Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline for Vaping Cessation in Adults Using Nicotine-Containing E Cigarettes

NCT07392125 | Not Yet Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: ACH-CYT-12
• Study Type: interventional
• Target: 800
• Locations: 0 countries
• Sites: N/A

Brief Summary

This will be a multi-center, double-blind, randomized, placebo-controlled, Phase 3 study conducted in male or female adults who are daily nicotine e-cigarette users only. A total of approximately 800 subjects will be randomly assigned (1:1) to one of two Arms:

• Arm B, 12 weeks cytisinicline + behavior support: N=400 or
• Arm A, 12 weeks of placebo+ behavior support: N=400) The primary objective is to assess whether subjects randomized to Arm B (3 mg cytisinicline TID for 12 weeks plus behavioral support) have a higher probability of nicotine vaping cessation from Week 9 to Week 12 as compared to subjects randomized to Arm A (placebo TID for 12 weeks plus behavioral support).

Conditions

Vaping Cessation

Keywords

vaping cessation

Outcome Measures

Primary Outcomes (1)

• Primary Efficacy Objective

  Assess whether subjects randomized to Arm B (3 mg cytisinicline TID for 12 weeks plus behavioral support) have a higher probability of nicotine vaping cessation from Week 9 to Week 12 post-randomization as compared to subjects randomized to Arm A (placebo TID for 12 weeks plus behavioral support). Successful vaping cessation is defined as weekly vaping abstinence during the last 4 weeks of the 12-week treatment period (Week 9 through Week 12) using quantitative cotinine levels at \<10 ng/mL for biochemical verification and subject's self-report of no vaping using a daily electronic diary

  Randomization to Week 24 follow-up visit

Study Arms (2)

Arm A

PLACEBO COMPARATOR

12 weeks of placebo + behavioral support; 400 subjects

Drug: Placebo; Behavioral: Behavioral Support

Arm B

ACTIVE COMPARATOR

12 weeks cytisinicline + behavioral support; 400 subjects

Drug: Cytisinicline; Behavioral: Behavioral Support

Interventions

Cytisinicline DRUG

Tablet, 3 times a day (TID), 12 weeks

Also known as: cytisine

Arm B

Placebo DRUG

Tablet, 3 times a day (TID), 12 weeks

Arm A

Behavioral Support BEHAVIORAL

16 behavioral support sessions, starting prior to randomization and through Week 12, 3 additional sessions during the follow-up period.

Arm A; Arm B

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.
• Test positive for cotinine using a point-of-care Oral Fluid Screening Device (OFD) with positive detection at ≥30 ng/mL cotinine.
• Current daily nicotine-containing electronic cigarette usage as recorded in a screening diary for at least 7 consecutive days. Willing to bring the e-cigarette or nicotine device used to the clinical site so that the specific product type, flavor, and nicotine level can be documented.
• Failed at least one previous attempt to stop vaping with or without therapeutic support.
• Willing to initiate study treatment on the day after randomization and set a quit date within Day 7 and Day 14.
• Willing to actively participate in the study's vaping 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:

• Currently smoking or having smoked within 3 months prior to study randomization, any combustible cigarettes, other combustible tobacco products or non-combustible tobacco products such as heat not burn products or nicotine pouches (ie, dual users).
• Currently smoking/vaping cannabis or having smoked or vaped cannabis within 4 weeks (28 days) prior to study randomization or planned use while on study. Other methods of cannabis consumption, eg, edibles, tinctures, capsules, topicals, etc. are allowed.
• Expired Carbon Monoxide (CO) levels ≥6 ppm, indicating recent combustible tobacco or cannabis smoking.
• A score of 0-3 on the Penn State e-Cigarette Dependence Index indicating no dependence.
• More than 1 study subject in same household during the study treatment period.
• Known hypersensitivity to any of the excipients, previous cytisinicline treatment in a prior clinical study, or any previous use of cytisinicline.
• Clinically significant abnormal serum chemistry or hematology values, as determined by the investigator, within 28 days of randomization.
• Clinically significant abnormalities on screening visit 12-lead ECG, as determined by the investigator, after minimum of 5 minutes in supine position within 28 days of randomization.
• 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 in the 3 months prior to the screening visit. 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 3, 4 or 5 OR YES to any suicidal behavior question on the C-SSRS with clear suicidal intent or suicide attempt within the last 10 years).
• Current symptoms of moderate to severe depression (depression score ≥11 using depression questions on the Hospital Anxiety and Depression Scale \[HADS\] at screening visit).
• Renal impairment defined as a creatinine clearance (CrCl) \<60 mL/min at screening visit (estimated with the Cockroft-Gault equation and reported by the central laboratory).
• Hepatic impairment defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>2.0 x the upper limit of normal (ULN) at screening visit.

Sponsors & Collaborators

• Achieve Life Sciences: lead

MeSH Terms

Interventions

cytisine; Behavior Therapy

Intervention Hierarchy (Ancestors)

Psychotherapy; Behavioral Disciplines and Activities

Study Officials

• Julie Ball

  Achieve Life Sciences, Inc.

  STUDY DIRECTOR

Central Study Contacts

Julie Ball; Vice President, Clinical Operations

CONTACT

425-686-1540; jball@achievelifesciences.com

Roxann Becco; Sr. Director, Clinical Operations

CONTACT

312-288-1187; rbecco@achievelifesciences.com

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 20, 2026
• First Posted: February 6, 2026
• Study Start (Estimated): May 15, 2026
• Primary Completion (Estimated): November 15, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: February 6, 2026

Record last verified: 2026-01