Safety Study of Cytisinicline in Adult Combustible and/or E-cigarette Smokers (ORCA-OL)

A Multicenter, Open-Label Study Assessing Long-Term Exposure With Cytisinicline 3 mg TID

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.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Vaping Cessation
• Intervention / Treatment: Drug: Cytisinicline

• Study Type: Interventional
• Enrollment (Actual): 479
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Alliance For multispecialty Research, LLC
  • Arizona
    • Tempe, Arizona, United States, 85281
      • Alliance For multispecialty Research, LLC
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Little Rock Allergy & Asthma Clinical Research Center
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Alliance For multispecialty Research, LLC
    • DeLand, Florida, United States, 32720
      • Accel Research Sites Network - DeLand Clinical Research Unit
    • Fort Myers, Florida, United States, 33912
      • Alliance For multispecialty Research, LLC
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center for Clinical Research
    • Sunrise, Florida, United States, 33351
      • Precision Clinical Research
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Clinical Research Atlanta
  • Illinois
    • Oak Brook, Illinois, United States, 60523
      • Alliance For multispecialty Research, LLC
  • Indiana
    • Evansville, Indiana, United States, 47714
      • MediSphere Medical Research Center, LLC
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Alliance For multispecialty Research, LLC
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Alliance For multispecialty Research, LLC
  • Louisiana
    • New Orleans, Louisiana, United States, 70119
      • Alliance For multispecialty Research, LLC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital - Clinical Genetic Facility
  • Michigan
    • Flint, Michigan, United States, 48507
      • Insight Research Institute
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • Alliance For multispecialty Research, LLC
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Alliance For multispecialty Research, LLC
  • New Jersey
    • Princeton, New Jersey, United States, 08540
      • Global Medical Institutes LLC; Princeton Medical Institute
  • New York
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, LLC
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Centricity Research Columbus Ohio Multispecialty
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • Alliance For multispecialty Research, LLC
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research
  • South Carolina
    • North Charleston, South Carolina, United States, 29405
      • Coastal Carolina Research Center
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Alliance For multispecialty Research, LLC
    • Nashville, Tennessee, United States, 37203
      • Clinical Research Associates, Inc.
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.
    • Norfolk, Virginia, United States, 23502
      • Alliance For multispecialty Research, LLC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cytisinicline 3 mg TID; Cytisinicline 3 mg TID for 52 weeks.	Drug: Cytisinicline; film-coated oral tablets containing 3 mg cytisinicline; Other Names: Cytisine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence Rate of Treatment Emergent Serious Adverse Events (SAEs)	up to Week 52

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs	up to Week 52
Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs	up to Week 52

Collaborators and Investigators

• Sponsor: Achieve Life Sciences
• Investigators: Study Director: Julie Ball, Achieve Life Sciences, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2024
• Primary Completion (Actual): September 29, 2025
• Study Completion (Actual): October 6, 2025

Study Registration Dates

• First Submitted: May 24, 2024
• First Submitted That Met QC Criteria: May 24, 2024
• First Posted (Actual): May 30, 2024

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Health Behavior; Smoking Cessation; cytisine
• Other Study ID Numbers: ACH-CYT-13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No