Clinical trial NCT05206370: A Second Study of Cytisinicline for Smoking Cessation in Adult Smokers
Official title: A Second 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: 2022-01-25
Enrollment: 792
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 TID for treatment duration of 42 days/6 weeks as well as repeating that duration for a total of 84 days/12 weeks treatment.


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 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 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.

Primary outcomes:
measure: Proportion of Participants With Smoking Abstinence During the Last 4 Weeks of 6 Weeks Cytisinicline Treatment Versus Placebo Treatment (Wk 3-6)
timeFrame: Week 3-6
measure: Proportion of Participants With Smoking Abstinence During the Last 4 Weeks of 12 Weeks Cytisinicline Treatment Versus Placebo Treatment (Wk 9-12)
timeFrame: Week 9-12
Secondary outcomes:
measure: Proportion of Participants With Continuous Smoking Abstinence to Week 24
timeFrame: Week 24
measure: Proportion of Participants Who are Relapse-Free at Week 24
timeFrame: Week 24
Other outcomes:
Locations:
city: DeLand
country: United States
facility: Accel Research Sites - DeLand Clinical Research Unit
state: Florida
city: Fort Myers
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research
state: Florida
city: Oak Brook
country: United States
facility: Affinity Health Corp
state: Illinois
city: Evansville
country: United States
facility: MediSphere Medical Research Center, LLC
state: Indiana
city: Princeton
country: United States
facility: Global Medical Institutes LLC; Princeton Medical Institute
state: New Jersey
city: Wilmington
country: United States
facility: Trial Management Associates, LLC
state: North Carolina
city: Cleveland
country: United States
facility: Velocity Clinical Research, Inc.
state: Ohio
city: Columbus
country: United States
facility: Aventiv Research Inc
state: Ohio
city: Norman
country: United States
facility: Intend Research
state: Oklahoma
city: Nashville
country: United States
facility: Clinical Research Associates, Inc.
state: Tennessee
city: Newport News
country: United States
facility: Health Research of Hampton Toads, Inc
state: Virginia
Study officials:
affiliation: Achieve Life Sciences, Inc.
name: Daniel Cain, Vice-President Clinical Research
role: STUDY_DIRECTOR
References: