A Study of Cytisinicline for Smoking Cessation in Adult Smokers

Phase 3

Completed

• Conditions: Smoking Cessation
• Interventions: Drug: Placebo; Drug: Cytisinicline; Behavioral: Behavioral support

• Registration Number: NCT04576949
• Lead Sponsor: Achieve Life Sciences

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-25
• Study First Submitted QC: 2020-09-30
• Study First Posted: 2020-10-06
• Study Start: 2020-10-13
• Primary Completion: 2021-12-23
• Study Completion: 2021-12-23
• Disposition First Submitted: 2022-12-01
• Disposition First Submitted QC: 2022-12-01
• Disposition First Posted: 2022-12-06
• Status Verified: 2024-10
• Results First Submitted: 2024-10-22
• Results First Submitted QC: 2024-10-22
• Last Update Submitted: 2024-10-22
• Results First Posted: 2024-11-14
• Last Update Posted: 2024-11-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 810

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 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.
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 electrocardiogram (ECG) determined after minimum of 5 minutes in supine position within 28 days of randomization (ie, requiring treatment or further assessment).
7. Body mass index (BMI) classification for being underweight (<18.5 kg/m^2) or having ≥Class 2 obesity (≥35 kg/m^2).
8. Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.
9. Current uncontrolled hypertension (blood pressure ≥160/100 mmHg).
10. Documented diagnosis of schizophrenia or bipolar psychiatric illness; currently psychotic.
11. 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]).
12. Current symptoms of moderate to severe depression (Hospital Anxiety and Depression Scale[HADS] score ≥11).
13. Renal impairment defined as a creatinine clearance (CrCl) <60 mL/min (estimated with the Cockroft-Gault equation).
14. Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2.0 x the upper limit of normal (ULN).
15. Women who are pregnant or breast-feeding.
16. Male or female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study treatment period.
17. Participation in a clinical study with an investigational drug in the 4 weeks prior to randomization.
18. 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.
19. 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.
20. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cytisinicline + Placebo + Behavioral Support	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
Cytisinicline + Behavioral Support	Behavioral support	one cytisinicline tablet PO TID plus behavioral support for 12 weeks
Placebo + Behavioral Support	Placebo	one placebo tablet orally (PO) three times daily (TID) plus behavioral support for 12 weeks
Placebo + Behavioral Support	Behavioral support	one placebo tablet orally (PO) three times daily (TID) plus behavioral support for 12 weeks
Cytisinicline + Placebo + Behavioral Support	Placebo	one cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks
Cytisinicline + Behavioral Support	Cytisinicline	one cytisinicline tablet PO TID plus behavioral support for 12 weeks
Cytisinicline + Placebo + Behavioral Support	Cytisinicline	one cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Percentage of Participants With Continuous Smoking Abstinence From Week 6 to Week 24	Week 6 to Week 24	Smoking abstinence as verified by expired CO measurements ≤10 ppm. Measurements were weekly from Week 6 to Week 12 and monthly from Week 12 to Week 16.
Percentage of Participants With Continuous Smoking Abstinence From Week 12 to Week 24	Week 12 to Week 24	Smoking abstinence as verified by expired CO measurements ≤10 ppm. Measurements were monthly from Week 12 to Week 24.
Percentage of Participants Taking Cytisinicline Who Were Relapse-Free at Week 24	Week 24	Relapse is defined as participant reported resuming smoking or an expired CO measure ≥ 10ppm. 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 abstinent or not self-reported abstinent during the Week 16 to Week 24 follow-up period. (During the follow-up period (Weeks 16 - 24) up to a total of 5 cigarettes could have been smoked.)

Trial Locations

Locations (11)

Arizona State University; 🇺🇸 Phoenix, Arizona, United States

FutureSearch Trials of Dallas, LP; 🇺🇸 Dallas, Texas, United States

Alliance for Multispecialty Research, LLC.; 🇺🇸 Knoxville, Tennessee, United States

AMR Lexington; 🇺🇸 Lexington, Kentucky, United States

Coastal Carolina Research Center, Inc.; 🇺🇸 Mount Pleasant, South Carolina, United States

Massachusetts General Hospital - Clinical Genetic Research Facility; 🇺🇸 Boston, Massachusetts, United States

Rochester Clinical Research, Inc.; 🇺🇸 Rochester, New York, United States

M3 Wake Research, Inc.; 🇺🇸 Raleigh, North Carolina, United States

Clinical Research Atlanta; 🇺🇸 Atlanta, Georgia, United States

MediSphere Medical Research Center, LLC; 🇺🇸 Evansville, Indiana, United States

Alliance for Multispecialty Research, LLC; 🇺🇸 Norfolk, Virginia, United States