A Second Study of Cytisinicline for Smoking Cessation in Adult Smokers

NCT05206370 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ACH-CYT-04
• Study Type: interventional
• Target: 792
• Locations: 1 country
• Sites: 12

Brief Summary

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.

Conditions

Smoking Cessation

Outcome Measures

Primary Outcomes (2)

• 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).

  Weeks 3 to 6

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

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

  Weeks 9 to 12

Secondary Outcomes (3)

• Percentage of Participants With Continuous Smoking Abstinence From Week 3 to Week 24

  Week 3 to Week 24

• Percentage of Participants With Continuous Smoking Abstinence From Week 9 to Week 24

  Week 9 to Week 24

• Percentage of Participants Taking Cytisinicline Who Are Relapse-Free at Week 24

  Week 24

Study Arms (3)

Placebo + Behavioral Support

PLACEBO COMPARATOR

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

Drug: Placebo; Behavioral: Behavioral support

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

EXPERIMENTAL

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

Drug: Cytisinicline; Drug: Placebo; Behavioral: Behavioral support

12-Week Cytisinicline + Behavioral Support

EXPERIMENTAL

One cytisinicline tablet PO TID for 12 weeks plus behavioral support

Drug: Cytisinicline; Behavioral: Behavioral support

Interventions

Cytisinicline DRUG

film-coated oral tablets containing 3 mg cytisinicline

Also known as: Cytisine

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

Placebo DRUG

film-coated oral tablets containing matched placebo

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

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 all study requirements, willing to participate, and comply with dosing schedule.
• Sign the Informed Consent Form.

You may not qualify if:

• More than 1 study participant in same household during the 12-week treatment period.
• 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 ECG determined after minimum of 5 minutes in supine position within 28 days of randomization (ie, requiring treatment or further assessment).
• 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).
• 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.
• 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).
• Current symptoms of moderate to severe depression (depression score ≥11on the HADS).
• 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.

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (12)

Accel Research Sites - DeLand Clinical Research Unit

DeLand, Florida, 32720, United States

Location

Alliance for Multispecialty Research, LLC

Fort Myers, Florida, 33912, United States

Location

Jacksonville Center for Clinical Research

Jacksonville, Florida, 32216, United States

Location

Affinity Health Corp

Oak Brook, Illinois, 60523, United States

Location

MediSphere Medical Research Center, LLC

Evansville, Indiana, 47714, United States

Location

Global Medical Institutes LLC; Princeton Medical Institute

Princeton, New Jersey, 08540, United States

Location

Trial Management Associates, LLC

Wilmington, North Carolina, 28403, United States

Location

Velocity Clinical Research, Inc.

Cleveland, Ohio, 44122, United States

Location

Aventiv Research Inc

Columbus, Ohio, 43212, United States

Location

Intend Research

Norman, Oklahoma, 73069, United States

Location

Clinical Research Associates, Inc.

Nashville, Tennessee, 37203, United States

Location

Health Research of Hampton Toads, Inc

Newport News, Virginia, 23606, United States

Location

Related Publications (2)

• 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.

  PMID: 40962497 DERIVED

• 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.

  PMID: 40257755 DERIVED

MeSH Terms

Conditions

Smoking Cessation

Interventions

cytisine; Behavior Therapy

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Roxann Becco, Sr. Director, Clinical Operations
• Organization: Achieve Life Sciences

rbecco@achievelifesciences.com

425-686-1500

Study Officials

• Daniel Cain, Vice-President Clinical Research

  Achieve Life Sciences, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2022
• First Posted: January 25, 2022
• Study Start: January 20, 2022
• Primary Completion: March 21, 2023
• Study Completion: March 21, 2023
• Last Updated: January 14, 2026
• Results First Posted: January 14, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (12)