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Smoking CessationPhase 3ORCA-2NCT04576949

A Study of Cytisinicline for Smoking Cessation in Adult Smokers

A Phase 3 study testing Cytisinicline and Behavioral support in people with Smoking Cessation, run by Achieve Life Sciences at 17 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This placebo-controlled Phase 3 study is being conducted at sites within the United States to evaluate 3 mg cytisinicline 3 times daily (TID) for treatment duration of 42 days/6 weeks and evaluate 3 mg cytisinicline TID for treatment duration of 84 days/12 weeks. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Smoking Cessation
What is being tested?
Cytisinicline and Behavioral support
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
810 participants
Where
17 sitesUnited States
Study dates
13 Oct 2020to 23 Dec 2021
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Male or female subjects, age ≥18 years.
  • Current daily cigarette smokers (averaging at least 10 cigarettes per day upon completing a 7-day screening smoking diary) and who intend to quit smoking.
  • Expired air carbon monoxide (CO) ≥10 ppm.
  • Failed at least one previous attempt to stop smoking with or without therapeutic support.
  • Willing to initiate study treatment on the day after randomization and set a quit date within 5-7 days of starting treatment.
  • Willing to actively participate in the study's smoking 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

  • More than 1 study participant in same household.
  • Previous cytisinicline treatment in a prior clinical study or any other cytisine usage.
  • Known hypersensitivity to cytisinicline or any of the excipients.
  • Positive urinary drugs of abuse screen, determined within 28 days before the first dose of cytisinicline.
  • Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (ie, requiring treatment or monitoring).
  • Clinically significant abnormalities in 12-lead electrocardiogram (ECG) determined after minimum of 5 minutes in supine position within 28 days of randomization (ie, requiring treatment or further assessment).
Show all 20Show fewer
  • Body mass index (BMI) classification for being underweight (<18.5 kg/m^2) or having ≥Class 2 obesity (≥35 kg/m^2).
  • Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident or hospitalization for congestive heart failure.
  • Current uncontrolled hypertension (blood pressure ≥160/100 mmHg).
  • Documented diagnosis of schizophrenia or bipolar psychiatric illness; currently psychotic.
  • Currently having suicidal ideation or risk for suicide ("Yes" to question 4 or question 5 OR "Yes" to any suicidal behavior question on the Columbia - Suicide Severity Rating Scale [C-SSRS]).
  • Current symptoms of moderate to severe depression (Hospital Anxiety and Depression Scale[HADS] score ≥11).
  • Renal impairment defined as a creatinine clearance (CrCl) <60 mL/min (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).
  • Women who are pregnant or breast-feeding.
  • Male or female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study treatment period.
  • Participation in a clinical study with an investigational drug in the 4 weeks prior to randomization.
  • Treatment with other smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy [NRT]) in the 4 weeks prior to randomization or planned use of these other smoking cessation medications during the study.
  • Use within the 2 weeks prior to randomization or planned use during the study of non-cigarette and/or noncombustible nicotine products (pipe tobacco, cigars, snuff, smokeless tobacco, hookah, e-cigarettes/vaping) or marijuana smoking or vaping.
  • 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

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • Clinical Research Atlanta

    Atlanta, Georgia, 30281

  • Massachusetts General Hospital - Clinical Genetic Research Facility

    Boston, Massachusetts, 02114

  • Alliance for Multispecialty Research, LLC

    Coral Gables, Florida, 33134

  • FutureSearch Trials of Dallas, LP

    Dallas, Texas, 75231

  • MediSphere Medical Research Center, LLC

    Evansville, Indiana, 47714

  • Alliance for Multispecialty Research, LLC

    Kansas City, Missouri, 64114

  • Alliance for Multispecialty Research, LLC.

    Knoxville, Tennessee, 37920

  • Alliance for Multispecialty Research, LLC

    Las Vegas, Nevada, 89119

  • AMR Lexington

    Lexington, Kentucky, 40509

  • Alliance for Multispecialty Research, LLC.

    Mobile, Alabama, 36608

  • Coastal Carolina Research Center, Inc.

    Mt. Pleasant, South Carolina, 29464

  • Alliance for Multispecialty Research, LLC

    New Orleans, Louisiana, 70119

  • Alliance for Multispecialty Research, LLC

    Norfolk, Virginia, 23502

  • Arizona State University

    Phoenix, Arizona, 85044

  • M3 Wake Research, Inc.

    Raleigh, North Carolina, 27612

  • Rochester Clinical Research, Inc.

    Rochester, New York, 14609

  • Alliance for Multispecialty Research, LLC

    Wichita, Kansas, 67207

Other trials in United States

About this study

Official title: A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline in Adult Smokers

This placebo-controlled Phase 3 study is being conducted at sites within the United States to evaluate 3 mg cytisinicline 3 times daily (TID) for treatment duration of 42 days/6 weeks and evaluate 3 mg cytisinicline TID for treatment duration of 84 days/12 weeks.

Being tested
Cytisinicline, Placebo, Behavioral support
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

  • PlaceboDrug

    film-coated oral tablets containing matched placebo

  • Behavioral supportBehavioural

    Behavioral support sessions by a qualified study site staff member will be participant-driven and will include direct engagement with the subject about their attempt to quit smoking. Each session will last approximately 10 minutes.

Study groups in NCT04576949
Study groupRoleWhat they receive
Placebo + Behavioral SupportPlacebo comparatorone placebo tablet orally (PO) three times daily (TID) plus behavioral support for 12 weeks
Receives: Drug: Placebo; Behavioral: Behavioral support
Cytisinicline + Placebo + Behavioral SupportExperimentalone cytisinicline tablet PO TID plus behavioral support for 6 weeks followed by one placebo tablet PO TID plus behavioral support for 6 weeks
Receives: Drug: Cytisinicline; Drug: Placebo; Behavioral: Behavioral support
Cytisinicline + Behavioral SupportExperimentalone cytisinicline tablet PO TID plus behavioral support for 12 weeks
Receives: Drug: Cytisinicline; Behavioral: Behavioral support

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6

    Smoking abstinence as verified by weekly expired carbon monoxide (CO) measurements ≤10 parts per million (ppm).

    Measured: Weeks 3 to 6

  2. Percentage of Participants With Smoking Abstinence From Weeks 9 to Week 12

    Smoking abstinence as verified by weekly expired CO measurements ≤10 ppm.

    Measured: Weeks 9 to 12

Secondary outcomes (3)

  1. Percentage of Participants With Continuous Smoking Abstinence From Week 6 to Week 24

    Smoking abstinence as verified by expired CO measurements ≤10 ppm. Measurements were weekly from Week 6 to Week 12 and monthly from Week 12 to Week 16.

    Measured: Week 6 to Week 24

  2. Percentage of Participants With Continuous Smoking Abstinence From Week 12 to Week 24

    Smoking abstinence as verified by expired CO measurements ≤10 ppm. Measurements were monthly from Week 12 to Week 24.

    Measured: Week 12 to Week 24

  3. Percentage of Participants Taking Cytisinicline Who Were Relapse-Free at Week 24

    Relapse is defined as participant reported resuming smoking or an expired CO measure ≥ 10ppm. Relapse is defined as a participant having met one of the following: not being abstinent from Weeks 3 to 6; not being abstinent at the Week 12 visit; not abstinent or not self-reported abstinent during the Week 16 to Week 24 follow-up period. (During the follow-up period (Weeks 16 - 24) up to a total of 5 cigarettes could have been smoked.)

    Measured: Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2020
  2. Study start13 Oct 2020
  3. Primary completion23 Dec 2021
  4. Study completion23 Dec 2021

Resources

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
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
810 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04576949
Sponsor's protocol ID
ACH-CYT-03
Acronym
ORCA-2
Status last verified
Dec 2025
First submitted
25 Sep 2020
Last updated
15 Jan 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Prochaska J, Rubinstein M, Perdok R, Blumenstein B, Jacobs C. Cytisinicline for smoking cessation in individuals with self-reported COPD: a post hoc analysis of the ORCA-2 and ORCA-3 trials. Thorax. 2026 Jan 15;81(2):164-169. doi: 10.1136/thorax-2025-223880.

    PubMed 40962497

  • Rigotti NA, Benowitz NL, Prochaska J, Leischow S, Nides M, Blumenstein B, Clarke A, Cain D, Jacobs C. Cytisinicline for Smoking Cessation: A Randomized Clinical Trial. JAMA. 2023 Jul 11;330(2):152-160. doi: 10.1001/jama.2023.10042.

    PubMed 37432430

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Cytisinicline and Behavioral support in people with Smoking Cessation, run by Achieve Life Sciences at 17 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 8 inclusion and 20 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 15 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 14 Nov 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Percentage of Participants With Smoking Abstinence From Weeks 3 to Week 6 (time frame: Weeks 3 to 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04576949, which also lists 2 linked publications.

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 15 Jan 2026.

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