benchmark of abstinence based on historical data from clinical trials of varenicline, viewed as the most efficacious pharmacotherapy currently approved by the FDA.

Eligibility Criteria:
Inclusion Criteria:

1. Has signed the informed consent form (ICF) and is able to read and understand the information provided in the ICF.
2. Smokers 21 to 65 years of age (inclusive) at screening.
3. Smokes an average of at least 10 commercially available cigarettes per day for the last 12 months.
4. Has an expired air carbon monoxide (CO) reading of at least 10 ppm at screening.
5. At screening, express a desire to quit smoking within the next 30 days.
6. Body mass index (BMI) of 18 to 40 kg/m2, inclusive at screening.
7. Willing and able to comply with the requirements of the study.
8. Owns a smartphone with text message and data capabilities compatible with necessary surveys.

Exclusion Criteria:

1. Participants of childbearing potential (CBP) who are breastfeeding and/or have a positive pregnancy test result.
2. Participant presenting with, or having a history of, uncontrolled hypertension (systolic blood pressure \>150 mmHg or diastolic blood pressure \> 95 mmHg) or symptomatic hypotension.
3. Participants with known ischemic heart disease or history of myocardial infarction, congestive heart failure (whether controlled or uncontrolled), angioplasty, stenting, coronary artery bypass surgery, or other serious cardiac problems that would place him/her at increased vulnerability to the sympathomimetic effects of stimulant medication.
4. History of seizures (after the age of 17 years).
5. Participants of CBP or sexually active participants unless they agree to practice 2 different methods of birth control or remain abstinent during the course of the trial and for 30 days after the last dose of Investigation Medicinal Product (IMP) for participants of CBP, and 30 days after the last dose of IMP for participants with partners who are of CBP. Unless the participant is sterile (i.e., participants who have had a bilateral oophorectomy or hysterectomy or who have been postmenopausal for at least 12 consecutive months; or participants who have had a bilateral orchidectomy) or remains abstinent, 2 of the following precautions must be used: vasectomy, tubal ligation, vaginal diaphragm, intrauterine device, birth control pills, birth control injection, birth control implant, birth control patch, condom with spermicide, or sponge with spermicide. Participants who do not agree to refrain from donating sperm from screening through 30 days after the last dose of IMP.
6. Participant has a history of dermatologic adverse reactions secondary to any drug exposure or any active/uncontrolled dermatologic disease.
7. Currently taking antidepressants (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), Tricyclic antidepressants (TCAs), or monoamine oxidase inhibitors (MAOIs)), antipsychotics (such as butyrophenones, thioxanthenes, atypical antipsychotics or other heterocyclics), benzodiazepines, hypnotics, or medications that prolong corrected QT Interval (QTc). MAOI's taken within 30 days of screening.
8. Screening (Visit 1) or Baseline (Visit 2) Columbia-Suicide Severity Rating Scale (C-SSRS) score greater than 0 (any answer "Yes") for the SUICIDAL IDEATION section or greater than 0 for the SUICIDAL BEHAVIOR section (any answer "Yes").
9. Substance use disorder within 12 months prior to screening.
10. Participants that have a positive alcohol test (via breathalyzer or blood), a positive drug screen for illicit drugs (Table 6.3.5) at screening or baseline.

    Participants who test positive for marijuana at screening may be enrolled if they have no evidence of a substance use disorder and if they agree to refrain from use for the duration of the trial.
11. Any participant who has any other medical or physical condition(s) that, in the opinion of the investigator, may prevent the participant from completing the trial or would go against the participant's best interest with participation in the trial. This would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol.
12. Participants with abnormal laboratory tests, vital sign results, or ECG findings which in the investigator's judgment are medically significant and that would impact the safety of the participant or the interpretation of the trial results.
13. Participants with a history of prior exposure to centanafadine.
14. Use of smokeless tobacco (chewing tobacco, snuff), cigars (except for "Black \& Mild" cigars or Cigarillos), pipes, hookah, e-cigarettes, nicotine replacement therapy, or other smoking cessation treatments (e.g., bupropion as Zyban, or varenicline) within 14 days of screening.
15. Participants who participated in a clinical trial and were exposed to interventional trial medication within the last 30 days prior to screening or who participated in more than 2 interventional clinical trials within the past year.