A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline in Adult Smokers
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- Achieve Life Sciences
- Enrollment
- 810
- Locations
- 17
- Primary Endpoint
- Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6
Study Overview
Brief Summary
This placebo-controlled Phase 3 study is being conducted at sites within the United States to evaluate 3 mg cytisinicline 3 times daily (TID) for treatment duration of 42 days/6 weeks and evaluate 3 mg cytisinicline TID for treatment duration of 84 days/12 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male or female subjects, age ≥18 years.
- •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.
- •Expired air carbon monoxide (CO) ≥10 ppm.
- •Failed at least one previous attempt to stop smoking with or without therapeutic support.
- •Willing to initiate study treatment on the day after randomization and set a quit date within 5-7 days of starting treatment.
- •Willing to actively participate in the study's smoking cessation behavioral support provided throughout the study.
- •Able to fully understand study requirements, willing to participate, and comply with dosing schedule.
- •Sign the Informed Consent Form.
Exclusion Criteria
- •More than 1 study participant in same household.
- •Previous cytisinicline treatment in a prior clinical study or any other cytisine usage.
- •Known hypersensitivity to cytisinicline or any of the excipients.
- •Positive urinary drugs of abuse screen, determined within 28 days before the first dose of cytisinicline.
- •Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (ie, requiring treatment or monitoring).
- •Clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined after minimum of 5 minutes in supine position within 28 days of randomization (ie, requiring treatment or further assessment).
- •Body mass index (BMI) classification for being underweight (<18.5 kg/m^2) or having ≥Class 2 obesity (≥35 kg/m^2).
- •Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.
- •Current uncontrolled hypertension (blood pressure ≥160/100 mmHg).
- •Documented diagnosis of schizophrenia or bipolar psychiatric illness; currently psychotic.
- •Currently having suicidal ideation or risk for suicide ("Yes" to question 4 or question 5 OR "Yes" to any suicidal behavior question on the Columbia - Suicide Severity Rating Scale [C-SSRS]).
- •Current symptoms of moderate to severe depression (Hospital Anxiety and Depression Scale[HADS] score ≥11).
- •Renal impairment defined as a creatinine clearance (CrCl) <60 mL/min (estimated with the Cockroft-Gault equation).
- •Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 x the upper limit of normal (ULN).
- •Women who are pregnant or breast-feeding.
- •Male or female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study treatment period.
- •Participation in a clinical study with an investigational drug in the 4 weeks prior to randomization.
- •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.
- •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.
- •Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.
Arms & Interventions
Placebo + Behavioral Support
one placebo tablet orally (PO) three times daily (TID) plus behavioral support for 12 weeks
Intervention: Placebo (Drug)
Placebo + Behavioral Support
one placebo tablet orally (PO) three times daily (TID) plus behavioral support for 12 weeks
Intervention: Behavioral support (Behavioral)
Cytisinicline + Placebo + Behavioral Support
one cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks
Intervention: Cytisinicline (Drug)
Cytisinicline + Placebo + Behavioral Support
one cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks
Intervention: Placebo (Drug)
Cytisinicline + Placebo + Behavioral Support
one cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks
Intervention: Behavioral support (Behavioral)
Cytisinicline + Behavioral Support
one cytisinicline tablet PO TID plus behavioral support for 12 weeks
Intervention: Cytisinicline (Drug)
Cytisinicline + Behavioral Support
one cytisinicline tablet PO TID plus behavioral support for 12 weeks
Intervention: Behavioral support (Behavioral)
Outcomes
Primary Outcomes
Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6
Time Frame: 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
Time Frame: Weeks 9 to 12
Smoking abstinence as verified by weekly expired CO measurements ≤10 ppm.
Secondary Outcomes
- Percentage of Participants With Continuous Smoking Abstinence From Week 6 to Week 24(Week 6 to Week 24)
- Percentage of Participants With Continuous Smoking Abstinence From Week 12 to Week 24(Week 12 to Week 24)
- Percentage of Participants Taking Cytisinicline Who Were Relapse-Free at Week 24(Week 24)