A Study of Cytisinicline for Smoking Cessation in Adult Smokers

NCT04576949 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: ACH-CYT-03
• Study Type: interventional
• Target: 810
• Locations: 1 country
• Sites: 17

Brief 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.

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 6 to Week 24

  Week 6 to Week 24

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

  Week 12 to Week 24

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

  Week 24

Study Arms (3)

Placebo + Behavioral Support

PLACEBO COMPARATOR

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

Drug: Placebo; Behavioral: Behavioral support

Cytisinicline + Placebo + Behavioral Support

EXPERIMENTAL

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

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

Cytisinicline + Behavioral Support

EXPERIMENTAL

one cytisinicline tablet PO TID plus behavioral support for 12 weeks

Drug: Cytisinicline; Behavioral: Behavioral support

Interventions

Cytisinicline DRUG

film-coated oral tablets containing 3 mg cytisinicline

Also known as: Cytisine

Cytisinicline + Behavioral Support; Cytisinicline + Placebo + Behavioral Support

Placebo DRUG

film-coated oral tablets containing matched placebo

Cytisinicline + 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.

Cytisinicline + Behavioral Support; Cytisinicline + 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 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.
• 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).
• 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.

Sponsors & Collaborators

• Achieve Life Sciences: lead

Study Sites (17)

Alliance for Multispecialty Research, LLC.

Mobile, Alabama, 36608, United States

Location

Arizona State University

Phoenix, Arizona, 85044, United States

Location

Alliance for Multispecialty Research, LLC

Coral Gables, Florida, 33134, United States

Location

Clinical Research Atlanta

Atlanta, Georgia, 30281, United States

Location

MediSphere Medical Research Center, LLC

Evansville, Indiana, 47714, United States

Location

Alliance for Multispecialty Research, LLC

Wichita, Kansas, 67207, United States

Location

AMR Lexington

Lexington, Kentucky, 40509, United States

Location

Alliance for Multispecialty Research, LLC

New Orleans, Louisiana, 70119, United States

Location

Massachusetts General Hospital - Clinical Genetic Research Facility

Boston, Massachusetts, 02114, United States

Location

Alliance for Multispecialty Research, LLC

Kansas City, Missouri, 64114, United States

Location

Alliance for Multispecialty Research, LLC

Las Vegas, Nevada, 89119, United States

Location

Rochester Clinical Research, Inc.

Rochester, New York, 14609, United States

Location

M3 Wake Research, Inc.

Raleigh, North Carolina, 27612, United States

Location

Coastal Carolina Research Center, Inc.

Mt. Pleasant, South Carolina, 29464, United States

Location

Alliance for Multispecialty Research, LLC.

Knoxville, Tennessee, 37920, United States

Location

FutureSearch Trials of Dallas, LP

Dallas, Texas, 75231, United States

Location

Alliance for Multispecialty Research, LLC

Norfolk, Virginia, 23502, 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 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.

  PMID: 37432430 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: Daniel Cain, Vice President, Clinical Research
• Organization: Achieve Life Sciences

dcain@achievelifesciences.com

425.686.1546

Study Officials

• Nancy Rigotti, MD

  Mass General/Harvard Medical School

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

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

Study Record Dates

• First Submitted: September 25, 2020
• First Posted: October 6, 2020
• Study Start: October 13, 2020
• Primary Completion: December 23, 2021
• Study Completion: December 23, 2021
• Last Updated: January 15, 2026
• Results First Posted: November 14, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)