Clinical trial NCT04576949: A Study of Cytisinicline for Smoking Cessation in Adult Smokers
Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline in Adult Smokers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Smoking Cessation
Lead sponsor: Achieve Life Sciences
Sponsor class: INDUSTRY
First posted: 2020-10-06
Enrollment: 810
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6
timeFrame: Weeks 3 to 6
measure: Percentage of Participants With Smoking Abstinence From Weeks 9 to Week 12
timeFrame: Weeks 9 to 12
Secondary outcomes:
measure: Percentage of Participants With Continuous Smoking Abstinence From Week 6 to Week 24
timeFrame: Week 6 to Week 24
measure: Percentage of Participants With Continuous Smoking Abstinence From Week 12 to Week 24
timeFrame: Week 12 to Week 24
measure: Percentage of Participants Taking Cytisinicline Who Were Relapse-Free at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Alliance for Multispecialty Research, LLC.
state: Alabama
city: Phoenix
country: United States
facility: Arizona State University
state: Arizona
city: Coral Gables
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Florida
city: Atlanta
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC
state: Indiana
city: Wichita
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Kansas
city: Lexington
country: United States
facility: AMR Lexington
state: Kentucky
city: New Orleans
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital - Clinical Genetic Research Facility
state: Massachusetts
city: Kansas City
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Missouri
city: Las Vegas
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Nevada
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc.
state: New York
city: Raleigh
country: United States
facility: M3 Wake Research, Inc.
state: North Carolina
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center, Inc.
state: South Carolina
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC.
state: Tennessee
city: Dallas
country: United States
facility: FutureSearch Trials of Dallas, LP
state: Texas
city: Norfolk
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Virginia
Study officials:
affiliation: Mass General/Harvard Medical School
name: Nancy Rigotti, MD
role: PRINCIPAL_INVESTIGATOR
References: