Safety Study of Cytisinicline in Adult Combustible and/or E-cigarette Smokers

NCT06435221 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: ACH-CYT-13
• Study Type: interventional
• Target: 479
• Locations: 1 country
• Sites: 29

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.

Conditions

Smoking Cessation; Vaping Cessation

Outcome Measures

Primary Outcomes (1)

• Incidence Rate of Treatment Emergent Serious Adverse Events (SAEs)

  up to Week 52

Secondary Outcomes (7)

• Incidence Rate of Related Treatment Emergent SAEs

  up to Week 52

• Incidence Rate of Treatment Emergent Adverse Events (TEAEs)

  up to Week 52

• Incidence Rate of Related TEAEs

  up to Week 52

• Number of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters

  up to Week 52

• Percentage of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters

  up to Week 52

Study Arms (1)

Cytisinicline 3 mg TID

EXPERIMENTAL

Cytisinicline 3 mg TID for 52 weeks.

Drug: Cytisinicline

Interventions

Cytisinicline DRUG

film-coated oral tablets containing 3 mg cytisinicline

Also known as: Cytisine

Cytisinicline 3 mg TID

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Prior participation in the ORCA-2, ORCA-3 or ORCA-V1 clinical studies.
• 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.
• 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.
• Willing to initiate cytisinicline treatment on the day after enrollment and set a quit date within 14 days of starting treatment.
• Willing to actively participate in the study's 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.

You may not qualify if:

• Known hypersensitivity to cytisinicline or any of the excipients.
• Clinically significant abnormal screening serum chemistry or hematology values.
• Clinically significant abnormal screening 12-lead ECG determined after minimum of 5 minutes in supine position (ie, requiring treatment or further assessment).
• Recent history (within 3 months prior to screening) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.
• Current uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg).
• 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.
• Severe renal impairment defined as a creatinine clearance (CrCl) \<60 mL/min on screening lab (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) on screening lab.
• Women who are pregnant or breast-feeding.
• 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

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (29)

Alliance for Multispecialty Research, LLC

Mobile, Alabama, 36608, United States

Location

Alliance for Multispecialty Research, LLC

Tempe, Arizona, 85281, United States

Location

Little Rock Allergy & Asthma Clinical Research Center

Little Rock, Arkansas, 72205, United States

Location

Alliance for Multispecialty Research, LLC

Coral Gables, Florida, 33134, United States

Location

Accel Research Sites Network - DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

Location

Alliance for Multispecialty Research, LLC

Fort Myers, Florida, 33912, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Precision Clinical Research

Sunrise, Florida, 33351, United States

Location

Clinical Research Atlanta

Stockbridge, Georgia, 30281, United States

Location

Alliance for Multispecialty Research, LLC

Oak Brook, Illinois, 60523, United States

Location

MediSphere Medical Research Center, LLC

Evansville, Indiana, 47714, United States

Location

Alliance for Multispecialty Research, LLC

Wichita, Kansas, 67207, United States

Location

Alliance for Multispecialty Research, LLC

Lexington, Kentucky, 40509, United States

Location

Alliance for Multispecialty Research, LLC

New Orleans, Louisiana, 70119, United States

Location

Massachusetts General Hospital - Clinical Genetic Facility

Boston, Massachusetts, 02114, United States

Location

Insight Research Institute

Flint, Michigan, 48507, United States

Location

Alliance for Multispecialty Research, LLC

Kansas City, Missouri, 64114, United States

Location

Alliance for Multispecialty Research, LLC

Las Vegas, Nevada, 89119, United States

Location

Global Medical Institutes LLC; Princeton Medical Institute

Princeton, New Jersey, 08540, United States

Location

Rochester Clinical Research, LLC

Rochester, New York, 14609, United States

Location

Centricity Research Columbus Ohio Multispecialty

Columbus, Ohio, 43213, United States

Location

Alliance for Multispecialty Research, LLC

Norman, Oklahoma, 73069, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Coastal Carolina Research Center

North Charleston, South Carolina, 29405, United States

Location

Alliance for Multispecialty Research, LLC

Knoxville, Tennessee, 37909, United States

Location

Clinical Research Associates, Inc.

Nashville, Tennessee, 37203, United States

Location

Clinical Trials of Texas, LLC

San Antonio, Texas, 78229, United States

Location

Health Research of Hampton Roads, Inc.

Newport News, Virginia, 23606, United States

Location

Alliance for Multispecialty Research, LLC

Norfolk, Virginia, 23502, United States

Location

MeSH Terms

Conditions

Smoking Cessation

Interventions

cytisine

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Study Officials

• Julie Ball

  Achieve Life Sciences, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 24, 2024
• First Posted: May 30, 2024
• Study Start: May 28, 2024
• Primary Completion: September 29, 2025
• Study Completion: October 6, 2025
• Last Updated: November 26, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (29)