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

November 21, 2025 updated by: Achieve Life Sciences

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
479

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Incidence Rate of Treatment Emergent Serious Adverse Events (SAEs)
Time Frame: up to Week 52
up to Week 52

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Incidence Rate of Related Treatment Emergent SAEs
Time Frame: up to Week 52
up to Week 52
Incidence Rate of Treatment Emergent Adverse Events (TEAEs)
Time Frame: up to Week 52
up to Week 52
Incidence Rate of Related TEAEs
Time Frame: up to Week 52
up to Week 52
Number of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters
Time Frame: up to Week 52
up to Week 52
Percentage of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters
Time Frame: up to Week 52
up to Week 52
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs
Time Frame: up to Week 52
up to Week 52
Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs
Time Frame: up to Week 52
up to Week 52

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Achieve Life Sciences

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Julie Ball, Achieve Life Sciences, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 28, 2024

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 29, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 6, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 24, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 24, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 30, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 26, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 21, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings