Adaptive Use of Nicotine Substitution to Maintain Smoking Reduction/Abstinence in Nicotine Responders

To determine whether smokers who initially respond (within 2 weeks) to nicotine products (including nicotine replacement therapy, e-cigarettes, nicotine pouches) by reducing their smoking by ≥50% can be successfully maintained on use of these noncombustible nicotine alternatives to cigarettes for 6 months, and whether this results in sustained smoking reduction/abstinence.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Harm Reduction
• Intervention / Treatment: Drug: Nicoderm; Drug: Nicorette 4Mg Chewing Gum; Drug: Nicorette Lozenge Product; Other: NJOY e-cigarette; Other: on!

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28262
      • Rose Research Center
    • Raleigh, North Carolina, United States, 27617
      • Rose Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy, adult smoker of combustible cigarettes.
• Age 22 to 65 years at time of screening (verified by government issued ID).
• Smoke cigarettes for ≥12 months prior to screening.
• Currently smokes at least 10 tobacco cigarettes per day.
• Screening eCO ≥ 10 ppm.
• Voluntarily provides consent for participation by signing the informed consent form (ICF).
• Willing and able to comply with study requirements.

Exclusion Criteria:

• Unable to read, speak or understand English
• Has a history or presence of clinically significant medical or psychiatric disease, or any other condition that would in the PI's judgement jeopardize the safety of the participant, impair the participant's ability to comply with study procedures, or impact the validity of the study results.
• Has used nicotine-containing e-cigarettes (or vapes) or any nicotine replacement therapy (nicotine patch, nicotine gum, nicotine spray, nicotine inhaler, nicotine lozenge) or prescription smoking cessation medications, including, but not limited to, varenicline (Chantix*) or bupropion (Zyban®) within the past 30 days.

If female, participant is pregnant, nursing, or intends to become pregnant during the time period from screening through the end of study.

• Has participated in a research study about tobacco products or ENDS within the past 30 days.
• Has participated in a smoking cessation or nicotine switching research study in the past year.
• Smokes or vapes cannabis more than once a week.
• Cannabis Use Disorder Identification Test-Revised (CUDIT-R) score of 8 or greater.
• Heterosexually active participants of Childbearing Potential (not sterilized by tubal ligation, oophorectomy, hysterectomy, or other surgical methods, or post-menopausal) that do not agree to practice medically appropriate methods of birth control (or remain abstinent) during the course of the trial. Medically acceptable methods of birth control include: vasectomy, vaginal diaphragm with spermicide, intrauterine device, hormonal birth control (oral, injected, or implanted), condom with spermicide, or sponge with spermicide.
• Subgroup enrollment is complete.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotine Non-Responders; Participants that were not successful in reducing their expired carbon monoxide by the end of week 2 will not continue in the study.	Drug: Nicoderm; Depending on responder status and group assignment the maximum amount of time nicotine patches will be used is 24 weeks. The final four weeks of nicotine patch treatment will comprise 2 weeks of 14 mg patches and two weeks of 7 mg patches.; Other Names: Nicotine Patch; Drug: Nicorette 4Mg Chewing Gum; 4mg Nicorette gum (flavors - cinnamon surge, fruit chill, and mint); as needed maximum usage 24 weeks.; Other Names: Nicotine gum; Drug: Nicorette Lozenge Product; 4mg Nicorette mint lozenge; as needed maximum usage 24 weeks.; Other Names: Nicotine lozenge; Other: NJOY e-cigarette; Each NJOY Classic Tobacco and Menthol pod is pre-filled with 1.9 mL of e-liquid with 5% nicotine (by weight); as needed maximum usage 24 weeks.; Other: on!; 4mg on! Nicotine Pouch (flavors - Berry, Mint, and Original); as needed for maximum usage 24 weeks.; Other Names: Nicotine pouch
Experimental: Nicotine Responders - Group 1; Participants that were successful in reducing their expired carbon monoxide by the end of week 2 will be randomized to continued use of their choice of nicotine products for an additional 10 weeks (12-week total treatment period).	Drug: Nicoderm; Depending on responder status and group assignment the maximum amount of time nicotine patches will be used is 24 weeks. The final four weeks of nicotine patch treatment will comprise 2 weeks of 14 mg patches and two weeks of 7 mg patches.; Other Names: Nicotine Patch; Drug: Nicorette 4Mg Chewing Gum; 4mg Nicorette gum (flavors - cinnamon surge, fruit chill, and mint); as needed maximum usage 24 weeks.; Other Names: Nicotine gum; Drug: Nicorette Lozenge Product; 4mg Nicorette mint lozenge; as needed maximum usage 24 weeks.; Other Names: Nicotine lozenge; Other: NJOY e-cigarette; Each NJOY Classic Tobacco and Menthol pod is pre-filled with 1.9 mL of e-liquid with 5% nicotine (by weight); as needed maximum usage 24 weeks.; Other: on!; 4mg on! Nicotine Pouch (flavors - Berry, Mint, and Original); as needed for maximum usage 24 weeks.; Other Names: Nicotine pouch
Experimental: Nicotine Responders - Group 2; Participants that were successful in reducing their expired carbon monoxide by the end of week 2 will be randomized to continued use of their choice of nicotine products for an additional 22 weeks (24-week total treatment period).	Drug: Nicoderm; Depending on responder status and group assignment the maximum amount of time nicotine patches will be used is 24 weeks. The final four weeks of nicotine patch treatment will comprise 2 weeks of 14 mg patches and two weeks of 7 mg patches.; Other Names: Nicotine Patch; Drug: Nicorette 4Mg Chewing Gum; 4mg Nicorette gum (flavors - cinnamon surge, fruit chill, and mint); as needed maximum usage 24 weeks.; Other Names: Nicotine gum; Drug: Nicorette Lozenge Product; 4mg Nicorette mint lozenge; as needed maximum usage 24 weeks.; Other Names: Nicotine lozenge; Other: NJOY e-cigarette; Each NJOY Classic Tobacco and Menthol pod is pre-filled with 1.9 mL of e-liquid with 5% nicotine (by weight); as needed maximum usage 24 weeks.; Other: on!; 4mg on! Nicotine Pouch (flavors - Berry, Mint, and Original); as needed for maximum usage 24 weeks.; Other Names: Nicotine pouch

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Smoking abstinence - CO	To determine whether maintained use of nicotine products can help sustain smoking abstinence rates for early responders. An expired air CO reading of ≤ 5 ppm at 24 weeks.	Week 12 and Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Smoking abstinence - Self report of no smoking	Percent smoking abstinence at 12 weeks and 24 weeks, defined on an intent-to-treat basis as a self-report of no-smoking for the prior 7 days	Week 12 and Week 24
Reduction in Expired Air CO	Percent of participants achieving a 50% reduction in expired air CO at 12 weeks and 24 weeks relative to baseline.	Week 12 and Week 24
Usage of Nicotine Products	Self-reported usage of nicotine products.	Week 1 through Week 24, Week 36
Saliva Cotinine Concentrations	Saliva cotinine concentrations reflective of nicotine product usage in smoking-abstinent individuals.	Week 12, Week 24, Week 36

Collaborators and Investigators

• Sponsor: Rose Research Center, LLC
• Collaborators: Global Action to End Smoking

Study record dates

Study Major Dates

• Study Start (Actual): August 29, 2024
• Primary Completion (Actual): December 9, 2025
• Study Completion (Actual): December 9, 2025

Study Registration Dates

• First Submitted: August 9, 2024
• First Submitted That Met QC Criteria: August 12, 2024
• First Posted (Actual): August 15, 2024

Study Record Updates

• Last Update Posted (Actual): February 6, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavior; Health Behavior; Smoking Cessation; Harm Reduction; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Therapeutics; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Carbohydrates; Alkaloids; Polymers; Macromolecular Substances; Polysaccharides; Biological Products; Complex Mixtures; Biopolymers; Plant Gums; Plant Exudates; Candy; Solanaceous Alkaloids; Nicotine; Chewing Gum; Tobacco Use Cessation Devices; Nicotine Chewing Gum
• Other Study ID Numbers: ATS2

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No