A Second Study of Cytisinicline for Smoking Cessation in Adult Smokers

NCT ID: NCT05206370

Last Updated: 2026-01-14

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

792 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-01-20

Study Completion Date

2023-03-21

Brief Summary

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

Detailed Description

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Conditions

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Smoking Cessation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo + Behavioral Support

One placebo tablet orally (PO) three times daily (TID) for 12 weeks plus behavioral support

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

film-coated oral tablets containing matched placebo

Behavioral support

Intervention Type BEHAVIORAL

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.

6-Week Cytisinicline + 6-Week Placebo + Behavioral Support

One cytisinicline tablet PO TID for 6 weeks followed by one placebo tablet PO TID for 6 weeks plus behavioral support

Group Type EXPERIMENTAL

Cytisinicline

Intervention Type DRUG

film-coated oral tablets containing 3 mg cytisinicline

Placebo

Intervention Type DRUG

film-coated oral tablets containing matched placebo

Behavioral support

Intervention Type BEHAVIORAL

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.

12-Week Cytisinicline + Behavioral Support

One cytisinicline tablet PO TID for 12 weeks plus behavioral support

Group Type EXPERIMENTAL

Cytisinicline

Intervention Type DRUG

film-coated oral tablets containing 3 mg cytisinicline

Behavioral support

Intervention Type BEHAVIORAL

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.

Interventions

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Cytisinicline

film-coated oral tablets containing 3 mg cytisinicline

Intervention Type DRUG

Placebo

film-coated oral tablets containing matched placebo

Intervention Type DRUG

Behavioral support

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.

Intervention Type BEHAVIORAL

Other Intervention Names

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Cytisine

Eligibility Criteria

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Inclusion Criteria

1. Male or female subjects, age ≥ 18 years.
2. 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.
3. Expired air carbon monoxide (CO) ≥ 10 ppm.
4. Failed at least one previous attempt to stop smoking with or without therapeutic support.
5. Willing to initiate study treatment on the day after randomization and set a quit date within 5-7 days of starting treatment.
6. Willing to actively participate in the study's smoking cessation behavioral support provided throughout the study.
7. Able to fully understand all study requirements, willing to participate, and comply with dosing schedule.
8. Sign the Informed Consent Form.

Exclusion Criteria

1. More than 1 study participant in same household during the 12-week treatment period.
2. Previous cytisinicline treatment in a prior clinical study or any other cytisine usage.
3. Known hypersensitivity to cytisinicline or any of the excipients.
4. Positive urinary drugs of abuse screen, determined within 28 days before the first dose of cytisinicline.
5. Clinically significant abnormal serum chemistry or hematology values within 28 days of randomization (ie, requiring treatment or monitoring).
6. Clinically significant abnormalities in 12-lead ECG determined after minimum of 5 minutes in supine position within 28 days of randomization (ie, requiring treatment or further assessment).
7. Recent history (within 3 months) of acute myocardial infarction, unstable angina, stroke, cerebrovascular incident, or hospitalization for congestive heart failure.
8. Current uncontrolled hypertension (blood pressure ≥160/100 mmHg).
9. Currently psychotic or having had a psychotic event within 3 months. If any subject becomes psychotic during the study, they must be removed from treatment and/or additional study visits.
10. Currently having suicidal ideation or risk for suicide ("Yes" to either question 4 or question 5 OR "Yes" to any suicidal behavior question on the Columbia Suicide Severity Rating Scale \[C-SSRS\] with clear suicidal intent or previous attempt).
11. Current symptoms of moderate to severe depression (depression score ≥11on the HADS).
12. Renal impairment defined as a creatinine clearance (CrCl) \<60 mL/min (estimated with the Cockroft-Gault equation).
13. Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 x the upper limit of normal (ULN).
14. Women who are pregnant or breast-feeding.
15. Male or female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study treatment period.
16. Participation in a clinical study with an investigational drug in the 4 weeks prior to randomization.
17. 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.
18. 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.
19. Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Achieve Life Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Daniel Cain, Vice-President Clinical Research

Role: STUDY_DIRECTOR

Achieve Life Sciences, Inc.

Locations

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Accel Research Sites - DeLand Clinical Research Unit

DeLand, Florida, United States

Site Status

Alliance for Multispecialty Research, LLC

Fort Myers, Florida, United States

Site Status

Jacksonville Center for Clinical Research

Jacksonville, Florida, United States

Site Status

Affinity Health Corp

Oak Brook, Illinois, United States

Site Status

MediSphere Medical Research Center, LLC

Evansville, Indiana, United States

Site Status

Global Medical Institutes LLC; Princeton Medical Institute

Princeton, New Jersey, United States

Site Status

Trial Management Associates, LLC

Wilmington, North Carolina, United States

Site Status

Velocity Clinical Research, Inc.

Cleveland, Ohio, United States

Site Status

Aventiv Research Inc

Columbus, Ohio, United States

Site Status

Intend Research

Norman, Oklahoma, United States

Site Status

Clinical Research Associates, Inc.

Nashville, Tennessee, United States

Site Status

Health Research of Hampton Toads, Inc

Newport News, Virginia, United States

Site Status

Countries

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United States

References

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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. 2025 Sep 17:thorax-2025-223880. doi: 10.1136/thorax-2025-223880. Online ahead of print.

Reference Type DERIVED
PMID: 40962497 (View on PubMed)

Rigotti NA, Benowitz NL, Prochaska JJ, Rubinstein M, Clarke A, Blumenstein B, Cain DF, Jacobs C. Cytisinicline for Smoking Cessation: The ORCA Phase 3 Replication Randomized Clinical Trial. JAMA Intern Med. 2025 Jun 1;185(6):648-655. doi: 10.1001/jamainternmed.2025.0628.

Reference Type DERIVED
PMID: 40257755 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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ACH-CYT-04

Identifier Type: -

Identifier Source: org_study_id

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