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

Official title

A Multicenter, Double-blind, Randomized, Placebo-controlled Phase 3 Trial Evaluating the Efficacy and Safety of Cytisinicline for Vaping Cessation in Adults Using Nicotine-Containing E Cigarettes

Overview

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).

Interventions

• Drug Cytisinicline
  Tablet, 3 times a day (TID), 12 weeks
• Drug Placebo
  Tablet, 3 times a day (TID), 12 weeks
• Behavioral Behavioral Support
  16 behavioral support sessions, starting prior to randomization and through Week 12, 3 additional sessions during the follow-up period.

Primary outcome measures

• Primary Efficacy Objective [Time frame: Randomization to Week 24 follow-up visit]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Positive urinary drugs of abuse screen determined within 28 days before the first dose of study drug. (Note: Although THC is part of the standard drug screen, it is not necessarily exclusionary. Refer to exclusion criteria #2).
• 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.
• Recent history or symptoms (within 4 weeks of randomization) of unstable respiratory disease (eg, pneumonia, product-use associated lung injury or EVALI, etc).
• Women who are pregnant or breast-feeding.
• Female subjects of childbearing potential who do not agree to use acceptable methods of birth control during the study. Acceptable methods of birth control include:
• True abstinence: When this is in line with the preferred and usual lifestyle of the subject. \[Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception\].
• Barrier methods:
• diaphragm
• cervical cap
• contraceptive sponge
• intrauterine device (IUD)
• double barrier method (condom with spermicide)
• Hormonal methods:
• Oral contraceptives
• Vaginal ring such as NuvaRing
• Skin patch such as Xulane
• Injection such as Depro-Provera
• Implantable rod such as Nexplanon
• Intrauterine device (IUD)
• Participation in a clinical study with an investigational drug or biologic in the 4 weeks prior to study randomization.
• Use of any smoking cessation medications (bupropion, varenicline, nortriptyline, or any nicotine replacement therapy \[NRT\]) in the 4 weeks prior to study randomization or planned use of these or other nicotine replacement medications during the study.
• Any planned use during the study of combustible cigarettes or other nicotine-containing, non-vaping products (eg, pipe tobacco, cigars, snuff, smokeless tobacco, hookah, ZYN pouches, etc).
• Any other reason that the investigator views the subject should not participate or would be unable to fulfill the requirements for the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07392125 · ACH-CYT-12

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗