Smoking CessationPhase 3ORCA-OLNCT06435221
Safety Study of Cytisinicline in Adult Combustible and/or E-cigarette Smokers
A Phase 3 study testing Cytisinicline in people with Smoking Cessation and Vaping Cessation, run by Achieve Life Sciences at 29 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Smoking Cessation, Vaping Cessation
- What is being tested?
- Cytisinicline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 479 participants
- Where
- 29 sitesUnited States
- Study dates
- 28 May 2024to 6 Oct 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 23Show fewer
- 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
- Hormonal methods:
- Oral contraceptives
- Vaginal ring such as NuvaRing
- Skin patch such as Xulane
- Injection such as Depro-Provera
- Implantable rod such as Nexplanon
- Participation in a clinical study with an investigational drug in the 4 weeks prior to enrollment.
- Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.
Trial locations and contacts
29 sites in 1 country.
29 sites in 1 country
United States29 sites
Massachusetts General Hospital - Clinical Genetic Facility
Boston, Massachusetts, 02114
Centricity Research Columbus Ohio Multispecialty
Columbus, Ohio, 43213
Alliance for Multispecialty Research, LLC
Coral Gables, Florida, 33134
Accel Research Sites Network - DeLand Clinical Research Unit
DeLand, Florida, 32720
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635
MediSphere Medical Research Center, LLC
Evansville, Indiana, 47714
Insight Research Institute
Flint, Michigan, 48507
Alliance for Multispecialty Research, LLC
Fort Myers, Florida, 33912
Jacksonville Center for Clinical Research
Jacksonville, Florida, 32216
Alliance for Multispecialty Research, LLC
Kansas City, Missouri, 64114
Alliance for Multispecialty Research, LLC
Knoxville, Tennessee, 37909
Alliance for Multispecialty Research, LLC
Las Vegas, Nevada, 89119
Alliance for Multispecialty Research, LLC
Lexington, Kentucky, 40509
Little Rock Allergy & Asthma Clinical Research Center
Little Rock, Arkansas, 72205
Alliance for Multispecialty Research, LLC
Mobile, Alabama, 36608
Clinical Research Associates, Inc.
Nashville, Tennessee, 37203
Alliance for Multispecialty Research, LLC
New Orleans, Louisiana, 70119
Health Research of Hampton Roads, Inc.
Newport News, Virginia, 23606
Alliance for Multispecialty Research, LLC
Norfolk, Virginia, 23502
Alliance for Multispecialty Research, LLC
Norman, Oklahoma, 73069
Coastal Carolina Research Center
North Charleston, South Carolina, 29405
Alliance for Multispecialty Research, LLC
Oak Brook, Illinois, 60523
Global Medical Institutes LLC; Princeton Medical Institute
Princeton, New Jersey, 08540
Rochester Clinical Research, LLC
Rochester, New York, 14609
Clinical Trials of Texas, LLC
San Antonio, Texas, 78229
Clinical Research Atlanta
Stockbridge, Georgia, 30281
Precision Clinical Research
Sunrise, Florida, 33351
Alliance for Multispecialty Research, LLC
Tempe, Arizona, 85281
Alliance for Multispecialty Research, LLC
Wichita, Kansas, 67207
About this study
Official title: 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.
- Conditions
- Smoking Cessation, Vaping Cessation
- Being tested
- Cytisinicline
- Medical subject headings
- Smoking Cessation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CytisiniclineDrug
Also called Cytisine
film-coated oral tablets containing 3 mg cytisinicline
| Study group | Role | What they receive |
|---|---|---|
| Cytisinicline 3 mg TID | Experimental | Cytisinicline 3 mg TID for 52 weeks. Receives: Drug: Cytisinicline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence Rate of Treatment Emergent Serious Adverse Events (SAEs)
Measured: up to Week 52
Secondary outcomes (7)
Incidence Rate of Related Treatment Emergent SAEs
Measured: up to Week 52
Incidence Rate of Treatment Emergent Adverse Events (TEAEs)
Measured: up to Week 52
Incidence Rate of Related TEAEs
Measured: up to Week 52
Number of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters
Measured: up to Week 52
Percentage of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters
Measured: up to Week 52
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs
Measured: up to Week 52
Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs
Measured: up to Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 May 2024
- Study start28 May 2024
- Primary completion29 Sep 2025
- Study completion6 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Smoking CessationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 479 participants (actual)
Sponsor and investigators
- Lead sponsor
- Achieve Life Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Julie Ball, Study director, Achieve Life Sciences, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06435221
- Sponsor's protocol ID
- ACH-CYT-13
- Acronym
- ORCA-OL
- Status last verified
- Nov 2025
- First submitted
- 24 May 2024
- Last updated
- 26 Nov 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Open-Label Study Assessing Long-Term Exposure With Cytisinicline 3 mg TID
- ClinicalTrials.gov ID
- NCT06435221
- Acronym / sponsor ID
- ORCA-OL / ACH-CYT-13
- Conditions
- Smoking Cessation, Vaping Cessation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 479 participants (actual)
- Lead sponsor
- Achieve Life SciencesIndustry (pharma, biotech, devices)
- Study start
- 28 May 2024 (actual)
- Primary completion
- 29 Sep 2025 (actual)
- Study completion
- 6 Oct 2025 (actual)
- First posted
- 30 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cytisinicline 3 mg TID | Experimental | Drug: CytisiniclineCytisinicline 3 mg TID for 52 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (23 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CytisiniclineAlso: Cytisinefilm-coated oral tablets containing 3 mg cytisinicline | Drug | Cytisinicline 3 mg TID |
Primary outcome
Incidence Rate of Treatment Emergent Serious Adverse Events (SAEs)
Time frame: up to Week 52
7 secondary outcomes
Incidence Rate of Related Treatment Emergent SAEs
Time frame: up to Week 52
Incidence Rate of Treatment Emergent Adverse Events (TEAEs)
Time frame: up to Week 52
Incidence Rate of Related TEAEs
Time frame: up to Week 52
Number of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters
Time frame: up to Week 52
Percentage of Participants With Clinically Significant Abnormal Hematology and Chemistry Parameters
Time frame: up to Week 52
Number of Participants With Potentially Clinically Significant Abnormal Vital Signs
Time frame: up to Week 52
Percentage of Participants With Potentially Clinically Significant Abnormal Vital Signs
Time frame: up to Week 52
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2025.
- Individual participant dataSharing planned: No
Related trials for Smoking Cessation
Enrolling by invitationObservational study
Using Smartwatches to Monitor Smoking in Real-life Situations
Smoking
Not yet recruitingObservational study
PROMETHEE: A Shared Interregional Tele-Tobacco Cessation Platform Embedded Within the IMPULSION Lung Cancer Screening Program
Smoking Cessation, Lung Cancer Screening
Not yet recruiting
Impacto 2.0: Mobile Smoking Cessation Across Texas
Cigarette Smoking, Smoking Cessation
Not yet recruiting
Smoking Cessation Program for Lao People With HIV
Smoking Cessation, HIV
RecruitingPhase 3
Studying NMDA and Sigma-1 in Smoking Cessation Treatment (SUMMIT)
Smoking Cessation
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julie Ball study director
Achieve Life Sciences, Inc.
29 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cytisinicline in people with Smoking Cessation and Vaping Cessation, run by Achieve Life Sciences at 29 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence Rate of Treatment Emergent Serious Adverse Events (SAEs) (time frame: up to Week 52). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2025.