Abuse Liability for Five Modern Oral Nicotine Products

NCT07132814 | Recruiting

• 1 other identifier: CSD252401
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a two-site, open-label, randomized, 4-way (2 arm) cross-over study designed to evaluate elements of abuse liability (AL) including subjective effects and physiological measures (pharmacodynamics \[PD\]) and plasma nicotine uptake (pharmacokinetics \[PK\]) during and following ad libitum use of the study investigational products (IPs) by generally healthy smokers

Conditions

Smoking; Smoking Behaviors; Tobacco Use; Tobacco Smoking

Outcome Measures

Primary Outcomes (2)

• AUECPL 5-240

  area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use area under the effect curve (AUEC) for PL (VAS score-versus-time) from 5 minutes to 240 minutes after the start of IP use.

  5 minutes to 240 minutes

• Emax PL

  maximum effect (maximum PL VAS score after the start of IP use)

  240 minutes

Study Arms (2)

Arm 1

EXPERIMENTAL

Enrolled subjects will be randomized to one of four product use sequences, such that one of the four IPs (A, B, C, D) will be used in each of the four test sessions.

Other: Product A; Other: Product B; Other: Product C; Other: Product D

Arm 2

EXPERIMENTAL

Enrolled subjects will be randomized to one of four product use sequences, such that one of the four IPs (A, E, F, N) will be used in each of the four test sessions.

Other: Product A; Other: Product E; Other: Product F; Other: Product N

Interventions

Product A OTHER

Usual Brand (UB) filtered, non-menthol or menthol combustible cigarette

Arm 1; Arm 2

Product B OTHER

8 mg nicotine oral product

Arm 1

Product C OTHER

12 mg nicotine oral product

Arm 1

Product D OTHER

6 mg nicotine oral product

Arm 1

Product E OTHER

8 mg nicotine oral product

Arm 2

Product F OTHER

8 mg nicotine oral product

Arm 2

Product N OTHER

Nicorette® White Ice Mint 4 mg nicotine polacrilex gum

Arm 2

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Able to read, understand, and willing to sign an informed consent form (ICF) and complete questionnaires written in English.
• Generally healthy males or females, 21 to 60 years of age, inclusive, at the time of consent.
• Smokes combustible, filtered, non-menthol or menthol cigarettes, 83 mm to 100 mm in length as primary source of tobacco.
• Smokes an average of at least 10 cigarettes per day (CPD) and inhales the smoke, for at least 6 months prior to Screening. Brief periods of abstinence due to illness, quit attempt (prior to 30 days of Screening), or clinical study participation (prior to 30 days of Screening) will be allowed at the discretion of an investigator.
• Smokers who also use ST products (e.g., moist snuff, snus, modern oral), and have used ST within 30 days prior to screening, will be enrolled.
• Agrees to smoke the same UB cigarette throughout the study period. The UB cigarette is defined as the reported cigarette brand and style currently smoked most frequently by the participant.
• Expired breath carbon monoxide (ECO) level is ≥ 10 ppm and ≤ 100 ppm at Screening.
• Positive urine cotinine test (e.g., \>200 ng/mL) via dipstick at Screening.
• Response at Screening to the Fagerström Test for Nicotine Dependence (FTND) Question 1 ("How soon after you wake up do you smoke your first cigarette?") is either "Within 5 minutes" or "6-30 minutes" .
• Willing to use the UB cigarette, Study IPs, and Nicorette® nicotine gum (Arm 2 only) during the study period.
• Willing to abstain from tobacco and nicotine use for at least 12 hours prior to the start of each of four Test Sessions.
• Females must be willing to use a form of contraception acceptable to an investigator from the time of signing the ICF until End-of-Study.
• Examples of acceptable means of birth control are, but not limited to:
• Surgical sterilization (hysterectomy, bilateral tubal ligation/occlusion, bilateral oophorectomy, bilateral salpingectomy);
• physical barrier method (e.g., condom, diaphragm/sponge/cervical cap) with spermicide;

You may not qualify if:

• Allergic to or cannot tolerate mint or wintergreen flavoring agents.
• Individuals or their family members that have ongoing litigation with tobacco company(ies).
• Have used electronic nicotine delivery system (e.g., Vuse Alto, JUUL) or tobacco heating device (e.g., iQOS) within the last 30 days prior to screening.
• Presence of clinically significant uncontrolled cardiovascular, pulmonary, renal, hepatic, endocrine, gastrointestinal, psychiatric, hematological, neurological disease, or any other concurrent disease or medical condition that, in the opinion of an investigator, makes the study participant unsuitable to participate in this clinical study.
• History, presence of, or clinical laboratory test results indicating diabetes.
• Scheduled treatment for asthma currently or within the past consecutive 12 months prior to the Screening Visit. As-needed treatment, such as inhalers, may be included at an investigator discretion.
• History or presence of bleeding or clotting disorders.
• Any history of cancer, except for primary cancers of skin such as localized basal cell/squamous cell carcinoma that has been surgically and/or cryogenically removed.
• Systolic blood pressure of \> 160 mmHg or a diastolic blood pressure of \> 95 mmHg, measured after being seated for five minutes at Screening or at check-in Day -1.
• Weight of ≤ 50.0 kg at screening or at check-in.
• Hemoglobin level is \< 12.5 g/dL for females or \< 13.0 g/dL for males at Screening.
• Females who have a positive pregnancy test, are pregnant, breastfeeding, or intend to become pregnant during the course of the study.
• Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HbsAg), or hepatitis C virus (HCV).
• Use of any medication or substance that aids in smoking cessation, including but not limited to any NRT (e.g., nicotine gum, lozenge, patch), varenicline (Chantix®), bupropion (Wellbutrin®, Zyban®), or lobelia extract within (≤) 30 days prior to signing the informed consent.
• Postpones a decision to quit using tobacco- or nicotine-containing products in order to participate in this study or self-reports a previous quit attempt within (≤) 30 days prior to signing the informed consent.

Sponsors & Collaborators

• RAI Services Company: lead

Study Sites (1)

Dr. Vince Clinical Research

Overland Park, Kansas, 66212, United States

RECRUITING

MeSH Terms

Conditions

Smoking; Tobacco Use; Tobacco Smoking

Interventions

HTR3D protein, human

Condition Hierarchy (Ancestors)

Behavior

Study Officials

• Brian Keyser

  Reynolds American

  STUDY DIRECTOR

Central Study Contacts

John Darnell

CONTACT

3367410386; darnelj2@rjrt.com

Kristen Prevette

CONTACT

3367411873; prevetk1@rjrt.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 20, 2025
• Study Start: December 15, 2025
• Primary Completion: April 15, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)