Clinical trial NCT06435221: Safety Study of Cytisinicline in Adult Combustible And/or E-cigarette Smokers
Official title: A Multicenter, Open-Label Study Assessing Long-Term Exposure with Cytisinicline 3 Mg TID
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Smoking Cessation
Vaping Cessation
Lead sponsor: Achieve Life Sciences
Sponsor class: INDUSTRY
First posted: 2024-05-30
Enrollment: 650
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Safety assessment of long-term 3 mg cytisinicline three times daily (TID) exposure for 52 weeks is the main purpose of this study, conducted in the United States.


Eligibility criteria: Inclusion Criteria:

1. Prior participation in the ORCA-2, ORCA-3 or ORCA-V1 clinical studies.
2. Former ORCA-2/ORCA-3 and ORCA-V1 subjects who are current daily cigarette smokers and/or daily nicotine-containing electronic cigarette users. Amount of daily combustible and/or nicotine containing electronic cigarette use at baseline is determined by subject self-report.
3. At Screening, subjects must have expired carbon monoxide (CO) ≥10 ppm if self-reporting as smokers or ≥30 ng/mL cotinine using a point-of-care cotinine oral fluid screening device if self-reporting as users of nicotine containing electronic cigarettes.
4. Willing to initiate cytisinicline treatment on the day after enrollment and set a quit date within 14 days of starting treatment.
5. Willing to actively participate in the study's cessation behavioral support provided throughout the study.
6. Able to fully understand study requirements, willing to participate, and comply with dosing schedule.
7. Sign the Informed Consent Form.

Exclusion Criteria:

1. Known hypersensitivity to cytisinicline or any of the excipients.
2. Clinically significant abnormal screening serum chemistry or hematology values.
3. Clinically significant abnormal screening 12-lead ECG determined after minimum of 5 minutes in supine position (ie, requiring treatment or further assessment).
4. Recent history (within 3 months prior to screening) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.
5. Current uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg).
6. Currently psychotic or having had a psychotic event within 3 months prior to screening; currently having suicidal ideation or risk for suicide (corresponding to question 4 or 5 on the screening C-SSRS OR "Yes" to any suicidal behavior question on the screening C-SSRS with clear suicidal intent or previous attempt); or current symptoms of moderate to severe depression (depression score ≥11 on the HADS) at screening. If any subject becomes psychotic during the study, they must be removed from cytisinicline treatment and/or additional study visits.
7. Severe renal impairment defined as a creatinine clearance (CrCl) \<60 mL/min on screening lab (estimated with the Cockroft-Gault equation).
8. Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 x the upper limit of normal (ULN) on screening lab.
9. Women who are pregnant or breast-feeding.
10. Female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study. Acceptable methods of birth control include:

    * True abstinence: When this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\].
    * Barrier methods:

      * diaphragm
      * cervical cap
      * contraceptive sponge
    * Hormonal methods:

      * Oral contraceptives
      * Vaginal ring such as NuvaRing
      * Skin patch such as Xulane
      * Injection such as Depro-Provera
      * Implantable rod such as Nexplanon
11. Participation in a clinical study with an investigational drug in the 4 weeks prior to enrollment.
12. 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: Incidence Rate of Treatment Emergent Serious Adverse Events (SAEs)
timeFrame: up to Week 52
Secondary outcomes:
measure: Incidence Rate of Related Treatment Emergent SAEs
timeFrame: up to Week 52
measure: Incidence Rate of Treatment Emergent Adverse Events (TEAEs)
timeFrame: up to Week 52
measure: Incidence Rate of Related TEAEs
timeFrame: up to Week 52
measure: Number of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters
timeFrame: up to Week 52
measure: Percentage of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters
timeFrame: up to Week 52
measure: Number of Participants With Potentially Clinically Significant Abnormal Vital Signs
timeFrame: up to Week 52
measure: Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs
timeFrame: up to Week 52
Other outcomes:
Locations:
city: Mobile
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Alabama
city: Tempe
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Arizona
city: Little Rock
country: United States
facility: Little Rock Allergy & Asthma Clinical Research Center
state: Arkansas
city: Coral Gables
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Florida
city: DeLand
country: United States
facility: Accel Research Sites Network - 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: Sunrise
country: United States
facility: Precision Clinical Research
state: Florida
city: Stockbridge
country: United States
facility: Clinical Research Atlanta
state: Georgia
city: Oak Brook
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Illinois
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: Alliance for Multispecialty Research, LLC
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 Facility
state: Massachusetts
city: Flint
country: United States
facility: Insight Research Institute
state: Michigan
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: Princeton
country: United States
facility: Global Medical Institutes LLC; Princeton Medical Institute
state: New Jersey
city: Rochester
country: United States
facility: Rochester Clinical Research, LLC
state: New York
city: Columbus
country: United States
facility: Centricity Research Columbus Ohio Multispecialty
state: Ohio
city: Norman
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: North Charleston
country: United States
facility: Coastal Carolina Research Center
state: South Carolina
city: Knoxville
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates, Inc.
state: Tennessee
city: San Antonio
country: United States
facility: Clinical Trials of Texas, LLC
state: Texas
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc.
state: Virginia
city: Norfolk
country: United States
facility: Alliance for Multispecialty Research, LLC
state: Virginia
Study officials:
affiliation: Achieve Life Sciences, Inc.
name: Julie Ball
role: STUDY_DIRECTOR
References: