Smoking Cessation
Conditions
Brief summary
This placebo-controlled Phase 3 study is being conducted at sites within the United States to evaluate 3 mg cytisinicline TID for treatment duration of 42 days/6 weeks and evaluate 3 mg cytisinicline TID for treatment duration of 84 days/12 weeks.
Interventions
DRUGCytisinicline
film-coated oral tablets containing 3 mg cytisinicline
DRUGPlacebo
film-coated oral tablets containing matched placebo
BEHAVIORALBehavioral support
Behavioral support sessions by a qualified study site staff member will be participant-driven and will include direct engagement with the subject about their attempt to quit smoking. Each session will last approximately 10 minutes.
Sponsors
Achieve Life Sciences
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects, age ≥ 18 years. 2. Current daily cigarette smokers (averaging at least 10 cigarettes per day upon completing a 7-day screening smoking diary) and who intend to quit smoking. 3. Expired air carbon monoxide (CO) ≥ 10 ppm. 4. Failed at least one previous attempt to stop smoking with or without therapeutic support. 5. Willing to initiate study treatment on the day after randomization and set a quit date within 5-7 days of starting treatment. 6. Willing to actively participate in the study's smoking cessation behavioral support provided throughout the study. 7. Able to fully understand all study requirements, willing to participate, and comply with dosing schedule. 8. Sign the Informed Consent Form.
Exclusion criteria
1. More than 1 study participant in same household during the 12-week treatment period. 2. Previous cytisinicline treatment in a prior clinical study or any other cytisine usage. 3. Known hypersensitivity to cytisinicline or any of the excipients. 4. Positive urinary drugs of abuse screen, determined within 28 days before the first dose of cytisinicline. 5. Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (ie, requiring treatment or monitoring). 6. Clinically significant abnormalities in 12-lead ECG determined after minimum of 5 minutes in supine position within 28 days of randomization (ie, requiring treatment or further assessment). 7. Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident, or hospitalization for congestive heart failure. 8. Current uncontrolled hypertension (blood pressure ≥160/100 mmHg). 9. Currently psychotic or having had a psychotic event within 3 months. If any subject becomes psychotic during the study, they must be removed from treatment and/or additional study visits. 10. Currently having suicidal ideation or risk for suicide (Yes to either question 4 or question 5 OR Yes to any suicidal behavior question on the Columbia Suicide Severity Rating Scale \[C-SSRS\] with clear suicidal intent or previous attempt). 11. Current symptoms of moderate to severe depression (depression score ≥11on the HADS). 12. Renal impairment defined as a creatinine clearance (CrCl) \<60 mL/min (estimated with the Cockroft-Gault equation). 13. Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 x the upper limit of normal (ULN). 14. Women who are pregnant or breast-feeding. 15. Male or female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study treatment period. 16. Participation in a clinical study with an investigational drug in the 4 weeks prior to randomization. 17. Treatment with other smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy \[NRT\]) in the 4 weeks prior to randomization or planned use of these other smoking cessation medications during the study. 18. Use within the 2 weeks prior to randomization or planned use during the study of non-cigarette and/or noncombustible nicotine products (pipe tobacco, cigars, snuff, smokeless tobacco, hookah, e-cigarettes/vaping) or marijuana smoking or vaping. 19. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6 | Weeks 3 to 6 | Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements ≤ 10 parts per million (ppm). |
| Percentage of Participants With Smoking Abstinence From Weeks 9 to Week 12 | Weeks 9 to 12 | Smoking abstinence as verified by weekly expired CO measurements ≤ 10 ppm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Continuous Smoking Abstinence From Week 3 to Week 24 | Week 3 to Week 24 | Smoking abstinence as verified by expired CO measurements ≤ 10 ppm. Measurements were weekly from Week 3 to Week 12 and monthly from Week 12 to Week 24. |
| Percentage of Participants With Continuous Smoking Abstinence From Week 9 to Week 24 | Week 9 to Week 24 | Smoking abstinence as verified by expired CO measurements ≤ 10 ppm. Measurements were weekly from Week 9 to Week 12 and monthly from Week 12 to Week 24. |
| Percentage of Participants Taking Cytisinicline Who Are Relapse-Free at Week 24 | Week 24 | Relapse is defined as participant reported resuming smoking or an expired CO measure ≥ 10 ppm. Relapse is defined as a participant having met one of the following: not being abstinent from Weeks 3 to 6; not being abstinent at the Week 12 visit; not being abstinent or not self-reporting abstinence during the Week 16 to Week 24 follow-up period. (During the follow-up period \[Weeks 16 to 24\], up to a total of 5 cigarettes could have been smoked.) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo + Behavioral Support One placebo tablet PO TID for 12 weeks plus behavioral support | 265 |
| 6-Week Cytisinicline + 6-Week Placebo + Behavioral Support One cytisinicline tablet PO TID for 6 weeks followed by one placebo tablet PO TID for 6 weeks plus behavioral support | 263 |
| 12-Week Cytisinicline + Behavioral Support One cytisinicline tablet PO TID for 12 weeks plus behavioral support | 264 |
| Total | 792 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 | 5 |
| Overall Study | Death | 0 | 1 | 3 |
| Overall Study | Lost to Follow-up | 23 | 16 | 14 |
| Overall Study | Other, Nor Specified | 2 | 2 | 4 |
| Overall Study | Physician Decision | 1 | 3 | 2 |
| Overall Study | Withdrawal by Subject | 27 | 30 | 24 |
Baseline characteristics
| Characteristic | Placebo + Behavioral Support | 6-Week Cytisinicline + 6-Week Placebo + Behavioral Support | 12-Week Cytisinicline + Behavioral Support | Total |
|---|---|---|---|---|
| Age, Continuous | 51 years STANDARD_DEVIATION 11.4 | 52 years STANDARD_DEVIATION 11.7 | 52 years STANDARD_DEVIATION 12.3 | 52 years STANDARD_DEVIATION 11.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants | 15 Participants | 13 Participants | 45 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 248 Participants | 248 Participants | 251 Participants | 747 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 4 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 2 Participants | 2 Participants | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 51 Participants | 38 Participants | 50 Participants | 139 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 3 Participants | 3 Participants | 5 Participants | 11 Participants |
| Race/Ethnicity, Customized White | 210 Participants | 216 Participants | 205 Participants | 631 Participants |
| Sex: Female, Male Female | 146 Participants | 142 Participants | 151 Participants | 439 Participants |
| Sex: Female, Male Male | 119 Participants | 121 Participants | 113 Participants | 353 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 262 | 1 / 263 | 3 / 260 |
| other Total, other adverse events | 110 / 262 | 132 / 263 | 137 / 260 |
| serious Total, serious adverse events | 8 / 262 | 8 / 263 | 8 / 260 |
Outcome results
Primary
Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6
Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements ≤ 10 parts per million (ppm).
Time frame: Weeks 3 to 6
Population: All Randomized Set: all randomized participants. Placebo and 6-week treatment arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Behavioral Support | Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6 | 6.0 percentage of participants |
| 6-Week Cytisinicline + 6-Week Placebo + Behavioral Support | Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6 | 14.8 percentage of participants |
p-value: 0.000895% CI: [1.475, 5.617]Exact computations
p-value: 0.00195% CI: [1.485, 5.094]Exact computations
p-value: 0.000695% CI: [0.033, 0.134]Cochran-Mantel-Haenszel
Primary
Percentage of Participants With Smoking Abstinence From Weeks 9 to Week 12
Smoking abstinence as verified by weekly expired CO measurements ≤ 10 ppm.
Time frame: Weeks 9 to 12
Population: All Randomized Set: all randomized participants, Placebo and 12-week treatment arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Behavioral Support | Percentage of Participants With Smoking Abstinence From Weeks 9 to Week 12 | 9.4 percentage of participants |
| 6-Week Cytisinicline + 6-Week Placebo + Behavioral Support | Percentage of Participants With Smoking Abstinence From Weeks 9 to Week 12 | 30.3 percentage of participants |
Comparison: Abstinence from Week 9 to Week 12p-value: <0.000195% CI: [2.566, 7.343]Exact computations
p-value: <0.000195% CI: [2.575, 6.885]Exact computations
p-value: <0.000195% CI: [0.141, 0.267]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Taking Cytisinicline Who Are Relapse-Free at Week 24
Relapse is defined as participant reported resuming smoking or an expired CO measure ≥ 10 ppm. Relapse is defined as a participant having met one of the following: not being abstinent from Weeks 3 to 6; not being abstinent at the Week 12 visit; not being abstinent or not self-reporting abstinence during the Week 16 to Week 24 follow-up period. (During the follow-up period \[Weeks 16 to 24\], up to a total of 5 cigarettes could have been smoked.)
Time frame: Week 24
Population: All Randomized Set: All randomized participants. Participants in the cytisinicline arms.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Behavioral Support | Percentage of Participants Taking Cytisinicline Who Are Relapse-Free at Week 24 | 8.7 percentage of participants |
| 6-Week Cytisinicline + 6-Week Placebo + Behavioral Support | Percentage of Participants Taking Cytisinicline Who Are Relapse-Free at Week 24 | 10.6 percentage of participants |
Comparison: Relapse free at Week 24p-value: 0.553895% CI: [0.652, 2.297]Exact computations
p-value: 0.55695% CI: [0.691, 2.231]Exact computations
p-value: 0.2822Zelen's exact test (Pr ≤ P)
Secondary
Percentage of Participants With Continuous Smoking Abstinence From Week 3 to Week 24
Smoking abstinence as verified by expired CO measurements ≤ 10 ppm. Measurements were weekly from Week 3 to Week 12 and monthly from Week 12 to Week 24.
Time frame: Week 3 to Week 24
Population: All Randomized Set: all randomized participants, Placebo and 6-week treatment arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Behavioral Support | Percentage of Participants With Continuous Smoking Abstinence From Week 3 to Week 24 | 1.1 percentage of participants |
| 6-Week Cytisinicline + 6-Week Placebo + Behavioral Support | Percentage of Participants With Continuous Smoking Abstinence From Week 3 to Week 24 | 6.8 percentage of participants |
Comparison: Abstinence from Week 6 to Week 24p-value: 0.000695% CI: [1.851, 34.619]Exact computations
p-value: 0.000795% CI: [2.026, 27.544]Exact computations
p-value: 0.000795% CI: [0.023, 0.075]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Continuous Smoking Abstinence From Week 9 to Week 24
Smoking abstinence as verified by expired CO measurements ≤ 10 ppm. Measurements were weekly from Week 9 to Week 12 and monthly from Week 12 to Week 24.
Time frame: Week 9 to Week 24
Population: All Randomized Set: all randomized participants, Placebo and 12-week treatment arms only.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + Behavioral Support | Percentage of Participants With Continuous Smoking Abstinence From Week 9 to Week 24 | 4.2 percentage of participants |
| 6-Week Cytisinicline + 6-Week Placebo + Behavioral Support | Percentage of Participants With Continuous Smoking Abstinence From Week 9 to Week 24 | 20.5 percentage of participants |
Comparison: Abstinence from Week 9 to Week 24p-value: <0.000195% CI: [2.888, 12.458]Exact computations
p-value: <0.000195% CI: [3.091, 12.13]Exact computations
p-value: <0.000195% CI: [0.11, 0.202]Cochran-Mantel-Haenszel