Smoking Cessation
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DRUGCentanafadine
400 mg total daily dose Centanafadine Sustained Release, oral tablets
Sponsors
Otsuka Pharmaceutical Development & Commercialization, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With a Continuous Smoking Abstinence Rate | Weeks 4 to 7 | Participants were considered abstinent from combustible cigarettes if the participant self-reported tobacco abstinence (no cigarette smoking, not even a puff) assessed by responses to daily messages throughout Weeks 4-7. Any participants lost to follow-up after receiving the investigational product, or who have smoked during Weeks 4-7 were counted as non-abstinent. The binomial confidence interval was based on normal approximation. If the number of abstinent or the number of non-abstinent ≤ 5, exact method was used. |
| Percentage of Participants With Continuous Smoking Abstinence Rate Determined Based on Expired Air Carbon Monoxide (CO) Reading Assessed Using the Vitalograph Breath CO Monitor | Weeks 4 to 7 | Participants were considered abstinent from combustible cigarettes if the participants had an exhaled CO level of less than 5 parts per million (ppm) measured using the Vitalograph Breath CO monitor. Participants with actual data that they were smoking (CO value ≥ 5 ppm or any smoking record in self-report) were counted as non-abstinent The binomial confidence interval was based on normal approximation. If the number of abstinent or the number of non-abstinent ≤ 5, exact method was used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Nausea | From first dose of study drug to 7 days after receiving last dose (Up to Week 8) | Nausea was only considered when it was a treatment-emergent adverse event (TEAE). A TEAE is defined as an adverse event (AE) which starts after start of first IMP or an AE continues from baseline of the specific corresponding duration and was serious, trial drug-related or results in death, discontinuation, interruption or reduction of IMP. |
Countries
United States
Participant flow
Recruitment details
Participants took part in the study at 2 investigative centers in the United States from 15 September 2021 to 31 May 2022.
Pre-assignment details
A total of 287 participants were screened of which 50 participants were enrolled and treated in this study.
Participants by arm
| Arm | Count |
|---|---|
| Centanafadine Participants received centanafadine SR tablets, orally, at a TDD of 400 mg, administered as 200 mg doses, BID, approximately 4 to 6 hours apart, for a total of 7 weeks. | 50 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Non-Compliance With Study Drug | 5 |
| Overall Study | Physician Decision | 2 |
| Overall Study | Withdrawal by Subject | 6 |
Baseline characteristics
| Characteristic | Centanafadine |
|---|---|
| Age, Continuous | 45.1 years STANDARD_DEVIATION 10.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 48 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants |
| Race/Ethnicity, Customized Multiple | 2 Participants |
| Race/Ethnicity, Customized Other | 1 Participants |
| Race/Ethnicity, Customized White | 31 Participants |
| Sex: Female, Male Female | 24 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 50 |
| other Total, other adverse events | 35 / 50 |
| serious Total, serious adverse events | 1 / 50 |
Outcome results
Primary
Percentage of Participants With a Continuous Smoking Abstinence Rate
Participants were considered abstinent from combustible cigarettes if the participant self-reported tobacco abstinence (no cigarette smoking, not even a puff) assessed by responses to daily messages throughout Weeks 4-7. Any participants lost to follow-up after receiving the investigational product, or who have smoked during Weeks 4-7 were counted as non-abstinent. The binomial confidence interval was based on normal approximation. If the number of abstinent or the number of non-abstinent ≤ 5, exact method was used.
Time frame: Weeks 4 to 7
Population: Full Analysis Set included all participants who were administered at least one dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Centanafadine | Percentage of Participants With a Continuous Smoking Abstinence Rate | 0 percentage of participants |
Primary
Percentage of Participants With Continuous Smoking Abstinence Rate Determined Based on Expired Air Carbon Monoxide (CO) Reading Assessed Using the Vitalograph Breath CO Monitor
Participants were considered abstinent from combustible cigarettes if the participants had an exhaled CO level of less than 5 parts per million (ppm) measured using the Vitalograph Breath CO monitor. Participants with actual data that they were smoking (CO value ≥ 5 ppm or any smoking record in self-report) were counted as non-abstinent The binomial confidence interval was based on normal approximation. If the number of abstinent or the number of non-abstinent ≤ 5, exact method was used.
Time frame: Weeks 4 to 7
Population: Full Analysis Set included all participants who were administered at least one dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Centanafadine | Percentage of Participants With Continuous Smoking Abstinence Rate Determined Based on Expired Air Carbon Monoxide (CO) Reading Assessed Using the Vitalograph Breath CO Monitor | 2.0 percentage of participants |
Secondary
Percentage of Participants With Nausea
Nausea was only considered when it was a treatment-emergent adverse event (TEAE). A TEAE is defined as an adverse event (AE) which starts after start of first IMP or an AE continues from baseline of the specific corresponding duration and was serious, trial drug-related or results in death, discontinuation, interruption or reduction of IMP.
Time frame: From first dose of study drug to 7 days after receiving last dose (Up to Week 8)
Population: Safety Analysis Set included all participants who were administered at least one dose of IMP, regardless of any protocol violation.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Centanafadine | Percentage of Participants With Nausea | 12.0 percentage of participants |